(260 days)
[[K162827](https://510k.innolitics.com/search/K162827)]
Not Found
No
The description focuses on biophysical property measurements and a calculated index, without mentioning AI/ML algorithms for data analysis or interpretation.
No
The device is an in vitro diagnostic (IVD) test that aids in the early detection of sepsis by assessing cellular host response. It does not directly treat or prevent a disease.
Yes
Explanation: The IntelliSep test is described as helping "aid in the early detection of sepsis with organ dysfunction" and provides an "IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis". This directly indicates its use in diagnosing a condition. Furthermore, the text explicitly states, "The IntelliSep test is intended for in vitro diagnostic use."
No
The device description explicitly states that the IntelliSep test is run on the "Cytovale System, a laboratory benchtop analyzer" which is comprised of hardware modules (Sample Preparation Module, Cell Imaging Module, and Imaging Analysis Module). This indicates it is a hardware device with integrated software, not a software-only medical device.
Yes, this device is an IVD (In Vitro Diagnostic).
The document explicitly states in the "Intended Use / Indications for Use" section: "The IntelliSep test is intended for in vitro diagnostic use."
Furthermore, the description of the device and its function aligns with the definition of an IVD:
- It is a test performed on a biological sample (EDTA anticoagulated whole blood).
- It is used to assess a medical condition (sepsis with organ dysfunction).
- It is intended to be used in a laboratory setting by trained personnel.
N/A
Intended Use / Indications for Use
The Cytovale IntelliSep test is a semi-quantitative test that assesses cellular host response via deformability cytometry of leukocyte biophysical properties and is intended for use in conjunction with clinical assessments and laboratory findings to aid in the early detection of sepsis with organ dysfunction manifesting within the first 3 days after testing. It is indicated for use in adult patients with signs and symptoms of infection who present to the Emergency Department. The test is performed on an EDTA anticoagulated whole blood sample.
The IntelliSep test generates an IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis with organ dysfunction manifesting within the first three days after test represents the probability of the clinical syndrome of sepsis and is intended to be used alongside other clinical information and clinical judgement. It does not identify the causative agent of infection and should not be used as to determine the presence of sepsis. The IntelliSep test is intended for in vitro diagnostic use.
Product codes
OUT
Device Description
The Cytovale IntelliSep test is a short turn-around time (STAT) test, producing results in 10 minutes or less, to aid in the early identification of patients at risk for having or developing sepsis within three (3) days of testing. It assesses the state of immune activation in patients with clinical suspicion of infection who present in the Emergency Department (ED).
The IntelliSep test is run on the Cytovale System, a laboratory benchtop analyzer. The Cytovale System is a closed system benchtop analyzer, comprised of three modules: Sample Preparation Module, Cell Imaging Module, and Imaging Analysis Module. Other required and supplied materials include a Barcode scanner, Printer, Sample Preparation Tube, IntelliSep Cartridge, Cytovale Reagent Kit (Nonbiological salt solutions for lysing red blood cells and quenching), and Cytovale Diluent and Cleanse Reagents (Diluent for suspending white blood cells, Cleanse for rinsing the SPM). An IntelliSep Quality Control Kit (two-level, derived from stabilized whole blood) is also used, though quality controls are required but not supplied by Cytovale.
To run a test, the laboratory operator transfers 100 µL of whole blood into the sample preparation tube, which is then placed into the Cytovale System. The system automatically lyses red blood cells, washes the purified leukocytes in a diluent, producing approximately 1mL of prepared sample. The operator then transfers this prepared sample to the IntelliSep cartridge for analysis on the Cytovale System.
A microfluidic deformability cytometry technique is used to measure the biophysical properties of thousands of individual leukocytes in rapid succession. Based on these measurements, the test provides a single score, the IntelliSep Index (ISI), ranging from 0.1-10.0, stratified into three discrete interpretation bands (Band 1, Band 2, Band 3) of sepsis likelihood.
Mentions image processing
Not Found
Mentions AI, DNN, or ML
Not Found
Input Imaging Modality
Not Found
Anatomical Site
Not Found
Indicated Patient Age Range
adult patients (≥ 18 years of age)
Intended User / Care Setting
To be performed by trained laboratory personnel in a clinical or hospital laboratory setting
Description of the training set, sample size, data source, and annotation protocol
Not Found
Description of the test set, sample size, data source, and annotation protocol
Cytovale conducted a blinded, prospective, observational, multicenter cohort study at five hospitals at four geographically dispersed sites comprised of both academic and community hospital Emergency Departments (EDs) in the United States.
599 subjects were enrolled in the study and 572 evaluable subjects were included in the primary analyses. Subjects spanned across ranges of age (18 to 103 years of age; 33% of subjects ≥ 65), race (62% white, 30% Black or African American, 2% Asian, and 6% other), ethnicity (6% Hispanic), and sex (44% female). They encompassed those with common comorbidities, including but not limited to diabetes, hypertension, chronic kidney disease, cancer, and obesity. Infection sources affecting or originating from all major organ systems (i.e., respiratory, genitourinary, skin, gastrointestinal, cardiovascular system, central nervous system, and bone) were represented in the study. Additionally, 9% of the subjects enrolled in the study were SARS-CoV-2 positive.
The IntelliSep test was performed on an EDTA anticoagulated whole blood sample obtained within 4 hours of the first recorded vital sign (triage). Subsequently, subjects were followed with retrospective chart review for outcome information. Subjects received standard of care and treating physicians were unaware of study enrollment and IntelliSep test results.
The performance of the IntelliSep test was evaluated by comparison to non-reference retrospective physician adjudication. All subjects were adjudicated by two qualified physicians following the consensus definitions for Sepsis-2 and Sepsis-3. Discordant results were arbitrated through a committee meeting that included a third physician. The adjudication process determined each case to be 'Sepsis' with 'unanimous', 'consensus' or 'forced' determinations for both Sepsis-3 consensus definitions. All study personnel, including study adjudicators, were blinded to the IntelliSep test results.
A multi-tiered adjudication process was utilized to standardize and reduce the inherent subjectivity and variability of using a non-reference comparator. Approximately 30 days after the subject was enrolled, a chart review, using a structured case report form (CRF), was performed. All sites were required to extract the same information to enable adjudication based on the case report form. The information captured included demographics, laboratory results, vital signs, past medical history, hospital encounter information, infectious disease information, medications, and discharge disposition. Additionally, objective evidence of infection (present at the time of ED presentation) and organ dysfunction (manifesting within 3 days following ED presentation) using the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score was captured. Furthermore, a clinical impression was prepared by designated study-trained physicians that were not involved in the subject's care.
Information obtained from the Demographic and Clinical Case Report Forms, Objective Evaluation, and the clinical impression was then compiled into a case report summary (CRS) and sent to two independent adjudicators. If the two adjudicators agreed in their determination, the case was considered 'unanimous' adjudication. If there was disagreement, the CRS was sent to a third adjudicator and a consensus meeting was held. If all could agree, the case fell under 'consensus' or if following discussion consensus could not be reached, a 'forced' (majority two out of three) adjudication determination was reached. The study independent adjudication committee comprised of physicians with board certification in Medical or Surgical Critical Care (CC), Infectious Diseases (ID), Emergency Medicine (EM) or Internal Medicine (IM) or related fields, from different institutions who were not participating as an Investigator in the Study. Individual cases were assigned to the adjudicators by a third-party vendor, without involvement from Cytovale. Adjudicators were blinded to the identity of the Site Investigators and Medical Monitors.
Summary of Performance Studies (study type, sample size, AUC, MRMC, standalone performance, key results)
Clinical Performance Summary:
Study Type: Blinded, prospective, observational, multicenter cohort study.
Sample Size: 599 subjects enrolled, 572 evaluable subjects included in primary analyses.
Key Results: The prevalence of sepsis, using the forced Sepsis-3 consensus definition adjudication scheme, was 26.6%. A clear relationship was observed between IntelliSep Index (ISI) and the increasing likelihood of having or developing sepsis within 3 days across all approaches to analyzing retrospective physician adjudication results. The probability of sepsis in the three ISI IntelliSep test Interpretation Bands was statistically distinct, defined as non-overlapping 80% confidence intervals between the bands, regardless of the comparator scheme chosen.
The IntelliSep ISI risk stratification score trended upwards with the adjudication determination of sepsis independent of demographic groups (age, sex, race, and ethnicity). Additionally, trends were observed between increasing ISI values across the Interpretation bands and hospital care metrics (e.g., hospital admission, ICU admission and transfer, hospital length of stay, and administration of antibiotics). Note: The study was not designed nor powered to evaluate endpoints with regards to severity of illness or hospital care metrics, and observed trends are observational.
Descriptive (Non-Powered) Analyses:
Study Type: Descriptive non-powered analyses to explore test performance by demographic subgroups.
Key Results: The association of IntelliSep Index (expressed in terms of its Interpretation Bands) with the predictive value of sepsis (an adjudicated non-reference method) using the Sepsis-3 consensus standard definition was examined for demographic subgroups split by age (
§ 866.3215 Device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis.
(a)
Identification. A device to detect and measure non-microbial analyte(s) in human clinical specimens to aid in assessment of patients with suspected sepsis is identified as an in vitro device intended for the detection and qualitative and/or quantitative measurement of one or more non-microbial analytes in human clinical specimens to aid in the assessment of patients with suspected sepsis when used in conjunction with clinical signs and symptoms and other clinical and laboratory findings.(b)
Classification. Class II (special controls). The special controls for this device are:(1) Premarket notification submissions must include the device's detailed Indications for Use statement describing what the device detects and measures, the results provided to the user, whether the measure is qualitative and/or quantitative, the clinical indications for which the test is to be used, and the specific population(s) for which the device use is intended.
(2) Premarket notification submissions must include detailed documentation of the device description, including (as applicable), all device components, software, ancillary reagents required but not provided, explanation of the device principle and methodology, and for molecular devices include detailed documentation of the primer/probe sequence, design, and rationale for sequence selection.
(3) Premarket notification submissions must include detailed documentation of applicable analytical studies, such as, analytical sensitivity (Limit of Detection, Limit of Blank, and Limit of Quantitation), precision, reproducibility, analytical measuring range, interference, cross-reactivity, and specimen stability.
(4) Premarket notification submissions must include detailed documentation of a prospective clinical study or, if appropriate, results from an equivalent sample set. This detailed documentation must include the following information:
(i) Results must demonstrate adequate device performance relative to a well-accepted comparator.
(ii) Clinical sample results must demonstrate consistency of device output throughout the device measuring range likely to be encountered in the Intended Use population.
(iii) Clinical study documentation must include the original study protocol (including predefined statistical analysis plan), study report documenting support for the Indications for Use(s), and results of all statistical analyses.
(5) Premarket notification submissions must include evaluation of the level of the non-microbial analyte in asymptomatic patients with demographic characteristics (
e.g., age, racial, ethnic, and gender distribution) similar to the Intended Use population.(6) As part of the risk management activities performed under 21 CFR 820.30 design controls, you must document an appropriate end user device training program that will be offered as part of your efforts to mitigate the risk of failure to correctly operate the instrument.
(7) A detailed explanation of the interpretation of results and acceptance criteria must be included in the device's 21 CFR 809.10(b)(9) compliant labeling, and a detailed explanation of the interpretation of the limitations of the samples (
e.g., collected on day of diagnosis) must be included in the device's 21 CFR 809.10(b)(10) compliant labeling.
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December 20, 2022
Cytovale Inc. Juliet Carrara Exec. Vice President of Regulatory & Clinical Affairs and Quality Assurance 150 Executive Park Blvd, Suite 4100 San Francisco, California 94134
Re: K220991
Trade/Device Name: IntelliSep test Regulation Number: 21 CFR 866.3215 Regulation Name: Device To Detect And Measure Non-Microbial Analyte(S) In Human Clinical Specimens To Aid In Assessment Of Patients With Suspected Sepsis Regulatory Class: Class II Product Code: OUT Dated: March 31, 2022 Received: April 4, 2022
Dear Juliet Carrara:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
1
statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Image /page/1/Picture/5 description: The image shows a digital signature. The signature is for Bryan M. Grabias and was signed on December 20, 2022, at 13:35:28 -05'00'. The signature indicates that the document has been digitally signed.
Noel Gerald Branch Chief Division of Microbiology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
2
Indications for Use
510(k) Number (if known) K220991
Device Name IntelliSep test
Indications for Use (Describe)
The Cytovale IntelliSep test is a semi-quantitative test that assesses cellular host response via deformability cytometry of leukocyte biophysical properties and is intended for use in conjunction with clinical assessments and laboratory findings to aid in the early detection of sepsis with organ dysfunction manifesting within the first 3 days after testing. It is indicated for use in adult patients with signs and symptoms of infection who present to the Emergency Department. The test is performed on an EDTA anticoagulated whole blood sample.
The IntelliSep test generates an IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis with organ dysfunction manifesting within the first three days after test represents the probability of the clinical syndrome of sepsis and is intended to be used alongside other clinical information and clinical judgement. It does not identify the causative agent of infection and should not be used as to determine the presence of sepsis. The IntelliSep test is intended for in vitro diagnostic use.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
Over-The-Counter Use (21 CFR 801 Subpart C)
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| Name: | Cytovale, Inc. |
|---|---|
| Address: | 150 Executive Park Blvd, Suite 4100, San Francisco, CA 94134 |
| Telephone: | 1-415-417-2188 |
| Contact Person: | Juliet Carrara |
| Email Address: | juliet.carrara@cytovale.com |
1 510(k) Owner / Submitter Information Name
2 Date Summary was Prepared December 19, 2022
3 Device Name and Classification
| Trade Name: | IntelliSep test |
|---|---|
| Instrument Name: | Cytovale System |
| Classification: | Class II (Special Controls) |
| Classification Name: | Device to detect and measure non-microbial analyte(s) in human clinical |
| specimens to aid in assessment of patients with suspected sepsis (21 CFR | |
| 866.3215) | |
| Product Code: | QUT |
| Panel: | 83 - Division of Microbiology Devices |
4 Predicate Device Information
| Predicate Product | 510(k)
Number | Date of
Clearance | Classification | Regulation | Classification
Product Code |
|--------------------------------|------------------|----------------------|--------------------------------|------------|--------------------------------|
| VIDAS B·R·A·H·M·S
PCT (PCT) | K162827 | February 23, 2017 | Class II
(Special Controls) | 866.3215 | PRI |
Table 1: Predicate device information
5 Device Description
The Cytovale IntelliSep test is a short turn-around time (STAT) test, producing results in 10 minutes or less, to aid in the early identification of patients at risk for having or developing sepsis within three (3) days of testing. It assesses the state of immune activation in patients with clinical suspicion of infection who present in the Emergency Department (ED).
The IntelliSep test is run on the Cytovale System, a laboratory benchtop analyzer depicted in Figure
Image /page/3/Figure/13 description: The image shows a Cytovale system, which includes several modules. There is a Sample Preparation Module (SPM), a Cell Imaging Module (CIM), and an Imaging Analysis Module (IAM). The image also shows Cytovale reagents, as well as a printer and barcode scanner.
Figure 1: The Cytorale System is a closed system benchtop andyzer, comprised of three modules: Sample Preparation Module, Cell Imaging Module, and Imaging Analysis Moduled are the Cytorale System Reagent (Cytovale Reagent Kit, Cytovale Diluent, Cytovale Cleanse), Barcode Scanner and Printer (not shown: IntelliSep Cartridge, Sample Preparation Tube),
4
The IntelliSep test requires use of the materials described in Table 2.
| IntelliSep test Materials & Equipment | Description |
|---|---|
| Cytovale System: | |
| (Required and supplied) | |
| • Sample Preparation Module (SPM) | |
| • Cell Imaging Module (CIM) | |
| • Imaging Analysis Module (IAM) | A closed system benchtop analyzer as shown in Figure 1. It |
| is comprised of three modules: Sample Preparation Module, | |
| Cell Imaging Module and Imaging Analysis Module. | |
| Barcode scanner | |
| (Optional and supplied) | Scanner used to automatically enter sample and material |
| identifiers. | |
| Printer | |
| (Optional and supplied) | Printer used to print a hard copy of results. |
| Sample Preparation Tube | |
| (Required and supplied) | A single-use, commercial off-the-shelf test tube used for |
| sample preparation. | |
| IntelliSep Cartridge | |
| (Required and supplied) | Closed system test cartridge which presents the sample for |
| testing in the Cell Imaging Module. | |
| Cytovale Reagent Kit | |
| (Required and supplied) | Nonbiological salt solutions (Reagent A Lysis and Reagent |
| B Quench), for use with the Sample Preparation Module to | |
| lyse red blood cells and quench the lysis reaction. | |
| Cytovale Diluent and Cleanse Reagents | |
| (Required and supplied) | The Diluent solution is used in the Sample Preparation |
| Module to suspend white blood cells for analysis. The | |
| Cleanse is a rinsing solution for the SPM. | |
| IntelliSep Quality Control Kit | |
| (Quality controls are required but not | |
| supplied) | A two-level Quality Control set, derived from stabilized |
| whole blood. | |
| Note: Per 42 CFR 493.1256, quality controls are required for the | |
| IntelliSep test; however, at their discretion, laboratory directors | |
| may develop their own quality control materials or order the | |
| IntelliSep Quality Control Kit. |
Table 2: Materials and equipment required for the IntelliSep test
To run a test, the laboratory operator transfers 100 µL of whole blood into the sample preparation tube which is then placed into the Cytovale System. The system automatically lyses red blood cells, and washes the purified leukocytes in a diluent, producing a total volume of approximately 1mL of prepared sample, which the operator then transfers to the IntelliSep cartridge for analysis on the Cytovale System.
A microfluidic deformability cytometry technique is used to measure the biophysical properties of thousands of individual leukocytes in rapid succession. These properties have been shown to differ in quiescent white blood cell populations when compared to those in septic patients, enabling for rapid assessment of the host response and the likelihood of having or developing sepsis. Based on these measurements, the test provides a single score, the IntelliSep Index (ISI), ranging from 0.1-10.0, stratified into three discrete interpretation bands (Band 2, Band 3) of sepsis likelihood.
6 Intended Use
The Cytovale IntelliSep test is a semi-quantitative test that assesses cellular host response via deformability cytometry of leukocyte biophysical properties and is intended for use in conjunction with clinical assessments and laboratory findings to aid in the early detection of sepsis with organ
5
dysfunction manifesting within the first 3 days after testing. It is indicated for use in adult patients with signs and symptoms of infection who present to the Emergency Department. The test is performed on an EDTA anticoagulated whole blood sample.
The IntelliSep test generates an IntelliSep Index value that falls within one of three discrete interpretation bands based on the probability of sepsis with organ dysfunction manifesting within the first three days after testing. The IntelliSep test represents the probability of the clinical syndrome of sepsis and is intended to be used alongside other clinical information and clinical judgement. It does not identify the causative agent of infection and should not be used as the sole basis to determine the presence of sepsis. The IntelliSep test is intended for in vitro diagnostic use.
7 Indication for Use
See "Intended Use"
8 Overall Comparison Between Subiect Device and Predicate
The indications for use for both the subject and predicate devices are comparable, as they are both intended for use in conjunction with other laboratory findings and clinical assessments to aid in the risk assessment of sepsis in acute patient populations. The indications for use for the subject and predicate devices differ in the type of analytical method used to detect their specific intended assay markers and in the specific subpopulations of acute patients being assessed (e.g., Emergency Dept vs ICU).
Identification and analysis of non-microbial host immune response analytes is the scientific foundation for both the subject and predicate devices. For the predicate device, quantification of procalcitonin is performed to assess the inflammatory response to bacterial infection. The subject device instead quantifies changes in cellular biophysical properties of leukocytes (immune cells) that occur as part of the inflammatory response to infection. While the intended uses of the predicate and subject device are similar, the predicate device measures a released biomarker and the subject device directly evaluates cellular morphology.
Both the predicate and the subject device aid in the identification of sepsis in conjunction with other laboratory findings and clinical assessments. None of the differences constitute a new intended use for the subject device.
| Candidate Device | Predicate Device | |
|---|---|---|
| Item | Cytovale System and IntelliSep test | VIDAS B·R·A·H·M·S PCT |
| (K162827) | ||
| Intended Use / | ||
| Indications for | ||
| Use | The Cytovale IntelliSep test is a semi-quantitative test that assesses cellular host response via deformability cytometry of leukocyte biophysical properties and is intended for use in conjunction with clinical assessments and laboratory findings to aid in the early detection of sepsis with organ dysfunction manifesting within the first 3 days after testing. It is indicated for use in adult patients with signs and symptoms of infection | VIDAS B·R·A·H·M·S PCT is an automated test for use on the instruments of the VIDAS family for the determination of human procalcitonin in human serum or plasma (lithium heparinate) using the ELFA (Enzyme-Linked Fluorescent Assay) technique. |
| Used in conjunction with other laboratory findings and clinical assessments, VIDAS | ||
| Item | Candidate Device | Predicate Device |
| Cytovale System and IntelliSep test | ||
| who present to the Emergency Department. | ||
| The test is performed on an EDTA | ||
| anticoagulated whole blood sample. |
The IntelliSep test generates an IntelliSep
Index value that falls within one of three
discrete interpretation bands based on the
probability of sepsis with organ dysfunction
manifesting within the first three days after
testing. The IntelliSep test represents the
probability of the clinical syndrome of sepsis
and is intended to be used alongside other
clinical information and clinical judgement. It
does not identify the causative agent of
infection and should not be used as the sole
basis to determine the presence of sepsis. The
IntelliSep test is intended for in vitro
diagnostic use. | VIDAS B·R·A·H·M·S PCT
(K162827)
B·R·A·H·M·S PCT is intended for use as
follows:
• to aid in the risk assessment of
critically ill patients on their first day
of ICU admission for progression to
severe sepsis and septic shock, to aid
in assessing the cumulative 28-day
risk of all-cause mortality for patients
diagnosed with severe sepsis or septic
shock in the ICU or when obtained in
the emergency department or other
medical wards prior to ICU
admission, using a change in PCT
level over time,
• to aid in decision making on
antibiotic therapy for patients with
suspected or confirmed lower
respiratory tract infections (LRTI)
defined as community-acquired
pneumonia (CAP), acute bronchitis,
and acute exacerbation of chronic
obstructive pulmonary disease
(AECOPD) – in an inpatient setting
or an emergency department,
• to aid in decision making on
antibiotic discontinuation for patients
with suspected or confirmed sepsis. |
| Site of Use | To be performed by trained laboratory
personnel in a clinical or hospital laboratory
setting | To be performed by a trained operator in a
professional setting, such as a hospital central
laboratory |
| Specimen Type | Human venous whole blood (K2 EDTA) | Human serum, plasma (lithium heparinate) |
| Specimen
Stability | Five (5) hours after draw at ambient
conditions | The sera or plasma separated from the clot can
be stored at 2-8°C in stoppered tubes for up to
48 hours; if longer storage is required, freeze
at -25 ± 6°C. Six-month storage of frozen
samples does not affect the quality of results.
Three freeze/thaw cycles were validated |
| Specimen
Processing | 1. Automated closed system (Sample
Preparation Module) which only operates with
proprietary reagents.
2. The operator transfers the processed sample
into the IntelliSep Cartridge which is inserted
into the Cell Imaging Module for analysis. | Instruments of the VIDAS family: VIDAS,
miniVIDAS or VIDAS 3, using conjugate and
solid phase antibodies and custom reagents |
| Analyte(s) | Leukocyte biophysical properties | Procalcitonin (PCT) |
| Item | Candidate Device | Predicate Device |
| Assay
Principle/Method | Microfluidic deformability cytometry | Quantitative immunofluorescent assay, based
on Sandwich immunoassay principles, which
measures a specific fluorescence signature
(fluorescence (ELFA) of 4-methyl-
umbelliferyl measured at 450 nm) that is
proportional to the antigen (PCT)
concentration. |
| Controls | IntelliSep Quality Control Kit including two
levels of controls derived from stabilized
whole blood:
• Level 1 Control
• Level 2 Control | Two levels of antigen concentration. Each vial
contains lyophilized recombinant PCT in
TRIS NaCl buffer (pH 7.3) and preservatives. |
| Instrument
Platform | Cytovale System | Instruments of the VIDAS family: VIDAS,
miniVIDAS or VIDAS 3 |
| Result Output | The IntelliSep Index (ISI, range 0.1 to 10.0)
that falls within one of three discrete
interpretation bands (Band 1, Band 2, Band 3)
based on likelihood of sepsis within three (3)
days of testing | Calculated estimate of concentration of
circulating PCT, in units of ng/mL |
| Reagent Stability | 1. In original shipping containers unopened at
ambient temperature (15-30°C): up to the
stated expiration date;
2. After opening, onboard at ambient
temperature (15-30°C): 30 days | 1. In original shipping containers unopened at
2-8°C: up to the stated expiration date (12
months);
2. After opening, onboard at 2-8 °C: 29 days |
| Limitations | • Using a different Sample Preparation
Tube than the one provided may lead to
erroneous results.
• Smeared blood on the side of the Sample
Preparation Tube may cause the test to
fail. Remove blood smears from the sides
of the sample preparation tube using the
specified lint-free foam swab. Using a
different swab other than the one required
may lead to no result returned.
• $100 \mu L \pm 5 \mu L$ of specimen volume is
needed for sample preparation. An
erroneous result may occur if the volume
of the sample transferred to the Sample
Preparation Tube is different from the
required volume.
• Use only EDTA anticoagulated whole
blood within 5 hours of collection.
• Predictive values (estimated probabilities
of sepsis) are dependent on prevalence of
disease and likelihood ratios measured for | VIDAS B·R·A·H·M·S PCT (PCT) is not
indicated to be used as a standalone diagnostic
assay and should be used in conjunction with
clinical signs and symptoms of infection and
other diagnostic evidence.
Decisions regarding antibiotic therapy should
NOT be based solely on procalcitonin
concentrations.
PCT results should always be interpreted in
the context of the clinical status of the patient
and other laboratory results. Changes in PCT
levels for the prediction of mortality, and
overall mortality, are strongly dependent on
many factors, including pre-existing patient
risk factors and clinical course.
The need to continue ICU care at Day 4 and
other covariates (e.g., age and SOFA score) |
| | Candidate Device | Predicate Device |
| Item | Cytovale System and IntelliSep test | VIDAS B·R·A·H·M·S PCT
(K162827) |
| | the clinical trial population as reported in
the Clinical Performance Summary. Users
should establish or verify that these
parameter values are appropriate for the
patient population being tested.
The clinical performance has not been
established in the following populations:
Patients below 18 years of age. Patients with a history of a hematologic
malignancy (any leukemia, lymphoma, or
myeloma), myelodysplastic syndrome, or
myeloproliferative disorder Patients who have undergone a
hematopoietic stem cell transplant or any
solid organ transplant Patients receiving a cytotoxic
chemotherapeutic agent in the past 3
months Patients who are residents or patients of a
hospital-based skilled nursing facility Patients who received systemic
corticosteroids were not excluded from
the clinical study. However, the study was
not powered to evaluate the performance
of the ISI specifically in this population
and as such clinical performance has not
been established in this population. Patients with pre-existing end stage renal
disease (ESRD) who undergo
hemodialysis were not excluded from the
clinical study. However, the study was not
powered to evaluate the performance of
the ISI specifically in this population and
as such clinical performance has not been
established in this population. This test was not evaluated for sequential
monitoring of patients, or for use in
patients past the initial ED encounter. The clinical study was not adequately
powered to evaluate differences in
demographics and subpopulations,
therefore results should be interpreted in
conjunction with clinical assessments and
other laboratory findings. | are also significant predictors of 28-day
cumulative mortality risk.
Certain patient characteristics, such as severity
of renal failure or insufficiency, may influence
procalcitonin values and should be considered
as potentially confounding clinical factors
when interpreting PCT values.
Increased PCT levels may be observed in
severe illness such as polytrauma, burns,
major surgery, prolonged or cardiogenic
shock.
PCT levels may not be elevated in patients
infected by certain atypical pathogens, such as
Chlamydophila pneumoniae and Mycoplasma
pneumoniae.
The safety and performance of PCT-guided
therapy for individuals younger than age 17
years, pregnant women, immunocompromised
individuals or those on immunomodulatory
agents, was not formally analyzed in the
supportive clinical trials. |
Information related to this comparison is tabulated in Table 3.
6
7
8
Table 3: Comparison between subject device and predicate device
9
9 Performance Testing
Clinical Performance Summary 9.1
Cytovale conducted a blinded, prospective, observational, multicenter cohort study at five hospitals at four geographically dispersed sites comprised of both academic and community hospital Emergency Departments (EDs) in the United States. The study cohort was representative of the adult population (≥ 18 years of age) typical of those presenting to EDs across the United States with signs or suspicion of infection (defined as meeting two or more Systemic Inflammatory Response Syndrome (SIRS) criteria where one must be aberration of temperature or white blood cell count OR an order placed for cultures of blood, sputum, urine, or sterile body fluids).
599 subjects were enrolled in the study and 572 evaluable subjects were included in the primary analyses. As shown in Table 4, subjects spanned across ranges of age (18 to 103 years of age; 33% of subjects ≥ 65), race (62% white, 30% Black or African American, 2% Asian, and 6% other), ethnicity (6% Hispanic), and sex (44% female). They encompassed those with common comorbidities, including but not limited to diabetes, hypertension, chronic kidney disease, cancer, and obesity. Infection sources affecting or originating from all major organ systems (i.e., respiratory, genitourinary, skin, gastrointestinal, cardiovascular system, central nervous system, and bone) were represented in the study. Additionally, because this study was conducted during the COVID-19 pandemic, 9% of the subjects enrolled in the study were SARS-CoV-2 positive.
The IntelliSep test was performed on an EDTA anticoagulated whole blood sample obtained within 4 hours of the first recorded vital sign (triage). Subsequently, subjects were followed with retrospective chart review for outcome information. Subjects received standard of care and treating physicians were unaware of study enrollment and IntelliSep test results.
| Population Characteristic | | Total | Sepsis Status
(Sepsis-3 Forced) | |
|--------------------------------------|----------------------------------------------|--------------------|------------------------------------|-----------------------|
| | | (N = 572) | Positive
(N = 152) | Negative
(N = 420) |
| | Median (Q1 - Q3) | 56.0 (40.0 - 68.0) | 63.0 (46.0 - 73.0) | 53.00 (37.0 - 66.0) |
| Age | Subjects ≥ 65
N (%) | 187 (32.69%) | 69 (45.39%) | 118 (28.10%) |
| Sex | Female | 250 (43.71%) | 57 (37.50%) | 193 (45.95%) |
| N (%) | Male | 322 (56.29%) | 95 (62.50%) | 227 (54.05%) |
| Ethnicity | Hispanic | 35 (6.12%) | 5 (3.29%) | 30 (7.14%) |
| N (%) | Non-Hispanic | 527 (92.13%) | 145 (95.39%) | 382 (90.95%) |
| | Not Provided | 10 (1.75%) | 2 (1.32%) | 8 (1.90%) |
| | American Indian or
Alaska Native | 8 (1.40%) | 1 (0.66%) | 7 (1.67%) |
| | Asian | 10 (1.75%) | 0 (0.00%) | 10 (2.38%) |
| Race
N (%) | Black or African
American | 172 (30.07%) | 42 (27.63%) | 130 (30.95%) |
| | Native Hawaiian or Other
Pacific Islander | 6 (1.05%) | 2 (1.32%) | 4 (0.95%) |
| | White | 356 (62.24%) | 101 (66.45%) | 255 (60.71%) |
| | Other | 20 (3.50%) | 6 (3.95%) | 14 (3.33%) |
| Source of | Bone / Joint | 19 (6.64%) | 11 (7.24%) | 8 (5.97%) |
| infection in | Cardiovascular System | 20 (6.99%) | 13 (8.55%) | 7 (5.22%) |
| Subjects | Central Nervous System | 13 (4.55%) | 12 (7.89%) | 1 (0.75%) |
| Adjudicated as
Infected, multiple | Gastrointestinal /
Abdominal | 32 (11.19%) | 17 (11.18%) | 15 (11.19%) |
10
| Population Characteristic | | Total
(N = 572) | Sepsis Status
(Sepsis-3 Forced) | |
|-------------------------------------------------------|-----------------------------------------|--------------------|------------------------------------|-----------------------|
| | | | Positive
(N = 152) | Negative
(N = 420) |
| sources included
per subject
(N, % of infected) | Respiratory System | 125 (43.71%) | 81 (53.29%) | 44 (32.84%) |
| | Skin | 57 (19.93%) | 21 (13.82%) | 36 (26.87%) |
| | Urine & Urine System /
Genitourinary | 76 (26.57%) | 49 (32.24%) | 27 (20.15%) |
| | Other or Unknown | 24 (8.39%) | 11 (7.24%) | 13 (9.70%) |
| SARS-CoV-2
Testing
N (%) | Number Tested | 391 (68.36%) | 128 (84.21%) | 263 (62.62%) |
| | Number Positive (of
Tested) | 54 (13.81%) | 37 (28.91%) | 17 (6.46%) |
| | Number Positive (of
Total) | 54 (9.44%) | 37 (24.34%) | 17 (4.05%) |
Table 4: Study population characteristics per sepsis-3 consensus definition in the forced adjudication scheme)
The performance of the IntelliSep test was evaluated by comparison to non-reference retrospective physician adjudication. As detailed below, all subjects were adjudicated by two qualified physicians following the consensus definitions for Sepsis-2 and Sepsis-3. Discordant results were arbitrated through a committee meeting that included a third physician. The adjudication process determined each case to be 'Sepsis' with 'unanimous', 'consensus' or 'forced' determinations for both Sepsis-3 consensus definitions. No cases were excluded due to inability to arbitrate. All study personnel, including study adjudicators. were blinded to the IntelliSep test results.
A multi-tiered adjudication process was utilized to standardize and reduce the inherent subjectivity and variability of using a non-reference comparator. Approximately 30 days after the subject was enrolled, a chart review, using a structured case report form (CRF), was performed. All sites were required to extract the same information to enable adjudication based on the case report form. The information captured included demographics, laboratory results, vital signs, past medical history, hospital encounter information, infectious disease information, medications, and discharge disposition. Additionally, objective evidence of infection (present at the time of ED presentation) and organ dysfunction (manifesting within 3 days following ED presentation) using the Sequential (sepsis-related) Organ Failure Assessment (SOFA) score was captured. Furthermore, a clinical impression was prepared by designated study-trained physicians that were not involved in the subject's care.
Information obtained from the Demographic and Clinical Case Report Forms, Objective Evaluation, and the clinical impression was then compiled into a case report summary (CRS) and sent to two independent adjudicators. If the two adjudicators agreed in their determination, the case was considered 'unanimous' adjudication. If there was disagreement, the CRS was sent to a third adjudicator and a consensus meeting was held. If all could agree, the case fell under 'consensus' or if following discussion consensus could not be reached, a 'forced' (majority two out of three) adjudication determination was reached. The study independent adjudication committee comprised of physicians with board certification in Medical or Surgical Critical Care (CC), Infectious Diseases (ID), Emergency Medicine (EM) or Internal Medicine (IM) or related fields, from different institutions who were not participating as an Investigator in the Study. Individual cases were assigned to the adjudicators by a third-party vendor, without involvement from Cytovale. Adjudicators were blinded to the identity of the Site Investigators and Medical Monitors.
11
The prevalence of sepsis, using the forced Sepsis-3 consensus definition adjudication scheme, was 26.6%. Results across all approaches to analyzing retrospective physician adjudication results were consistent, i.e., a clear relationship was observed between IntelliSep Index (IST) and the increasing likelihood of having or developing sepsis within 3 days across (Figure 2). Irrespective of the comparator scheme chosen, the probability of sepsis in the three ISI IntelliSep test Interpretation Bands was statistically distinct, defined as non-overlapping 80% confidence intervals between the bands (Table 5 through Table 7). It is important to note that the algorithm for calculating the ISI ranges for the interpretation bands were defined based on prior sepsisfocused studies. No information from patients in this study influenced the calculations or interpretation bands of the ISI.
Image /page/11/Figure/3 description: The image contains nine scatter plots arranged in a 3x3 grid, each displaying the "Sepsis Predictive Value" on the y-axis against three "Bands" on the x-axis. The plots are grouped into three rows labeled (A), (B), and (C), representing different Sepsis conditions: "Sepsis-3", "Sepsis-2 (Sepsis)", and "Sepsis-2 (Severe Sepsis)", respectively. Within each row, the plots illustrate different adjudication schemes: "Forced Adjudication Scheme", "Consensus Adjudication Scheme", and "Unanimous Adjudication Scheme". Each data point on the scatter plots represents the sepsis predictive value for a specific band, with error bars indicating the variability or uncertainty associated with each value.
Figure 2: Plots of sepsis predictive value in each band across all approaches to analyzing retrospective physician adjudication results: (A) Sepsis-3 consensus definition, (B) Sepsis 2 consensus definition, (B) Severe Sepsis-2 consensus definition, (C) Severe Sepsis-2 consensus definition, for forced, consensus, and unanimous adjudication schemes.
12
| Sepsis-3 consensus definition, forced adjudication scheme (n=572) | ||||
|---|---|---|---|---|
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | |
| (80% CI) | Sepsis Likelihood | |||
| Ratio | ||||
| Band 1 | 28 | 224 | 11.1% (8.6%, 14.1%) | 0.35 |
| Band 2 | 45 | 115 | 28.1% (23.5%, 33.2%) | 1.08 |
| Band 3 | 79 | 81 | 49.4% (44.0%, 54.7%) | 2.69 |
| Sepsis Prevalence | ||||
| Total | 152 | 420 | 26.6% | NA |
| Sepsis-3 consensus definition, consensus adjudication scheme (n=570) | ||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | |
| (80% CI) | Sepsis Likelihood | |||
| Ratio | ||||
| Band 1 | 28 | 222 | 11.2% (8.7%, 14.2%) | 0.35 |
| Band 2 | 45 | 115 | 28.1% (23.5%, 33.2%) | 1.08 |
| Band 3 | 79 | 81 | 49.4% (44.0%, 54.7%) | 2.68 |
| Sepsis Prevalence | ||||
| Total | 152 | 418 | 26.7% | NA |
| Sepsis-3 consensus definition, unanimous adjudication scheme (n=450) | ||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | |
| (80% CI) | Sepsis Likelihood | |||
| Ratio | ||||
| Band 1 | 20 | 186 | 9.7% (7.1%, 12.9%) | 0.31 |
| Band 2 | 34 | 86 | 28.3% (23.0%, 34.3%) | 1.14 |
| Band 3 | 62 | 62 | 50.0% (43.9%, 56.1%) | 2.88 |
| Sepsis Prevalence | ||||
| Total | 116 | 334 | 25.8% | NA |
Table 5: Distribution of subjects, sepsis prevalence, and sepsis likelihood ratios in the three ISI IntelliSep test Interpretation Bands for Sepsis-3 consensus definition for forced, consensus, and unanimous adjudication schemes.
13
| Sepsis-2 (sepsis) consensus definition, forced adjudication scheme (n=517) | |||||
|---|---|---|---|---|---|
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | ||
| (80% CI) | Sepsis Likelihood | ||||
| Ratio | |||||
| Band 1 | 60 | 154 | 28.0% (24.0%, 32.4%) | 0.38 | |
| Band 2 | 88 | 60 | 59.5% (53.9%, 64.9%) | 1.44 | |
| Band 3 | 113 | 42 | 72.9% (67.8%, 77.6%) | 2.64 | |
| Sepsis Prevalence | |||||
| Total | 261 | 256 | 50.5% | NA | |
| Sepsis-2 (sepsis) consensus definition, consensus adjudication scheme (n=516) | |||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | ||
| (80% CI) | Sepsis Likelihood | ||||
| Ratio | |||||
| Band 1 | 60 | 153 | 28.2% (24.2%, 32.5%) | 0.38 | |
| Band 2 | 88 | 60 | 59.5% (53.9%, 64.9%) | 1.43 | |
| Band 3 | 113 | 42 | 72.9% (67.8%, 77.6%) | 2.63 | |
| Sepsis Prevalence | |||||
| Total | 261 | 255 | 50.6% | NA | |
| Sepsis-2 (sepsis) consensus definition, unanimous adjudication scheme (n=411) | |||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value | ||
| Prevalence (80% CI) | Sepsis Likelihood | ||||
| Ratio | |||||
| Band 1 | 37 | 143 | 20.6% (16.7%, 24.9%) | 0.34 | |
| Band 2 | 58 | 54 | 51.8% (45.3%, 58.2%) | 1.41 | |
| Band 3 | 83 | 36 | 69.8% (63.7%, 75.3%) | 3.02 | |
| Sepsis Prevalence | |||||
| Total | 178 | 233 | 43.3% | NA |
Table 6: Distribution of subjects, sepsis prevalence, and sepsis likelihood ratios in the three ISI IntelliSep test Interpretation Bands for sepsis per Sepsis-2 consensus definition for forced, consensus, and unanimous adjudication schemes.
14
| Sepsis-2 (severe sepsis) consensus definition, forced adjudication scheme (n=517) | ||||
|---|---|---|---|---|
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value (80% CI) | Sepsis Likelihood Ratio |
| Band 1 | 34 | 180 | 15.9% (12.7%, 19.6%) | 0.31 |
| Band 2 | 65 | 83 | 43.9% (38.4%, 49.5%) | 1.28 |
| Band 3 | 97 | 58 | 62.6% (57.2%, 67.7%) | 2.74 |
| Sepsis Prevalence | ||||
| Total | 196 | 321 | 37.9% | NA |
| Sepsis-2 (severe sepsis) consensus definition, consensus adjudication scheme (n=516) | ||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value (80% CI) | Sepsis Likelihood Ratio |
| Band 1 | 34 | 179 | 16.0% (12.8%, 19.7%) | 0.31 |
| Band 2 | 65 | 83 | 43.9% (38.4%, 49.5%) | 1.28 |
| Band 3 | 97 | 58 | 62.6% (57.2%, 67.7%) | 2.73 |
| Sepsis Prevalence | ||||
| Total | 196 | 320 | 38.0% | NA |
| Sepsis-2 (severe sepsis) consensus definition, unanimous adjudication scheme (n=411) | ||||
| IntelliSep Result | Adjudicated + | Adjudicated - | Sepsis Predictive Value (80% CI) | Sepsis Likelihood Ratio |
| Band 1 | 20 | 160 | 11.1% (8.2%, 14.7%) | 0.25 |
| Band 2 | 43 | 69 | 38.4% (32.3%, 44.8%) | 1.23 |
| Band 3 | 75 | 44 | 63.0% (56.8%, 68.9%) | 3.37 |
| Sepsis Prevalence | ||||
| Total | 138 | 273 | 33.6% | NA |
Table 7: Distribution of subjects, sepsis prevalence, and sepsis likelihood ratios in the three ISI Interpreation Bands for severe sepsis per Sepsis-2 consensus definition for forced, consensus, and unanimous adjudication schemes.
The IntelliSep ISI risk stratification score trended upwards with the adjudication determination of sepsis independent of demographic groups (age, sex, race, and ethnicity; Table 8). Additionally, trends were observed between increasing ISI values across the Interpretation bands and hospital care metrics (e.g., hospital admission, ICU admission and transfer, hospital length of stay, and administration of antibiotics; Table 9). It is important to note, that the study was not designed nor powered to evaluate endpoints with regards to severity of illness or hospital care metrics (e.g., mortality, severity of illness scores, hospital admission and length
15
of stay, etc.) and any significant trends or correlations observed between these metrics and the ISI and its Interpretation bands are only observational.
Additionally, subjects who have received systemic corticosteroids and subjects with preexisting end stage renal disease (ESRD) who undergo hemodialysis were not excluded from the clinical study, however, the study was not powered to evaluate the performance of the ISI specifically in these subpopulations.
| Population Characteristic | IntelliSep test Results | |||
|---|---|---|---|---|
| Band 1 | ||||
| (N = 252) | Band 2 | |||
| (N = 160) | Band 3 | |||
| (N = 160) | ||||
| Age | Median (Q1 – Q3) | 54.0 (39.5 - 67.0) | 56.0 (39.0 - 68.0) | 58.0 (41.5 - 71.0) |
| Subjects ≥ 65, N (%) | 77 (30.56%) | 54 (33.75%) | 56 (35.00%) | |
| Sex, N (%) | Female | 106 (42.06%) | 68 (42.50%) | 76 (47.50%) |
| Male | 146 (57.94%) | 92 (57.50%) | 84 (52.50%) | |
| Ethnicity, N (%) | Hispanic | 20 (7.94%) | 8 (5.00%) | 7 (4.38%) |
| Non-Hispanic | 227 (90.08%) | 148 (92.50%) | 152 (95.00%) | |
| Not Provided | 5 (1.98%) | 4 (2.50%) | 1 (0.62%) | |
| Race (%) | American Indian or Alaska Native | 2 (0.79%) | 3 (1.88%) | 3 (1.88%) |
| Asian | 7 (2.78%) | 2 (1.25%) | 1 (0.62%) | |
| Black or African American | 76 (30.16%) | 47 (29.38%) | 49 (30.62%) | |
| Native Hawaiian or Other Pacific Islander | 3 (1.19%) | 0 (0.00%) | 3 (1.88%) | |
| White | 154 (61.11%) | 104 (65.00%) | 98 (61.25%) | |
| Other | 10 (3.97%) | 4 (2.50%) | 6 (3.75%) |
Table 8: Study population demographic characteristics per IntelliSep test interpretation bands.
| Population Characteristic | IntelliSep test Results | ||||
|---|---|---|---|---|---|
| Total | |||||
| (N = 572) | Band 1 | ||||
| (N = 252) | Band 2 | ||||
| (N = 160) | Band 3 | ||||
| (N = 160) | |||||
| All-Cause | 3-day | 3 (0.52%) | 1 (0.40%) | 0 (0.00%) | 2 (1.25%) |
| Cumulative In- | |||||
| Hospital Mortality | |||||
| N (%) | 7-day | 9 (1.57%) | 3 (1.19%) | 1 (0.62%) | 5 (3.12%) |
| 30-day | 24 (4.20%) | 6 (2.38%) | 7 (4.38%) | 11 (6.88%) | |
| Admitted to Hospital, N (%) | 360 (62.94%) | 123 (48.81%) | 107 (66.88%) | 130 (81.25%) | |
| Admitted to ICU, N (%) | 71 (12.41%) | 20 (7.94%) | 23 (14.38%) | 28 (17.50%) | |
| Transferred to ICU within 3 Days, N | |||||
| (%) | 25 (4.37%) | 1 (0.40%) | 15 (9.38%) | 9 (5.62%) | |
| Length of stay | |||||
| Median (Q1-Q3) | Alive at 30 days | 3.0 (0.0 - 7.0) | 2.0 (0.0 - 4.0) | 4.0 (0.0 - 8.0) | 5.0 (3.0 - 9.0) |
| Deceased in- | |||||
| hospital within | |||||
| 30 days | 8.5 (6.5 - 14.5) | 9.0 (5.5 - 12.0) | 9.0 (8.5 - 12.5) | 8.0 (5.0 - 16.5) | |
| ICU Length of | |||||
| stay | |||||
| Median (Q1 - Q3) | Alive at 30 days | 0.0 (0.0 - 0.0) | 0.0 (0.0 - 0.0) | 0.0 (0.0 - 0.0) | 0.0 (0.0 - 0.0) |
| Deceased in- | |||||
| hospital within | |||||
| 30 days | 6.5 (2.0 - 12.5) | 5.5 (0.0 - 11.5) | 8.0 (7.0 - 11.0) | 5.0 (2.0 - 10.0) | |
| Antibiotics | |||||
| Prescribed | Yes | 301 (52.62%) | 99 (39.29%) | 81 (50.62%) | 121 (75.62%) |
| No | 267 (46.68%) | 152 (60.32%) | 77 (48.12%) | 38 (23.75%) | |
| N (%) | Unknown | 4 (0.70%) | 1 (0.40%) | 2 (1.25%) | 1 (0.62%) |
Table 9: Study population severity of illness and hospital course characteristics per IntelliSep test interpretation bands. Note: In the calculation of APACHE II scores, for whom a lab value was not collected per standard of care, the value was considered normal.
16
9.2 Descriptive (Non-Powered) Analyses
In addition to examining study endpoints, descriptive non-powered analyses were performed to explore test performance by demographic subgroups. These non-powered descriptive analyses evaluated the association of IntelliSep Index (expressed in terms of its Interpretation Bands) with the predictive value of sepsis (an adjudicated non-reference method) using the Sepsis-3 consensus standard definition, for demographic subgroups split by age and sex.
The association was examined by the non-overlap of the 80% confidence intervals around point estimates for the probability of sepsis in Band 1 and Band 3 These descriptive analyses were performed using a forced adjudication scheme with evaluable subjects and are shown in Table 10 and Figure 3 (age,