IntelliSep test

{0}------------------------------------------------ Image /page/0/Picture/0 description: The image shows the logo of the U.S. Food and Drug Administration (FDA). On the left is the Department of Health & Human Services logo. To the right of that is the FDA logo, which is a blue square with the letters "FDA" in white. To the right of the blue square is the text "U.S. FOOD & DRUG ADMINISTRATION" in blue. # 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) # CONTINUE ON A SEPARATE PAGE IF NEEDED. This section applies only to requirements of the Paperwork Reduction Act of 1995. # *DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.* The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to: > Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff@fda.hhs.gov "An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number." {3}------------------------------------------------ | 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)<br>Number | Date of<br>Clearance | Classification | Regulation | Classification<br>Product Code | |--------------------------------|------------------|----------------------|--------------------------------|------------|--------------------------------| | VIDAS B·R·A·H·M·S<br>PCT (PCT) | K162827 | February 23, 2017 | Class II<br>(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:<br>(Required and supplied)<br>• Sample Preparation Module (SPM)<br>• Cell Imaging Module (CIM)<br>• Imaging Analysis Module (IAM) | A closed system benchtop analyzer as shown in Figure 1. It<br>is comprised of three modules: Sample Preparation Module,<br>Cell Imaging Module and Imaging Analysis Module. | | Barcode scanner<br>(Optional and supplied) | Scanner used to automatically enter sample and material<br>identifiers. | | Printer<br>(Optional and supplied) | Printer used to print a hard copy of results. | | Sample Preparation Tube<br>(Required and supplied) | A single-use, commercial off-the-shelf test tube used for<br>sample preparation. | | IntelliSep Cartridge<br>(Required and supplied) | Closed system test cartridge which presents the sample for<br>testing in the Cell Imaging Module. | | Cytovale Reagent Kit<br>(Required and supplied) | Nonbiological salt solutions (Reagent A Lysis and Reagent<br>B Quench), for use with the Sample Preparation Module to<br>lyse red blood cells and quench the lysis reaction. | | Cytovale Diluent and Cleanse Reagents<br>(Required and supplied) | The Diluent solution is used in the Sample Preparation<br>Module to suspend white blood cells for analysis. The<br>Cleanse is a rinsing solution for the SPM. | | IntelliSep Quality Control Kit<br>(Quality controls are required but not<br>supplied) | A two-level Quality Control set, derived from stabilized<br>whole blood.<br>Note: Per 42 CFR 493.1256, quality controls are required for the<br>IntelliSep test; however, at their discretion, laboratory directors<br>may develop their own quality control materials or order the<br>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<br>(K162827) | | Intended Use /<br>Indications for<br>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.<br>Used in conjunction with other laboratory findings and clinical assessments, VIDAS | | Item | Candidate Device | Predicate Device | | | Cytovale System and IntelliSep test<br>who present to the Emergency Department.<br>The test is performed on an EDTA<br>anticoagulated whole blood sample.<br><br>The IntelliSep test generates an IntelliSep<br>Index value that falls within one of three<br>discrete interpretation bands based on the<br>probability of sepsis with organ dysfunction<br>manifesting within the first three days after<br>testing. The IntelliSep test represents the<br>probability of the clinical syndrome of sepsis<br>and is intended to be used alongside other<br>clinical information and clinical judgement. It<br>does not identify the causative agent of<br>infection and should not be used as the sole<br>basis to determine the presence of sepsis. The<br>IntelliSep test is intended for in vitro<br>diagnostic use. | VIDAS B·R·A·H·M·S PCT<br>(K162827)<br><br>B·R·A·H·M·S PCT is intended for use as<br>follows:<br>• to aid in the risk assessment of<br>critically ill patients on their first day<br>of ICU admission for progression to<br>severe sepsis and septic shock, to aid<br>in assessing the cumulative 28-day<br>risk of all-cause mortality for patients<br>diagnosed with severe sepsis or septic<br>shock in the ICU or when obtained in<br>the emergency department or other<br>medical wards prior to ICU<br>admission, using a change in PCT<br>level over time,<br>• to aid in decision making on<br>antibiotic therapy for patients with<br>suspected or confirmed lower<br>respiratory tract infections (LRTI)<br>defined as community-acquired<br>pneumonia (CAP), acute bronchitis,<br>and acute exacerbation of chronic<br>obstructive pulmonary disease<br>(AECOPD) – in an inpatient setting<br>or an emergency department,<br>• to aid in decision making on<br>antibiotic discontinuation for patients<br>with suspected or confirmed sepsis. | | Site of Use | To be performed by trained laboratory<br>personnel in a clinical or hospital laboratory<br>setting | To be performed by a trained operator in a<br>professional setting, such as a hospital central<br>laboratory | | Specimen Type | Human venous whole blood (K2 EDTA) | Human serum, plasma (lithium heparinate) | | Specimen<br>Stability | Five (5) hours after draw at ambient<br>conditions | The sera or plasma separated from the clot can<br>be stored at 2-8°C in stoppered tubes for up to<br>48 hours; if longer storage is required, freeze<br>at -25 ± 6°C. Six-month storage of frozen<br>samples does not affect the quality of results.<br>Three freeze/thaw cycles were validated | | Specimen<br>Processing | 1. Automated closed system (Sample<br>Preparation Module) which only operates with<br>proprietary reagents.<br>2. The operator transfers the processed sample<br>into the IntelliSep Cartridge which is inserted<br>into the Cell Imaging Module for analysis. | Instruments of the VIDAS family: VIDAS,<br>miniVIDAS or VIDAS 3, using conjugate and<br>solid phase antibodies and custom reagents | | Analyte(s) | Leukocyte biophysical properties | Procalcitonin (PCT) | | Item | Candidate Device | Predicate Device | | Assay<br>Principle/Method | Microfluidic deformability cytometry | Quantitative immunofluorescent assay, based<br>on Sandwich immunoassay principles, which<br>measures a specific fluorescence signature<br>(fluorescence (ELFA) of 4-methyl-<br>umbelliferyl measured at 450 nm) that is<br>proportional to the antigen (PCT)<br>concentration. | | Controls | IntelliSep Quality Control Kit including two<br>levels of controls derived from stabilized<br>whole blood:<br>• Level 1 Control<br>• Level 2 Control | Two levels of antigen concentration. Each vial<br>contains lyophilized recombinant PCT in<br>TRIS NaCl buffer (pH 7.3) and preservatives. | | Instrument<br>Platform | Cytovale System | Instruments of the VIDAS family: VIDAS,<br>miniVIDAS or VIDAS 3 | | Result Output | The IntelliSep Index (ISI, range 0.1 to 10.0)<br>that falls within one of three discrete<br>interpretation bands (Band 1, Band 2, Band 3)<br>based on likelihood of sepsis within three (3)<br>days of testing | Calculated estimate of concentration of<br>circulating PCT, in units of ng/mL | | Reagent Stability | 1. In original shipping containers unopened at<br>ambient temperature (15-30°C): up to the<br>stated expiration date;<br>2. After opening, onboard at ambient<br>temperature (15-30°C): 30 days | 1. In original shipping containers unopened at<br>2-8°C: up to the stated expiration date (12<br>months);<br>2. After opening, onboard at 2-8 °C: 29 days | | Limitations | • Using a different Sample Preparation<br>Tube than the one provided may lead to<br>erroneous results.<br>• Smeared blood on the side of the Sample<br>Preparation Tube may cause the test to<br>fail. Remove blood smears from the sides<br>of the sample preparation tube using the<br>specified lint-free foam swab. Using a<br>different swab other than the one required<br>may lead to no result returned.<br>• $100 \mu L \pm 5 \mu L$ of specimen volume is<br>needed for sample preparation. An<br>erroneous result may occur if the volume<br>of the sample transferred to the Sample<br>Preparation Tube is different from the<br>required volume.<br>• Use only EDTA anticoagulated whole<br>blood within 5 hours of collection.<br>• Predictive values (estimated probabilities<br>of sepsis) are dependent on prevalence of<br>disease and likelihood ratios measured for | VIDAS B·R·A·H·M·S PCT (PCT) is not<br>indicated to be used as a standalone diagnostic<br>assay and should be used in conjunction with<br>clinical signs and symptoms of infection and<br>other diagnostic evidence.<br>Decisions regarding antibiotic therapy should<br>NOT be based solely on procalcitonin<br>concentrations.<br>PCT results should always be interpreted in<br>the context of the clinical status of the patient<br>and other laboratory results. Changes in PCT<br>levels for the prediction of mortality, and<br>overall mortality, are strongly dependent on<br>many factors, including pre-existing patient<br>risk factors and clinical course.<br>The need to continue ICU care at Day 4 and<br>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<br>(K162827) | | | the clinical trial population as reported in<br>the Clinical Performance Summary. Users<br>should establish or verify that these<br>parameter values are appropriate for the<br>patient population being tested.<br><br>The clinical performance has not been<br>established in the following populations:<br>Patients below 18 years of age. Patients with a history of a hematologic<br>malignancy (any leukemia, lymphoma, or<br>myeloma), myelodysplastic syndrome, or<br>myeloproliferative disorder Patients who have undergone a<br>hematopoietic stem cell transplant or any<br>solid organ transplant Patients receiving a cytotoxic<br>chemotherapeutic agent in the past 3<br>months Patients who are residents or patients of a<br>hospital-based skilled nursing facility Patients who received systemic<br>corticosteroids were not excluded from<br>the clinical study. However, the study was<br>not powered to evaluate the performance<br>of the ISI specifically in this population<br>and as such clinical performance has not<br>been established in this population. Patients with pre-existing end stage renal<br>disease (ESRD) who undergo<br>hemodialysis were not excluded from the<br>clinical study. However, the study was not<br>powered to evaluate the performance of<br>the ISI specifically in this population and<br>as such clinical performance has not been<br>established in this population. This test was not evaluated for sequential<br>monitoring of patients, or for use in<br>patients past the initial ED encounter. The clinical study was not adequately<br>powered to evaluate differences in<br>demographics and subpopulations,<br>therefore results should be interpreted in<br>conjunction with clinical assessments and<br>other laboratory findings. | are also significant predictors of 28-day<br>cumulative mortality risk.<br><br>Certain patient characteristics, such as severity<br>of renal failure or insufficiency, may influence<br>procalcitonin values and should be considered<br>as potentially confounding clinical factors<br>when interpreting PCT values.<br><br>Increased PCT levels may be observed in<br>severe illness such as polytrauma, burns,<br>major surgery, prolonged or cardiogenic<br>shock.<br><br>PCT levels may not be elevated in patients<br>infected by certain atypical pathogens, such as<br>Chlamydophila pneumoniae and Mycoplasma<br>pneumoniae.<br><br>The safety and performance of PCT-guided<br>therapy for individuals younger than age 17<br>years, pregnant women, immunocompromised<br>individuals or those on immunomodulatory<br>agents, was not formally analyzed in the<br>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 comorbidi…