Heart Failure NYHA Class IIALLEVIATE-HFNCT04452149

Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure

A study testing Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download, Medication intervention and Not Randomized to Device or Medication Intervention in people with Heart Failure NYHA Class II and Heart Failure NYHA Class III, run by Medtronic Cardiac Rhythm and Heart Failure at 53 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure NYHA Class II, Heart Failure NYHA Class III
What is being tested?: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download, Medication intervention and Not Randomized to Device or Medication Intervention
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 826 participants
Where: 53 sitesUnited States
Study dates: 3 Sep 2020to 2 Jun 2025
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient has NYHA Class II or III heart failure per most recent assessment, irrespective of left ventricular ejection fraction (LVEF)
Patient has documented recent history of symptomatic heart failure, defined as meeting any one of the following three criteria: 1. Hospital admission with primary diagnosis of HF within the last 12 months, OR 2. Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration within the last 6 months, OR 3. Patient had the following BNP/NT-proBNP within the last 3 months: If LVEF ≥ 50%, then BNP> 150 pg/ml or NT-proBNP > 450 pg/ml OR If LVEF is <50%, then BNP> 300 pg/ml or NT-proBNP > 900 pg/ml
Patient is willing and able to comply with the protocol, including LINQ ICM insertion, CareLink transmissions (including adequate connectivity), study visits and remote care directions.
Patient is 18 years of age or older.
Patient has a life expectancy of 12 months or more.

Who cannot join

Patient is currently implanted with a cardiovascular implantable electronic device (CIED) (e.g. ICM, pacemaker, ICD, CRT-D or CRT-P device) or hemodynamic monitor.
Patient is receiving temporary or permanent mechanical circulatory support.
Patient had MI or PCI/CABG within past 90 days.
Patient has had a heart transplant, or is currently on heart transplant list.
Patient has severe valve stenosis on echocardiogram.
Patient has primary pulmonary hypertension (pre-capillary, WHO group 1,3,4,5).

Show all 19Show fewer

Patient is on chronic intravenous inotropic drug therapy (e.g. dobutamine, milrinone).
Patient has severe renal impairment (eGFR <30 mL/min).
Patient has systolic blood pressure of < 90 mmHg at the time of enrollment.
Patient is on chronic renal dialysis.
Patient is unable to undergo one round of PRN medication intervention (i.e. 4 days of increased diuretics dose).
Patient has liver disease, defined as AST/ALT >5x normal, or bilirubin >2x normal.
Patient has serum albumin < 3 g/dL.
Patient has hypertrophic obstructive cardiomyopathy, constrictive pericarditis or amyloidosis.
Patient has complex adult congenital heart disease.
Patient has active cancer involving chemotherapy and/or radiation therapy.
Patient weighs more than 500 pounds.
Patient is pregnant or breastfeeding (all females of child-bearing potential must have a negative pregnancy test within 1 week of enrollment).
Patient is enrolled in another interventional study.

Trial locations and contacts

53 sites in 1 country.

City, postcode or hospital

53 sites in 1 country

United States53 sites

New Mexico Heart Institute PA
Albuquerque, New Mexico, 87102
FWD Clinical Research LLC
Boca Raton, Florida, 33486
Bay Area Cardiology Associates PA
Brandon, Florida, 33511
Medical University of South Carolina
Charleston, South Carolina, 29425
Charleston Area Medical Center (CAMC) Memorial Hospital
Charleston, West Virginia, 25304
The Lindner Research Center
Cincinnati, Ohio, 45219
Prisma Health Midlands
Columbia, South Carolina, 29203
Mount Carmel East
Columbus, Ohio, 43213
OhioHealth Research and Innovation Institute (OHRI)
Columbus, Ohio, 43214
Doylestown Health Cardiology a division of Doylestown Health Physicians
Doylestown, Pennsylvania, 18901
Saint Elizabeth Healthcare
Edgewood, Kentucky, 41017
NorthShore University Health System
Evanston, Illinois, 60201
Parkview Health
Fort Wayne, Indiana, 46845
Medical City Fort Worth
Fort Worth, Texas, 76104
Florida Heart Center
Ft. Pierce, Florida, 34950
The Stern Cardiovascular Foundation
Germantown, Tennessee, 38138
Cone Health
Greensboro, North Carolina, 27401
Ascension Medical Group - Saint Vincent
Indianapolis, Indiana, 46260
University of Mississippi Medical Center
Jackson, Mississippi, 39216
Baptist Health
Jacksonville, Florida, 32207
First Coast Cardiovascular Institute PA
Jacksonville, Florida, 32256
Arrhythmia Research Group
Jonesboro, Arkansas, 72410
University of Kansas Medical Center
Kansas City, Kansas, 66160
Citrus Cardiology Consultants PA
Leesburg, Florida, 34748
South Denver Cardiology Associates
Littleton, Colorado, 80120
Baptist Healthcare System
Louisville, Kentucky, 40207
Norton Healthcare
Louisville, Kentucky, 40217
University of Tennessee Methodist Physicians
Memphis, Tennessee, 38104
Cardiovascular Associates of Mesa
Mesa, Arizona, 85282
Saint Joseph Heritage Healthcare
Mission Viejo, California, 92691
West Virginia University
Morgantown, West Virginia, 26506
Columbia University Irving Medical Center/NYPH
New York, New York, 10032
Sentara Norfolk General Hospital
Norfolk, Virginia, 23507
CHI Health Creighton University Medical Center - Bergan Mercy
Omaha, Nebraska, 68124
Cardiology Associates Medical Group
Oxnard, California, 93030
Baptist Hospital
Pensacola, Florida, 32501
Cardiology Consultants of Philadelphia
Philadelphia, Pennsylvania, 19107
Hudson Valley Heart Center
Poughkeepsie, New York, 12601
North Memorial Health Heart & Vascular Center
Robbinsdale, Minnesota, 55422
Saint Francis Hospital
Roslyn, New York, 11576
Memorial Health University Medical Center
Savannah, Georgia, 31404
Swedish Medical Center Cherry Hill
Seattle, Washington, 98122
Northside Hospital
St. Petersburg, Florida, 33709
Saint Joseph's Medical Center
Stockton, California, 95204
Stony Brook University Hospital
Stony Brook, New York, 11794
Saint Joseph Medical Center (Tacoma WA)
Tacoma, Washington, 98405
Tallahassee Research Institute
Tallahassee, Florida, 32308
Cardiology Associates of North Mississippi
Tupelo, Mississippi, 38801
Tyler Cardiovascular Consultants
Tyler, Texas, 75701
Carle Foundation Hospital
Urbana, Illinois, 61801
Lourdes Cardiology Services
Voorhees Township, New Jersey, 08043
Iowa Heart Center
West Des Moines, Iowa, 50266
Novant Health New Hanover Regional Medical Center
Wilmington, North Carolina, 28401

Other trials in United States

About this study

The ALLEVIATE-HF study is a prospective, randomized, controlled, blinded, multi-site, interventional, investigational device exemption (IDE) pivotal study. The purpose of the study is to demonstrate the safety and efficacy of a patient management pathway that utilizes an integrated device diagnostic-based risk stratification algorithm to guide patient care in subjects with NYHA class II and III heart failure, and to demonstrate the safety of the Reveal LINQ™ system and procedure in the study population.

Read the detailed description

The study will utilize the market released Reveal LINQ™ Insertable Cardiac Monitor with an investigational ALLEVIATE-HF RAMware download. The study will enroll up to 900 subjects at up to 75 sites in the US. Subjects will be followed until the last enrolled subject is followed for 7 months or until the end of the study, whichever occurs first, or until time of study exit or death as applicable, but no longer than 36 months.

Conditions: Heart Failure NYHA Class II, Heart Failure NYHA Class III
Being tested: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download, Medication intervention, Not Randomized to Device or Medication Intervention
Keywords: Heart Failure, Insertable Cardiac Monitor
Medical subject headings: Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware downloadDevice
Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.
Medication interventionOther
Risk status guided medication intervention.
Not Randomized to Device or Medication InterventionOther
No intervention was assigned due to not being randomized under the final version of the investigational plan

Study groups in NCT04452149
Study group	Role	What they receive
Observation Arm	Placebo comparator	Subjects will receive a Reveal LINQ™ Insertable Cardiac Monitor with an investigational ALLEVIATE-HF RAMware download, and will be managed per standard of care for heart failure management without visibility to the heart failure sensor data. Subjects will transition to the intervention arm after 13 months. Receives: Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download
Intervention Arm	Experimental	Subjects will receive a Reveal LINQ™ Insertable Cardiac Monitor with an investigational ALLEVIATE-HF RAMware download, and will be managed using an integrated device diagnostic-based risk stratification algorithm combined with a clinical medication plan. Receives: Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download; Other: Medication intervention
Additional Participants Included Only in Safety Set	Other	Participants who were only randomized to an earlier version of the Clinical Investigational Plan and were only analyzed for the secondary safety outcome. The randomization under the previous version was not pertinent to the primary or secondary outcomes, and thus are combined into one group for the main analysis. Receives: Other: Not Randomized to Device or Medication Intervention
Participants Not Included in Study Analyses	Other	Patients who were, with one exception, exited prior to randomization. The exception was a patient who was ineligible for the study analyses due to being enrolled under the previous version of the investigational plan with a pre-existing LINQ device, and thus ineligible for the Analysis Set or the Safety Set. Receives: Other: Not Randomized to Device or Medication Intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

Safety of Patient Management Pathway - Proportion of PRN Medication Interventions With Associated PRN Medication Intervention Related Serious Adverse Events (SAEs)
The proportion of PRN medication interventions with one or more associated medication intervention related serious SAEs as adjudicated by the independent Clinical Events Committee will be evaluated. The objective is met when the point estimate for the event rate is less than or equal to 0.05 (5%).
Measured: From 6 weeks after installation of RAMware through the duration of follow-up for Intervention arm subjects, and from the conclusion of the 13-month randomized period through the duration of follow-up for Observation arm subjects, up to 3 years.
Efficacy of Patient Management Pathway - Hierarchical Composite of Cardiovascular Death, Heart Failure (HF) Events, Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) and Change in Six-minute Walk Test Distance
The win ratio for the hierarchical composite endpoint, defined as Intervention arm wins divided by Observation arm wins, will be evaluated using the Finkelstein-Schoenfeld test. Analysis will include subjects with at least one "high" HF risk status during the analysis period (i.e. between 42 and 395 days post-randomization, to exclude the 6-weeks after the installation of RAMware and include data occurring prior to the 13-month timepoint). HF event, as adjudicated by the independent Clinical Events Committee, is defined as an event requiring invasive HF therapy (e.g. IV or subcutaneous diuretics/vasodilators/inotropes) or ultrafiltration, and includes events with or without hospitalization. The Clinical Composite Score is used as KCCQ measure. The primary efficacy objective is met when the win ratio is significantly larger than 1.0, with a p-value below 0.05.
Measured: From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Secondary outcomes (2)

Safety of Reveal LINQ™ System and Procedure - Percentage of Subjects With Freedom From Experiencing System or Procedure Related Serious Adverse Events
Freedom from Reveal LINQ™ system and procedure related serious adverse events (SAEs) as adjudicated by the independent Clinical Events Committee will be evaluated. The objective is met when freedom from system and procedure related SAEs at 6 months is greater than or equal to 95%.
Measured: From time of Reveal LINQ™ device insertion attempt to 6 months post insertion attempt.
Efficacy of Patient Management Pathway - Hierarchical Composite of Cardiovascular Death, HF Events, Change in KCCQ, Change in Six-minute Walk Test Distance, and Change in Device-measured Activity and Night Heart Rate
The win ratio for the hierarchical composite endpoint, defined as Intervention arm wins divided by Observation arm wins, will be evaluated using the Finkelstein-Schoenfeld test. Analysis will include subjects with at least one "high" HF risk status during the analysis period (i.e. between 42 and 395 days post-randomization, to exclude the 6-weeks after the installation of RAMware and include data occurring prior to the 13-month timepoint). HF event, as adjudicated by the independent Clinical Events Committee, is defined as an event requiring invasive HF therapy (e.g. IV or subcutaneous diuretics/vasodilators/inotropes) or ultrafiltration, and includes events with or without hospitalization. The Clinical Composite Score is used as KCCQ measure. The secondary efficacy objective is met when the win ratio is significantly larger than 1.0, with a p-value below 0.05.
Measured: From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

3 Sep 20202 Jun 2025

First posted30 Jun 2020
Study start3 Sep 2020
Primary completion2 Jun 2025
Study completion2 Jun 2025

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (4)Papers the sponsor has linked to this study.
Other trials for Heart Failure NYHA Class IIStudies of the same condition, open and under way.
More trials run by Medtronic Cardiac Rhythm and Heart FailureThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Following Reveal LINQ™ device insertion, subjects will be randomly allocated in a blinded fashion in a 1:1 ratio to either the observation arm or the intervention arm. Subjects in the observation arm will start with an observational period of 13 months and then transition to the intervention arm for the remainder of their participation in the study.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 826 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04452149
Sponsor's protocol ID: ALLEVIATE-HF
Acronym: ALLEVIATE-HF
Status last verified: Jan 2026
First submitted: 24 Jun 2020
Last updated: 26 Aug 2026
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No

Publications

Butler J, Kahwash R, Khan MS, Zhang D, Dukes JW, Reddy M, Basuray A, Gharib E, Gerritse B, Laechelt A, Wehking J, Sarkar S, Van Dorn B, Patel N, Laager V, Zile MR; ALLEVIATE-HF Investigators. Risk-Based Nurse-Managed Personalized Heart Failure Interventions: The ALLEVIATE-HF Trial. J Am Coll Cardiol. 2026 Jun 30;87(25):3592-3607. doi: 10.1016/j.jacc.2026.03.075. Epub 2026 May 27.
PubMed 42201288
Kahwash R, Butler J, Khan MS, Zhang D, Dukes J, Reddy M, Kaplan RM, Amin A, Kanwar R, Sarkar S, Laager V, Wehking J, Van Dorn B, Gerritse B, Patel N, Laechelt A, Zile MR; ALLEVIATE-HF Investigators. Arrhythmia Burden and Clinical Responses Under Continuous Monitoring in Heart Failure: Observations From the ALLEVIATE-HF Trial. J Am Coll Cardiol. 2026 Jun 30;87(25):3611-3628. doi: 10.1016/j.jacc.2026.03.174. Epub 2026 May 27.
PubMed 42201276
Kahwash R, Zile MR, Chalasani P, Bertolet B, Gravelin L, Khan MS, Wehking J, Van Dorn B, Sarkar S, Laager V, Gerritse B, Laechelt A, Butler J; ALLEVIATE-HF Phase I Investigators. Personalized Intervention Strategy Based on a Risk Score Generated From Subcutaneous Insertable Cardiac Monitor: Results From Phase 1 of ALLEVIATE-HF. J Am Heart Assoc. 2024 Oct 15;13(20):e035501. doi: 10.1161/JAHA.124.035501. Epub 2024 Oct 11.
PubMed 39392161
Zile MR, Kahwash R, Sarkar S, Koehler J, Zielinski T, Mehra MR, Fonarow GC, Gulati S, Butler J. A Novel Heart Failure Diagnostic Risk Score Using a Minimally Invasive Subcutaneous Insertable Cardiac Monitor. JACC Heart Fail. 2024 Jan;12(1):182-196. doi: 10.1016/j.jchf.2023.09.014. Epub 2023 Nov 8.
PubMed 37943225

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Recruiting
Barostim-Enabled NEurohormonal Intervention For Improving Treatment of Heart Failure
Heart Failure, Heart Failure NYHA Class II
Recruiting
PrEcision Pacing in HFpEF: the PEP-HFpEF Trial
Heart Failure and Preserved Ejection Fraction, Heart Failure New York Heart Association Class III
Active, not recruiting
Neural Cardiac Therapy for Heart Failure Study (NECTAR-HF)
Heart Failure, Congestive Heart Failure
Recruiting
NORM-HF Pivotal Study
Heart Failure, NYHA Class III Heart Failure
Not yet recruitingObservational study
Dietary Tracking in Heart Failure
Heart Failure, NYHA Class II Heart Failure

All Heart Failure NYHA Class II trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure
ClinicalTrials.gov ID: NCT04452149
Acronym / sponsor ID: ALLEVIATE-HF / ALLEVIATE-HF
Conditions: Heart Failure NYHA Class II, Heart Failure NYHA Class III
Keywords: Heart Failure, Insertable Cardiac Monitor
Study type: Interventional
Recruitment status: Completed
Enrolment: 826 participants (actual)
Lead sponsor: Medtronic Cardiac Rhythm and Heart FailureIndustry (pharma, biotech, devices)
Study start: 3 Sep 2020 (actual)
Primary completion: 2 Jun 2025 (actual)
Study completion: 2 Jun 2025 (actual)
First posted: 30 Jun 2020 (actual)
Results: Posted 26 Aug 2026

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 4
Model description: Following Reveal LINQ™ device insertion, subjects will be randomly allocated in a blinded fashion in a 1:1 ratio to either the observation arm or the intervention arm. Subjects in the observation arm will start with an observational period of 13 months and then transition to the intervention arm for the remainder of their participation in the study.

Arm	Type	Receives
Observation Arm	Placebo comparator	Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware downloadSubjects will receive a Reveal LINQ™ Insertable Cardiac Monitor with an investigational ALLEVIATE-HF RAMware download, and will be managed per standard of care for heart failure management without visibility to the heart failure sensor data. Subjects will transition to the intervention arm after 13 months.
Intervention Arm	Experimental	Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download, Other: Medication interventionSubjects will receive a Reveal LINQ™ Insertable Cardiac Monitor with an investigational ALLEVIATE-HF RAMware download, and will be managed using an integrated device diagnostic-based risk stratification algorithm combined with a clinical medication plan.
Additional Participants Included Only in Safety Set	Other	Other: Not Randomized to Device or Medication InterventionParticipants who were only randomized to an earlier version of the Clinical Investigational Plan and were only analyzed for the secondary safety outcome. The randomization under the previous version was not pertinent to the primary or secondary outcomes, and thus are combined into one group for the main analysis.
Participants Not Included in Study Analyses	Other	Other: Not Randomized to Device or Medication InterventionPatients who were, with one exception, exited prior to randomization. The exception was a patient who was ineligible for the study analyses due to being enrolled under the previous version of the investigational plan with a pre-existing LINQ device, and thus ineligible for the Analysis Set or the Safety Set.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Patient has NYHA Class II or III heart failure per most recent assessment, irrespective of left ventricular ejection fraction (LVEF)
Patient has documented recent history of symptomatic heart failure, defined as meeting any one of the following three criteria: 1. Hospital admission with primary diagnosis of HF within the last 12 months, OR 2. Intravenous HF therapy (e.g. IV diuretics/vasodilators) or ultrafiltration within the last 6 months, OR 3. Patient had the following BNP/NT-proBNP within the last 3 months: If LVEF ≥ 50%, then BNP> 150 pg/ml or NT-proBNP > 450 pg/ml OR If LVEF is <50%, then BNP> 300 pg/ml or NT-proBNP > 900 pg/ml
Patient is willing and able to comply with the protocol, including LINQ ICM insertion, CareLink transmissions (including adequate connectivity), study visits and remote care directions.
Patient is 18 years of age or older.
Patient has a life expectancy of 12 months or more.

Key exclusion criteria (19 listed)

Patient is currently implanted with a cardiovascular implantable electronic device (CIED) (e.g. ICM, pacemaker, ICD, CRT-D or CRT-P device) or hemodynamic monitor.
Patient is receiving temporary or permanent mechanical circulatory support.
Patient had MI or PCI/CABG within past 90 days.
Patient has had a heart transplant, or is currently on heart transplant list.
Patient has severe valve stenosis on echocardiogram.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware downloadReveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.	Device	Intervention Arm, Observation Arm
Medication interventionRisk status guided medication intervention.	Other	Intervention Arm
Not Randomized to Device or Medication InterventionNo intervention was assigned due to not being randomized under the final version of the investigational plan	Other	Additional Participants Included Only in Safety Set, Participants Not Included in Study Analyses

Primary outcome

Safety of Patient Management Pathway - Proportion of PRN Medication Interventions With Associated PRN Medication Intervention Related Serious Adverse Events (SAEs)
Time frame: From 6 weeks after installation of RAMware through the duration of follow-up for Intervention arm subjects, and from the conclusion of the 13-month randomized period through the duration of follow-up for Observation arm subjects, up to 3 years.
The proportion of PRN medication interventions with one or more associated medication intervention related serious SAEs as adjudicated by the independent Clinical Events Committee will be evaluated. The objective is met when the point estimate for the event rate is less than or equal to 0.05 (5%).
Efficacy of Patient Management Pathway - Hierarchical Composite of Cardiovascular Death, Heart Failure (HF) Events, Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) and Change in Six-minute Walk Test Distance
Time frame: From 6 weeks after installation of RAMware to the end of the 13-month randomized period.
The win ratio for the hierarchical composite endpoint, defined as Intervention arm wins divided by Observation arm wins, will be evaluated using the Finkelstein-Schoenfeld test. Analysis will include subjects with at least one "high" HF risk status during the analysis period (i.e. between 42 and 395 days post-randomization, to exclude the 6-weeks after the installation of RAMware and include data occurring prior to the 13-month timepoint). HF event, as adjudicated by the independent Clinical Events Committee, is defined as an event requiring invasive HF therapy (e.g. IV or subcutaneous diuretics/vasodilators/inotropes) or ultrafiltration, and includes events with or without hospitalization. The Clinical Composite Score is used as KCCQ measure. The primary efficacy objective is met when the win ratio is significantly larger than 1.0, with a p-value below 0.05.

2 secondary outcomes

Safety of Reveal LINQ™ System and Procedure - Percentage of Subjects With Freedom From Experiencing System or Procedure Related Serious Adverse Events
Time frame: From time of Reveal LINQ™ device insertion attempt to 6 months post insertion attempt.
Efficacy of Patient Management Pathway - Hierarchical Composite of Cardiovascular Death, HF Events, Change in KCCQ, Change in Six-minute Walk Test Distance, and Change in Device-measured Activity and Night Heart Rate
Time frame: From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Results and safety

Results posted to the registry on 26 Aug 2026, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Observation Arm	354	287
Intervention Arm	357	283
Additional Participants Included Only in Safety Set - Observation Arm	41	16
Additional Participants Included Only in Safety Set - Intervention Arm	18	6
Additional Participants Included Only in Safety Set - Not Randomized	1	0
Participants Not Included in Analyses	55	0

Primary outcome: Safety of Patient Management Pathway - Proportion of PRN Medication Interventions With Associated PRN Medication Intervention Related Serious Adverse Events (SAEs)

Time frame: From 6 weeks after installation of RAMware through the duration of follow-up for Intervention arm subjects, and from the conclusion of the 13-month randomized period through the duration of follow-up for Observation arm subjects, up to 3 years.. Number (95% Confidence Interval). Unit: Proportion of Interventions with SAEs

Measure	PRN Medication Interventions n = 241
Value	0.00322 (0.00104 to 0.00987)

Population analysed: The outcome measure is based on number of PRN medication interventions and not number of subjects with interventions nor total number of subjects in the study. To qualify for a PRN intervention a subject must have been randomized to the Intervention arm and experienced a "high" heart failure risk status during the efficacy analysis period, or been randomized to either treatment arm and experienced a "high" risk status after continuing to the post-randomization prolonged follow-up period.

Primary outcome: Efficacy of Patient Management Pathway - Hierarchical Composite of Cardiovascular Death, Heart Failure (HF) Events, Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) and Change in Six-minute Walk Test Distance

Time frame: From 6 weeks after installation of RAMware to the end of the 13-month randomized period.. Number (95% Confidence Interval). Unit: Win Ratio

Measure	Efficacy Analysis Set n = 426
Value	0.79 (0.62 to 1.01)

Efficacy Analysis Set: Ratio of Intervention arm wins to losses: 0.79 (95% CI 0.62 to 1.01), p = 0.064, Finkelstein-Schoenfeld test

Population analysed: Includes subjects who experienced a "high" heart failure risk status during the analysis period, defined as from 6 weeks after installation of RAMware to the end of the 13-month randomized period.

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: AEs were collected from time of informed consent through duration of study participation. Events that occurred during 13-month randomized period are reported by study arm. Events that occurred during prolonged follow-up beyond 13 months (up to 3 years) in randomized subjects are combined into one group. AEs collected through duration of participation are reported for subjects who only contributed to analysis of the secondary safety outcome, and for those who were not included in any analysis.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Observation Arm - Analysis Period	218 of 354 (61.6%)	74 of 354 (20.9%)	17 of 354
Intervention Arm - Analysis Period	218 of 357 (61.1%)	91 of 357 (25.5%)	22 of 357
Prolonged Follow-up Post Analysis Period	173 of 436 (39.7%)	59 of 436 (13.5%)	16 of 436
Additional Participants Included Only in Safety Set	49 of 60 (81.7%)	25 of 60 (41.7%)	14 of 60
Participants Not Included in Analyses	11 of 55 (20%)	1 of 55 (1.8%)	6 of 55

Limitations and caveats (from the sponsor): Effects of the protocolized intervention implementation were primarily limited by three distinct factors. First, the accuracy of the risk algorithm, which in this trial demonstrated a sensitivity of 69.1%. Second, the appropriateness of the protocol, which included restrictive rule-out criteria that withheld intervention in 53% of "high" risk status instances. Third, operational execution, as delays and clinician judgment led to only 31% of eligible alerts being treated within two weeks.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Aug 2026.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 42201288Butler J, Kahwash R, Khan MS, Zhang D, Dukes JW, Reddy M, Basuray A, Gharib E, Gerritse B, Laechelt A, Wehking J, Sarkar S, Van Dorn B, Patel N, Laager V, Zile MR; ALLEVIATE-HF Investigators. Risk-Based Nurse-Managed Personalized Heart Failure Interventions: The ALLEVIATE-HF Trial. J Am Coll Cardiol. 2026 Jun 30;87(25):3592-3607. doi: 10.1016/j.jacc.2026.03.075. Epub 2026 May 27.
Derived from this study: PubMed 42201276Kahwash R, Butler J, Khan MS, Zhang D, Dukes J, Reddy M, Kaplan RM, Amin A, Kanwar R, Sarkar S, Laager V, Wehking J, Van Dorn B, Gerritse B, Patel N, Laechelt A, Zile MR; ALLEVIATE-HF Investigators. Arrhythmia Burden and Clinical Responses Under Continuous Monitoring in Heart Failure: Observations From the ALLEVIATE-HF Trial. J Am Coll Cardiol. 2026 Jun 30;87(25):3611-3628. doi: 10.1016/j.jacc.2026.03.174. Epub 2026 May 27.
Derived from this study: PubMed 39392161Kahwash R, Zile MR, Chalasani P, Bertolet B, Gravelin L, Khan MS, Wehking J, Van Dorn B, Sarkar S, Laager V, Gerritse B, Laechelt A, Butler J; ALLEVIATE-HF Phase I Investigators. Personalized Intervention Strategy Based on a Risk Score Generated From Subcutaneous Insertable Cardiac Monitor: Results From Phase 1 of ALLEVIATE-HF. J Am Heart Assoc. 2024 Oct 15;13(20):e035501. doi: 10.1161/JAHA.124.035501. Epub 2024 Oct 11.
Derived from this study: PubMed 37943225Zile MR, Kahwash R, Sarkar S, Koehler J, Zielinski T, Mehra MR, Fonarow GC, Gulati S, Butler J. A Novel Heart Failure Diagnostic Risk Score Using a Minimally Invasive Subcutaneous Insertable Cardiac Monitor. JACC Heart Fail. 2024 Jan;12(1):182-196. doi: 10.1016/j.jchf.2023.09.014. Epub 2023 Nov 8.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Javed Butler, MD principal investigator

Baylor Scott and White Health

53 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 19 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 53 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 26 Aug 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety of Patient Management Pathway - Proportion of PRN Medication Interventions With Associated PRN Medication Intervention Related Serious Adverse Events (SAEs) (time frame: From 6 weeks after installation of RAMware through the duration of follow-up for Intervention arm subjects, and from the conclusion of the 13-month randomized period through the duration of follow-up for Observation arm subjects, up to 3 years.). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04452149, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Aug 2026.