Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure (ALLEVIATE-HF)

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure NYHA Class II; Heart Failure NYHA Class III
• Intervention / Treatment: Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download; Other: Medication intervention; Other: Not Randomized to Device or Medication Intervention

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.

• Study Type: Interventional
• Enrollment (Actual): 826
• Phase: Not Applicable

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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).
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Observation Arm; 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.	Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download; Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.
Experimental: Intervention Arm; 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.	Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download; Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.; Other: Medication intervention; Risk status guided medication intervention.
Other: Additional Participants Included Only in Safety Set; 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.	Other: Not Randomized to Device or Medication Intervention; No intervention was assigned due to not being randomized under the final version of the investigational plan
Other: Participants Not Included in Study Analyses; 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.	Other: Not Randomized to Device or Medication Intervention; No intervention was assigned due to not being randomized under the final version of the investigational plan

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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%).	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.	From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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%.	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.	From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Principal Investigator: Javed Butler, MD, Baylor Scott and White Health

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): September 3, 2020
• Primary Completion (Actual): June 2, 2025
• Study Completion (Actual): June 2, 2025

Study Registration Dates

• First Submitted: June 24, 2020
• First Submitted That Met QC Criteria: June 26, 2020
• First Posted (Actual): June 30, 2020

Study Record Updates

• Last Update Posted (Actual): August 26, 2026
• Last Update Submitted That Met QC Criteria: August 3, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Insertable Cardiac Monitor
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: ALLEVIATE-HF

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No