(270 days)
The Edwards Lifesciences Acumen Hypotension Prediction Index feature provides the clinician with physiological insight into a patient's likelihood of future hypotensive events (defined as mean arterial pressure < 65 mmHg for at least one minute in duration) and the associated hemodynamics. The Acumen HPI feature is intended for use in surgical or nonsurgical patients receiving advanced hemodynamic monitoring. The Acumen HPI feature is considered to be additional quantitative information regarding the patient's physiological condition for reference only and no therapeutic decisions should be made based solely on the Hypotension Prediction Index (HPI) parameter.
The Acumen Hypotension Prediction Index feature consists of software running on the Edwards Lifesciences HemoSphere Advanced Monitoring Platform paired with the Acumen IQ extravascular blood pressure transducer (K152980) and a peripheral arterial catheter. The monitoring system includes the Acumen Hypotension Prediction Index (HPI), and graphical user interface features displaying hemodynamic parameters relevant to assessing the root cause of a potential hypotensive event. The Acumen Hypotension Prediction Index is an index related to the likelihood of a patient experiencing hemodynamic instability defined as a hypotensive event* within 15 minutes, where zero (0) indicates low likelihood and one hundred (100) indicates a hypotensive event is occurring. The Acumen Hypotension Prediction Index parameter (HPI), should not be used exclusively to treat patients. A review of the patient's hemodynamics is recommended prior to initiating treatment. * A hypotensive event is defined as mean arterial pressure (MAP) < 65 mmHg for one minute in duration
Here is the extracted information regarding the acceptance criteria and the study that proves the device meets them:
1. A table of acceptance criteria and the reported device performance
| Acceptance Criteria (Primary Effectiveness Endpoint) | Reported Device Performance (HPI Study) |
|---|---|
| Reduce the mean duration of intraoperative hypotension (defined as MAP < 65 mmHg for at least 1 minute) (IOH) by at least 25% in surgical patients that require advanced hemodynamic monitoring, compared with a historic retrospective control group (MPOG). The incidence of IOH in the MPOG group was 88%. An episode of IOH was defined as a mean arterial pressure (MAP) below 65 for three (3) or more consecutive 20-second events. | The HPI Study met its primary effectiveness endpoint. The HPI Pivotal Subjects (full analysis set, n=406) experienced a mean IOH duration of 11.97 ± 13.92 minutes. This represents a reduction of 57.6% compared to the MPOG historical control mean IOH of 28.20 ± 42.60 minutes (p<0.0001). When considering zero episodes of IOH, there was a 65% reduction (p<0.0001). |
| Secondary Effectiveness Endpoint: Determination of total area under the curve (AUC) of the time and MAP for all time periods for which MAP < 65 mmHg in each Subject. This endpoint is correlated with duration, and a descriptive analysis was presented. | AUC results were provided for various subject groups: - All pivotal Subjects (n=457): Mean AUC = 46.38 MinmmHg - All pivotal Subjects with at least one episode (n=328): Mean AUC = 64.63 MinmmHg - All pivotal Subjects with ≥3 hours surgery duration (n=406): Mean AUC = 47.07 MinmmHg - All pivotal Subjects with ≥3 hours surgery duration and at least one IOH episode (n=293): Mean AUC = 65.23 MinmmHg |
| Primary Safety Endpoint: Percentage of serious adverse events (SAEs) to include perioperative events, postoperative complications, and device-related serious adverse events. | - No Subjects had events adjudicated to have any relationship to the Acumen HPI Feature. - No ADEs or SADEs adjudicated as related to the Acumen HPI Feature. - No unanticipated ADEs (0%) related to the HPI Feature. - No deaths occurred that were related/unrelated to the HPI Feature. |
| Secondary Safety Endpoint: Composite measure of complications (Post-operative non-fatal cardiac arrest, In-hospital death, Stroke, Acute Kidney Injury (AKI) within 30 days, Myocardial Injury in non-cardiac surgery (MINS) within 30 days). The study aimed to determine if the guidance provided by the Acumen HPI Feature reduced this composite measure. | In the Completed Cases (CC) population (n=400), the composite event rate was 4.75% (19 events [95% CI: 2.88, 7.32]). Specific events: one non-fatal cardiac arrest (0.25%), 16 AKI (4.00%), 3 MINS (0.75%). No in-hospital deaths or strokes were reported. In the ITT population (n=460), there were 3 (0.66%) MINS and 17 (3.7%) AKI incidents. |
Study Proving Device Meets Acceptance Criteria:
The study proving the device meets the acceptance criteria is titled:
"A Prospective, Single-Arm, Open-Label, Multicenter Study of the Hypotension Prevention and Treatment in Patients Receiving Arterial Pressure Monitoring with Acumen Hypotension Prediction Index Feature (HPI Study)."
2. Sample size used for the test set and the data provenance (e.g. country of origin of the data, retrospective or prospective)
-
Test Set (HPI Study):
- Sample Size: 485 eligible Subjects (460 pivotal with an additional 25 roll-in cases). The Full Analysis Set (FAS) for primary effectiveness included 406 subjects.
- Data Provenance:
- Country of Origin: United States (11 study sites).
- Nature: Prospective, single-arm, unblinded study.
-
Comparison Group (Historical Control):
- Sample Size: 22,109 patients. The population for the primary effectiveness comparison that experienced IOH was 19,445 subjects.
- Data Provenance:
- Country of Origin: United States (from hospitals across the United States).
- Nature: Retrospective historical control group from the Multicenter Perioperative Outcomes Group (MPOG) academic consortium. Dates of data treatment were between January 1, 2017, and December 31, 2017.
3. Number of experts used to establish the ground truth for the test set and the qualifications of those experts (e.g. radiologist with 10 years of experience)
The document does not explicitly state the number of experts or their qualifications for establishing the ground truth related to the MPOG historical control data or the real-time monitoring data from the HPI Study.
However, the "ground truth" for hypotension (MAP < 65 mmHg for at least one minute) is a directly measurable physiological parameter captured by arterial pressure monitoring, which is a standard of care. The definition of IOH (MAP < 65 mmHg for three or more consecutive 20-second events) is based on established clinical understanding and recorded data rather than expert adjudication of an image or subjective finding.
4. Adjudication method (e.g. 2+1, 3+1, none) for the test set
The document does not mention an adjudication method (like 2+1 or 3+1) for establishing the ground truth or evaluating the outcomes in the HPI study. The primary outcome (duration of IOH) and secondary outcomes (AUC, adverse events) were based on directly measured physiological data (MAP) and recorded clinical events, rather than subjective interpretations requiring multiple expert adjudicators. Serious adverse events (SAEs) were "adjudicated," but the specifics of this adjudication process (e.g., number of adjudicators, their roles) are not detailed.
5. If a multi-reader multi-case (MRMC) comparative effectiveness study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
A multi-reader multi-case (MRMC) comparative effectiveness study was not explicitly stated or described as typically understood in the context of image interpretation or diagnostic performance comparison between human readers and AI.
Instead, the study investigated the effectiveness of the Acumen HPI Feature as a decision support tool for clinicians in reducing the duration of IOH. This is a comparative effectiveness study comparing a cohort where clinicians had access to the HPI feature's guidance (HPI Study arm) versus a historical control cohort where clinicians did not have this specific AI-driven predictive guidance (MPOG).
The "effect size" can be considered as the 57.6% reduction in mean IOH duration observed in the HPI arm compared to the MPOG historical control, and a 65% reduction when considering instances with zero IOH episodes. This indicates a significant improvement in patient outcomes (reduced IOH) when clinicians utilize the Acumen HPI Feature for guidance.
6. If a standalone (i.e. algorithm only, without human-in-the-loop performance) was done
The document describes the Acumen HPI Feature as a "decision support tool" providing "physiological insight" and "guidance" for clinicians. The primary effectiveness endpoint specifically evaluates the use of the Acumen HPI Feature to guide intraoperative hemodynamic management. This indicates that the study assessed human-in-the-loop performance, where clinicians were receiving and acting upon the device's output. There is no mention of a standalone algorithm-only performance study.
7. The type of ground truth used (expert consensus, pathology, outcomes data, etc.)
The ground truth used for effectiveness endpoints was physiological measures and clinical outcomes data:
- Intraoperative Hypotension (IOH): Defined as Mean Arterial Pressure (MAP) < 65 mmHg for at least one minute (for the general definition) or for three or more consecutive 20-second events (for the study's specific IOH episode definition), which is directly measurable physiological data from arterial pressure monitoring.
- Area Under the Curve (AUC): Calculated from MAP values below 65 mmHg over time.
- Adverse Events/Complications: Such as cardiac arrest, death, stroke, AKI, and MINS, which are clinical outcomes recorded from patient data.
8. The sample size for the training set
The document does not specify the sample size or details of a training set for the Acumen Hypotension Prediction Index feature algorithm. It mentions that the "Acumen Hypotension Prediction Index (HPI parameter) algorithm as implemented on the HemoSphere Advanced Monitoring Platform (K201446, October 1, 2020) is identical to Acumen Hypotension Prediction Index (HPI parameter) algorithm granted in DEN160044." This suggests the algorithm itself was developed and cleared previously, and the current submission focuses on additional clinical data and labeling modifications.
9. How the ground truth for the training set was established
Since the document does not provide details of a training set for this specific submission, it also does not describe how the ground truth for any training set might have been established. Based on the nature of the device (predicting hypotension), it is highly likely that any prior training would have used large datasets of continuous arterial pressure waveforms and corresponding MAP values as ground truth for hypotensive events, similar to the definition used in the clinical study.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). On the left, there 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, the words "U.S. FOOD & DRUG ADMINISTRATION" are written in blue.
July 30, 2021
Edwards Lifesciences, LLC Lisa Gilman Distinguished Regulatory Affairs Program Manager One Edwards Way Irvine, California 92614
Re: K203224
Trade/Device Name: Acumen™ Hypotension Prediction Index Regulation Number: 21 CFR 870.2210 Regulation Name: Adjunctive predictive cardiovascular indicator Regulatory Class: Class II Product Code: QAQ Dated: October 30, 2020 Received: November 2, 2020
Dear Lisa Gilman:
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 statutes and regulations administered by other Federal agencies. You must comply with all the Act's
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requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801); 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 (OS) 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 mediation-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,
for
Stephen Browning Assistant Director Division of Cardiac Electrophysiology, Diagnostics and Monitoring Devices Office of Cardiovascular Devices Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K203224
Device Name Acumen Hypotension Prediction Index
Indications for Use (Describe)
The Edwards Lifesciences Acumen Hypotension Index feature provides the clinician with physiological insight into a patient's likelihood of future hypotensive events (defined as mean arterial pressure < 65 mmHg for at least one minute in duration) and the associated hemodynamics. The Acumen HPI feature is intended for use in surgical or nonsurgical patients receiving advanced hemodynamic monitoring. The Acumen HPI feature is considered to be additional quantitative information regarding the patient's physiological condition for reference only and no therapeutic decisions should be made based solely on the Hypotension Prediction Index (HPI) parameter.
| 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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SECTION 5 – 510(k) SUMMARY
| Acumen™ Hypotension Prediction Index | |
|---|---|
| Sponsor | Edwards Lifesciences LLCOne Edwards WayIrvine, CA 92614 |
| EstablishmentRegistrationNumber | 2015691 |
| ContactPerson | Lisa GilmanDistinguished Regulatory Affairs Program ManagerOne Edwards WayIrvine, CA 92614Telephone: (949) 250-1478Fax: (949) 809-2996 |
| DatePrepared | June 16, 2021 |
| Trade Name | Acumen™ Hypotension Prediction Index |
| CommonName | Adjunctive Predictive Cardiovascular Indicator |
| ClassificationName | Adjunctive Predictive Cardiovascular Indicator |
| RegulationClass /Product Code | 21 CFR 870.2210/Class II/QAQ |
| PredicateDevice(s) | Acumen Hypotension Prediction Index (HemoSphere Advanced MonitoringPlatform, K201446 (Primary Predicate)Acumen Hypotension Prediction Index, DEN160044 (Reference Predicate) |
| The Acumen Hypotension Prediction Index feature consists of softwarerunning on the Edwards Lifesciences HemoSphere Advanced MonitoringPlatform paired with the Acumen IQ extravascular blood pressure transducer(K152980) and a peripheral arterial catheter. The monitoring system includesthe Acumen Hypotension Prediction Index (HPI), and graphical userinterface features displaying hemodynamic parameters relevant to assessingthe root cause of a potential hypotensive event.* | |
| DeviceDescription | The Acumen Hypotension Prediction Index is an index related to thelikelihood of a patient experiencing hemodynamic instability defined as ahypotensive event* within 15 minutes, where zero (0) indicates lowlikelihood and one hundred (100) indicates a hypotensive event is occurring.The Acumen Hypotension Prediction Index parameter (HPI), should not beused exclusively to treat patients. A review of the patient's hemodynamics isrecommended prior to initiating treatment. |
| * A hypotensive event is defined as mean arterial pressure (MAP) < 65mmHg for one minute in duration | |
| IndicationsforUse/IntendedUse | The Edwards Lifesciences Acumen Hypotension Prediction Index featureprovides the clinician with physiological insight into a patient's likelihood offuture hypotensive events (defined as mean arterial pressure < 65 mmHg forat least one minute in duration) and the associated hemodynamics. The |
| Comparisonto PredicateDevice | The Acumen Hypotension Prediction Index feature as implemented on theHemoSphere Advanced Monitoring Platform (K201446, October 1, 2020) isidentical to itself as there are no changes to the Acumen™ HypotensionPrediction Index feature indications for use, algorithm, nor the hardware andsoftware of the HemoSphere Advanced Monitoring Platform.The Acumen Hypotension Prediction Index (HPI parameter) algorithm asimplemented on the HemoSphere Advanced Monitoring Platform (K201446,October 1, 2020) is identical to Acumen Hypotension Prediction Index (HPIparameter) algorithm granted in DEN160044.ModificationsThe modifications are to the labeling of the HemoSphere AdvancedMonitoring Platform to provide additional data demonstrating theutility of the Acumen™ Hypotension Prediction Index FeatureSoftware in the detection of hemodynamic instability and thetreatment of intraoperative hypotension (IOH) during non-cardiacsurgery. |
| Clinical Performance | |
| A Prospective, Single-Arm, Open-Label, Multicenter Study of theHypotension Prevention and Treatment in Patients Receiving ArterialPressure Monitoring with Acumen Hypotension Prediction Index Feature(HPI Study) was undertaken to further understand the impact that theAcumen Hypotension Prediction Index (HPI) feature may have in thedetection of hemodynamic instability and the treatment of intraoperativehypotension in non-cardiac surgery. The comparison group was aretrospective historical control group with patient-level data from a non-profit academic consortium group, the Multicenter Perioperative OutcomesGroup (MPOG), that collects perioperative data from hospitals across UnitedStates. | |
| PerformanceData | The primary objective of the HPI Study was to determine whether the use ofthe Acumen HPI Feature to guide intraoperative hemodynamic managementin non-cardiac surgery reduces the duration of intraoperative hypotension(defined as MAP < 65 mmHg for at least 1 minute) as compared with ahistoric retrospective control group. The HPI Study was a single-arm,prospective, unblinded study conducted in 485 eligible Subjects (460 pivotalwith an additional 25 roll-in cases) at the same 11 study sites in the UnitedStates that contributed to the historical control group. The HPI arm todetermine if using the Acumen HPI Feature to predict hypotension within 15minutes of an actual event could reduce the mean duration of IOH by at least25%.1 The incidence of IOH in the MPOG group was 88%(n=19,445/22,109) and the dates of treatment were between January 1, 2017and December 31, 2017. The secondary effectiveness endpoint was thedetermination of total area under the curve of the time and MAP for all timeperiods for which MAP < 65 mmHg in each Subject. This endpoint iscorrelated with the duration and a descriptive analysis of this endpoint waspresented with the mean, standard deviation (SD), median, minimum andmaximum. |
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1 Shah NJ, Mentz G, Kheterpal S. The incidence of intraoperative hypotension in moderate to high risk patients undergoing non-cardiac surgery: A retrospective multicenter observational analysis. J Clin Anest. 2020: 66; 109961.
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The primary safety endpoint was the percentage of serious adverse events to include perioperative events, postoperative complications, and device-related serious adverse events. The secondary objective for this study (secondary safety endpoint) was to determine if the guidance provided by the Acumen HPI Feature reduced a composite measure of complications as indicated below:
- Post-operative episodes of non-fatal cardiac arrest;
- In-hospital death; ●
- . Stroke:
- Acute Kidney Injury (AKI) within 30 days of the procedure; ●
- Myocardial Injury in non-cardiac surgery (MINS) within 30 days of . the procedure.
| Description | HPI(Intent-to-Treat) | HPI(Full Analysis Set) | MPOG(Full Analysis Set) | |
|---|---|---|---|---|
| # of patients (N) | 460 | 406* | 22,109 | |
| Gender (%) | Male | 51.7 (n=238) | 52.96 (n=215) | 57.8 (n=12,770) |
| Gender (%) | Female | 48.3 (n=222) | 47.04 (n=191) | 42.2 (n=9330) |
| Age (year) | Mean ± SD | 63.0 ± 13.0 | 62.8 ± 13.0 | 63.3 ± 13.8 |
| Age (year) | Median | 65 (19 - 94) | 65 (19 - 89) | 65 (18 - 90) |
| BMI | Median (25th and 75th percentile) | 28.09 (24.37, 32.81) | 28.09 (24.41, 32.86) | 28.1 (24.2, 32.9) |
| ASA Score (%) | II** | 0.2 (n=1) | 0.25 (n=1) | 0.0 (n=0) |
| ASA Score (%) | III | 91.5 (n=421) | 92.12 (n=374) | 80.83 (n=17,870) |
| ASA Score (%) | IV | 8.0 (n=37) | 7.64 (n=31) | 19.17 (n=4,239) |
| ASA Score (%) | Not specified | 0.2 (n=1) | 0.0 (n=0) | 0.0 (n=0) |
| Surgery duration (minutes) | Mean ± SD | 338.1 ± 145.38(n = 458) | 363.6 ± 134.04 | 355.2 ± 145.8 |
| Surgery duration (minutes) | Median (25th and 75th percentile) | 315.5 (235 - 416)(n = 458) | 336 (262 - 430) | 317 (245, 427) |
Patient Demographics
*The Full Analysis Set (FAS) represent those subjects from the Intent-to-Treat (ITT) population that had a surgery duration of ≥3 hours.
** ASA II subject was identified as a protocol deviation, though not excluded from ITT and FAS populations as this subject met the defined criteria ( surgery > 3 hours and hemodynamic monitoring data). This subject was included in the efficacy and safety analyses, although by inclusion/exclusion criteria should not have been enrolled in the study.
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| Procedure Type (HPI) | |
|---|---|
| Procedure Type | % (n/N) |
| Spine Surgery | 18.5 (85 / 460) |
| Hepatectomy | 13.7 (63 / 460) |
| Whipple | 10.0 (46 / 460) |
| Major, vascular | 8.5 (39 / 460) |
| Other | 8.5 (39 / 460) |
| Nephrectomy | 5.7 (26 / 460) |
| Other Genitourinary Surgery | 5.4 (25 / 460) |
| Cystectomy | 5.0 (23 / 460) |
| Pancreatectomy | 5.0 (23 / 460) |
| Renal Transplant | 4.3 (20 / 460) |
| Head & Neck Surgery | 3.9 (18 / 460) |
| Complex Combined Oncologic Surgery(including 2 or more distinct organs) | 3.0 (14 / 460) |
| Exploratory Laparotomy | 3.0 (14 / 460) |
| Colectomy | 2.8 (13 / 460) |
| Adrenalectomy | 2.6 (12 / 460) |
| Gastrectomy | 2.0 (9 / 460) |
| Other Gastrointestinal Surgery | 2.0 (9 / 460) |
| Hip Revision | 1.7 (8 / 460) |
| Prostatectomy | 1.7 (8 / 460) |
| HIPEC | 1.3 (6 / 460) |
| Hysterectomy with Debulking | 1.3 (6 / 460) |
| Cholecystectomy | 0.9 (4 / 460) |
| Reoperative Orthopedic Surgery | 0.9 (4 / 460) |
| Splenectomy | 0.9 (4 / 460) |
| Bariatric Surgery | 0.4 (2 / 460) |
| Liver Transplant | 0.4 (2 / 460) |
| Sigmoidectomy | 0.4 (2 / 460) |
| Not Specified | 0.2 (1 / 460) |
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Study Results
Effectiveness
The HPI Study was designed to evaluate the ability of the Acumen HPI Feature, as a decision support tool, to reduce the duration of IOH by at least 25% in surgical patients that require advanced hemodynamic monitoring. An episode of intraoperative hypotension (IOH) was defined as a mean arterial pressure (MAP) below 65 for three (3) or more consecutive 20 second events for each subject, across all sites.
The primary effectiveness endpoint is a weighted average of site means and standard deviations combined in the same proportion of subjects that were included in the MPOG cohort. This weighted average and its properly computed standard deviation was compared to the estimates obtained from the subjects of the MPOG cohort.
The HPI Study met its primary effectiveness endpoint. The HPI Pivotal Subjects of the full analysis set experienced a mean IOH duration of 11.97 ± 13.92 minutes compared with the MPOG historical control mean IOH of 28.20 ± 42.60 minutes. The table below demonstrates that this result was a reduction of 57.6% compared to the MPOG historical control (p<0.0001). When considering instances where there were zero episodes of IOH experienced during surgery, there was a 65% reduction of IOH (p<0.0001).
| Statistics | HPI(Subject=406) | MPOG(Subject=22,109) | p value |
|---|---|---|---|
| Sample size (n) | 293 | 19,446 | - |
| Total IOH Minutes | 3,508 | 548,465 | - |
| IOH Mean (mins) | 11.97 | 28.20 | <0.0001* |
| IOH STD | 13.92 | 42.60 | - |
Mean IOH Duration - Primary Effectiveness Endpoint
Note: IOH Estimated with Stand Method; STD Estimated with Pooled Method (Pivotal Subject with IOH Episode in Test Arm). Standard Method - IOH episode is defined with at least three consecutive observations having MAP<65. FAS pivotal Subjects, with at least 3-hour surgery time.
*One-sided unequal variances t-test was used in analysis. Nominal alpha for the test is 0.025.
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The results of the secondary effectiveness endpoint, determination of total area under the curve (AUC) of the time, and MAP for all time periods for which MAP < 65 mmHg in each Subject, are included in the table below.
| Study Category | Subject | AUCMean | AUCSD | AUCMedian | AUCRange | AUCQ3-Q1 |
|---|---|---|---|---|---|---|
| All pivotal Subjects | 457 | 46.38 | 82.75 | 16.67 | 833.00 | 54.00 |
| All pivotal Subjects with atleast one episode | 328 | 64.63 | 91.46 | 32.33 | 832.00 | 68.00 |
| All pivotal Subjects with ≥3hours surgery duration | 406 | 47.07 | 85.30 | 16.83 | 833.00 | 51.00 |
| All pivotal Subjects with ≥ 3hours surgery duration andat least one IOH episode | 293 | 65.23 | 94.36 | 32.00 | 832.00 | 62.67 |
| All pivotal Subjects with <3hours surgery duration | 51 | 40.89 | 58.94 | 12.33 | 291.00 | 71.33 |
| All pivotal Subjects with <3hours surgery duration andat least one IOH episode | 35 | 59.58 | 62.94 | 37.00 | 290.00 | 73.33 |
Intraoperative Hypotension AUC - ITT, Pivotal Subjects (AUC displayed as Min*mmHo)
Note: Standard Method - IOH episode is defined with at least three consecutive observations having MAP<65. ITT pivotal subjects, with valid surgery time.
Safety
The Acumen HPI Feature was shown to be safe when used in surgical patients that require advanced hemodynamic monitoring.
- There were no Subjects with events adjudicated to have any ● relationship to the Acumen HPI Feature.
- There were no ADEs or SADEs adjudicated as related to the Acumen ● HPI Feature.
- There were no unanticipated ADEs (0%) related to the HPI Feature. ●
- There were no deaths that occurred whether related/unrelated to HPI ● Feature.
The secondary safety endpoint was a composite of 30-day post-operative AEs in the completed cases (CC) population. The table below shows the components of the 30-Day post-operative composite endpoint for the Completed Cases (CC) population. The results demonstrate that the composite event rate was 4.75% (composite events =19 [95% CI: 2.88. 7.32], with one subject experiencing more than one of the individual composite elements).
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| Analysis Population (Pivotal Subjects, n=400) | |||||
|---|---|---|---|---|---|
| Analysis Endpoint | AE Event | POD Post-surgery Days | |||
| Events n(%) | 95% CI | Mean | Median | Range | |
| Postoperative Non-FatalCardiac Arrest | 1 (0.25) | 0.01, 1.38 | 2.00 | 2.00 | 2, 2 |
| In-Hospital Death | 0 (0.00) | 0.00, 0.92 | N/A | N/A | N/A |
| Stroke | 0 (0.00) | 0.00, 0.92 | N/A | N/A | N/A |
| Acute Kidney Injury - Overall | 16 (4.00) | 2.30, 6.41 | 5.94 | 1.00 | 0, 27 |
| Acute Kidney Injury - Stage 1 | 11 (2.75) | 1.38, 4.87 | 6.82 | 1.00 | 0, 27 |
| Acute Kidney Injury - Stage 2 | 3 (0.75) | 0.15, 2.18 | 6.33 | 7.00 | 2, 10 |
| Acute Kidney Injury - Stage 3 | 2 (0.50) | 0.06, 1.79 | 0.50 | 0.50 | 0, 1 |
| Myocardial Injury (MINS) | 3 (0.75) | 0.15, 2.18 | 1.67 | 1.00 | 0, 4 |
HPI Study - 30 Days Post-Operative Composite Endpoint Components -CC Analy
CC=Complete (Evaluable) Group, CI=confidence interval, Post-surgery Days (POD)=AESTDT-SGDT
Analysis of in the intent-to-treat population (n=460) vielded 3 (.066%) instances of myocardial injury (MINS) and 17 (3.7%) incidents of acute kidnev injurv (AKI).
Study Summary
These results demonstrate a reduction in mean IOH, that was consistent across most sites; most sites had a > 25% reduction in its mean duration of IOH, with all sites but one exceeding 35%; ranging from a23% to 72% mean IOH reduction. The findings of the study showed a reduction of the duration of IOH to 11.97 mins (SD 13.92), representing a 57.6% reduction (p<0.0001). This reduction is clinically relevant, as IOH lasting at least 1minute has been associated with perioperative complications and morbidity such as AKI, MINS and stroke1.
The results demonstrate that Acumen HPI Feature was shown to be safe when used in surgical patients that require advanced hemodynamic monitoring, with no device-related adverse events. Additionally, the composite event rate 4.75% (composite events =19 [95% CI: 2.88, 7.32] is low when considering that the subjects were ASA Physical Status 3 and 4 undergoing non-cardiac surgery.
Conclusion
The results of this study provide valid scientific evidence that the Acumen HPI feature is safe and provided a clinically significant reduction in mean IOH. Acumen HPI is effective in detecting hemodynamic instability and reducing the amount ofintraoperative hypotension when used in surgical patients who require intraoperative hemodynamic monitoring during noncardiac surgery.
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| Conclusion | Acumen Hypotension Prediction Index Feature as implemented on theHemoSphere Advanced Monitoring Platform (K201446, October 1, 2020) isequivalent to itself as there are no changes to the Acumen HypotensionPrediction Index feature indications for use, algorithm, nor the hardware andsoftware of the HemoSphere Advanced Monitoring Platform. Additionally,the Acumen Hypotension Prediction Index (HPI parameter) algorithm asimplemented on the HemoSphere Advanced Monitoring Platform (K201446,October 1, 2020) is identical to Acumen Hypotension Prediction Index (HPIparameter) algorithm (DEN160044, March 16, 2020).The clinical performance data further demonstrate the utility of the AcumenHypotension Prediction Index Feature Software in the detection ofhemodynamic instability and in the treatment of intraoperative hypotension(IOH) during non-cardiac surgery.The Acumen Hypotension Prediction Index is substantially equivalent to theAcumen Hypotension Prediction Index (HemoSphere Advanced MonitoringPlatform), K201446. |
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§ 870.2210 Adjunctive predictive cardiovascular indicator.
(a)
Identification. The adjunctive predictive cardiovascular indicator is a prescription device that uses software algorithms to analyze cardiovascular vital signs and predict future cardiovascular status or events. This device is intended for adjunctive use with other physical vital sign parameters and patient information and is not intended to independently direct therapy.(b)
Classification. Class II (special controls). The special controls for this device are:(1) A software description and the results of verification and validation testing based on a comprehensive hazard analysis and risk assessment must be provided, including:
(i) A full characterization of the software technical parameters, including algorithms;
(ii) A description of the expected impact of all applicable sensor acquisition hardware characteristics and associated hardware specifications;
(iii) A description of sensor data quality control measures;
(iv) A description of all mitigations for user error or failure of any subsystem components (including signal detection, signal analysis, data display, and storage) on output accuracy;
(v) A description of the expected time to patient status or clinical event for all expected outputs, accounting for differences in patient condition and environment; and
(vi) The sensitivity, specificity, positive predictive value, and negative predictive value in both percentage and number form.
(2) A scientific justification for the validity of the predictive cardiovascular indicator algorithm(s) must be provided. This justification must include verification of the algorithm calculations and validation using an independent data set.
(3) A human factors and usability engineering assessment must be provided that evaluates the risk of misinterpretation of device output.
(4) A clinical data assessment must be provided. This assessment must fulfill the following:
(i) The assessment must include a summary of the clinical data used, including source, patient demographics, and any techniques used for annotating and separating the data.
(ii) The clinical data must be representative of the intended use population for the device. Any selection criteria or sample limitations must be fully described and justified.
(iii) The assessment must demonstrate output consistency using the expected range of data sources and data quality encountered in the intended use population and environment.
(iv) The assessment must evaluate how the device output correlates with the predicted event or status.
(5) Labeling must include:
(i) A description of what the device measures and outputs to the user;
(ii) Warnings identifying sensor acquisition factors that may impact measurement results;
(iii) Guidance for interpretation of the measurements, including a statement that the output is adjunctive to other physical vital sign parameters and patient information;
(iv) A specific time or a range of times before the predicted patient status or clinical event occurs, accounting for differences in patient condition and environment;
(v) Key assumptions made during calculation of the output;
(vi) The type(s) of sensor data used, including specification of compatible sensors for data acquisition;
(vii) The expected performance of the device for all intended use populations and environments; and
(viii) Relevant characteristics of the patients studied in the clinical validation (including age, gender, race or ethnicity, and patient condition) and a summary of validation results.