Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure

NCT04452149 | Completed Results DMC FDA Device

• 1 other identifier: ALLEVIATE-HF
• Study Type: interventional
• Target: 826
• Locations: 1 country
• Sites: 53

Brief Summary

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.

Conditions

Heart Failure NYHA Class II; Heart Failure NYHA Class III

Keywords

Heart Failure; Insertable Cardiac Monitor

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (2)

• Safety of Reveal LINQ™ System and Procedure - Percentage of Subjects With Freedom From Experiencing System or Procedure Related Serious Adverse Events

  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

  From 6 weeks after installation of RAMware to the end of the 13-month randomized period.

Study Arms (4)

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.

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.

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.

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.

Other: Not Randomized to Device or Medication Intervention

Interventions

Not Randomized to Device or Medication Intervention OTHER

No intervention was assigned due to not being randomized under the final version of the investigational plan

Additional Participants Included Only in Safety Set; Participants Not Included in Study Analyses

Medication intervention OTHER

Risk status guided medication intervention.

Intervention Arm

Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download DEVICE

Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.

Intervention Arm; Observation Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Medtronic Cardiac Rhythm and Heart Failure: lead

Study Sites (53)

Cardiovascular Associates of Mesa

Mesa, Arizona, 85282, United States

Location

Arrhythmia Research Group

Jonesboro, Arkansas, 72410, United States

Location

Saint Joseph Heritage Healthcare

Mission Viejo, California, 92691, United States

Location

Cardiology Associates Medical Group

Oxnard, California, 93030, United States

Location

Saint Joseph's Medical Center

Stockton, California, 95204, United States

Location

South Denver Cardiology Associates

Littleton, Colorado, 80120, United States

Location

FWD Clinical Research LLC

Boca Raton, Florida, 33486, United States

Location

Bay Area Cardiology Associates PA

Brandon, Florida, 33511, United States

Location

Florida Heart Center

Ft. Pierce, Florida, 34950, United States

Location

Baptist Health

Jacksonville, Florida, 32207, United States

Location

First Coast Cardiovascular Institute PA

Jacksonville, Florida, 32256, United States

Location

Citrus Cardiology Consultants PA

Leesburg, Florida, 34748, United States

Location

Baptist Hospital

Pensacola, Florida, 32501, United States

Location

Northside Hospital

St. Petersburg, Florida, 33709, United States

Location

Tallahassee Research Institute

Tallahassee, Florida, 32308, United States

Location

Memorial Health University Medical Center

Savannah, Georgia, 31404, United States

Location

NorthShore University Health System

Evanston, Illinois, 60201, United States

Location

Carle Foundation Hospital

Urbana, Illinois, 61801, United States

Location

Parkview Health

Fort Wayne, Indiana, 46845, United States

Location

Ascension Medical Group - Saint Vincent

Indianapolis, Indiana, 46260, United States

Location

Iowa Heart Center

West Des Moines, Iowa, 50266, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Saint Elizabeth Healthcare

Edgewood, Kentucky, 41017, United States

Location

Baptist Healthcare System

Louisville, Kentucky, 40207, United States

Location

Norton Healthcare

Louisville, Kentucky, 40217, United States

Location

North Memorial Health Heart &amp; Vascular Center

Robbinsdale, Minnesota, 55422, United States

Location

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Cardiology Associates of North Mississippi

Tupelo, Mississippi, 38801, United States

Location

CHI Health Creighton University Medical Center - Bergan Mercy

Omaha, Nebraska, 68124, United States

Location

Lourdes Cardiology Services

Voorhees Township, New Jersey, 08043, United States

Location

New Mexico Heart Institute PA

Albuquerque, New Mexico, 87102, United States

Location

Columbia University Irving Medical Center/NYPH

New York, New York, 10032, United States

Location

Hudson Valley Heart Center

Poughkeepsie, New York, 12601, United States

Location

Saint Francis Hospital

Roslyn, New York, 11576, United States

Location

Stony Brook University Hospital

Stony Brook, New York, 11794, United States

Location

Cone Health

Greensboro, North Carolina, 27401, United States

Location

Novant Health New Hanover Regional Medical Center

Wilmington, North Carolina, 28401, United States

Location

The Lindner Research Center

Cincinnati, Ohio, 45219, United States

Location

Mount Carmel East

Columbus, Ohio, 43213, United States

Location

OhioHealth Research and Innovation Institute (OHRI)

Columbus, Ohio, 43214, United States

Location

Doylestown Health Cardiology a division of Doylestown Health Physicians

Doylestown, Pennsylvania, 18901, United States

Location

Cardiology Consultants of Philadelphia

Philadelphia, Pennsylvania, 19107, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Prisma Health Midlands

Columbia, South Carolina, 29203, United States

Location

The Stern Cardiovascular Foundation

Germantown, Tennessee, 38138, United States

Location

University of Tennessee Methodist Physicians

Memphis, Tennessee, 38104, United States

Location

Medical City Fort Worth

Fort Worth, Texas, 76104, United States

Location

Tyler Cardiovascular Consultants

Tyler, Texas, 75701, United States

Location

Sentara Norfolk General Hospital

Norfolk, Virginia, 23507, United States

Location

Swedish Medical Center Cherry Hill

Seattle, Washington, 98122, United States

Location

Saint Joseph Medical Center (Tacoma WA)

Tacoma, Washington, 98405, United States

Location

Charleston Area Medical Center (CAMC) Memorial Hospital

Charleston, West Virginia, 25304, United States

Location

West Virginia University

Morgantown, West Virginia, 26506, United States

Location

Related Publications (4)

• 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.

  PMID: 42201288 DERIVED

• 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.

  PMID: 42201276 DERIVED

• 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.

  PMID: 39392161 DERIVED

• 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.

  PMID: 37943225 DERIVED

MeSH Terms

Conditions

Heart Failure

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Limitations and Caveats

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.

Results Point of Contact

• Title: Aimee Laechelt, Clinical Research Specialist
• Organization: Medtronic, Inc.

aimee.a.laechelt@medtronic.com

+1-800-328-2518

Study Officials

• Javed Butler, MD

  Baylor Scott and White Health

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Study site personnel and subjects will remain blinded to the subject's randomization assignment until the 13-month timepoint at which point the subjects will be in the intervention arm for the remainder of their participation regardless of original allocation, or until the time of investigator and/or subject contact in relation to a "high" risk status in an intervention arm subject.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: June 24, 2020
• First Posted: June 30, 2020
• Study Start: September 3, 2020
• Primary Completion: June 2, 2025
• Study Completion: June 2, 2025
• Last Updated: August 26, 2026
• Results First Posted: August 26, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share

Locations

US (53)