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

• ClinicalTrials.gov Identifier: NCT04452149
• Recruitment Status: Recruiting
• First Posted: June 30, 2020
• Last Update Posted: May 9, 2024
• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Information provided by (Responsible Party): Medtronic Cardiac Rhythm and Heart Failure

Tracking Information

• First Submitted Date: June 24, 2020
• First Posted Date: June 30, 2020
• Last Update Posted Date: May 9, 2024
• Actual Study Start Date: September 3, 2020
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: September 2, 2021)

• Safety of patient management pathway - Proportion of medication interventions with associated medication intervention related serious adverse events [ Time Frame: Up to 3 years ]
  The proportion of medication interventions with one or more associated medication intervention related SAEs will be evaluated.
• Efficacy of patient management pathway - Hierarchical composite of Cardiovascular death, HF events, change in Kansas City Cardiomyopathy Questionnaire and change in six-minute walk test distance [ Time Frame: Follow-up duration at endpoint analysis ranges from a minimum of 7 to a maximum of 13 months ]
  Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method, including subjects with at least one "high" heart failure risk status.

Original Primary Outcome Measures (submitted: June 26, 2020)

Safety of the patient management pathway (i.e. proportion of medication interventions with associated medication intervention related serious adverse events) [ Time Frame: Up to 3 years ]

The proportion of medication interventions with one or more associated medication intervention related SAEs will be evaluated.

Current Secondary Outcome Measures (submitted: September 2, 2021)

• Safety of Reveal LINQ™ system and procedure - Percentage of subjects experiencing system or procedure related serious adverse events [ Time Frame: Up to 6 months post Reveal LINQ™ device insertion attempt ]
  Freedom from Reveal LINQ™ system and procedure related serious adverse events at 6 months will be evaluated.
• Efficacy of patient management pathway - Hierarchical composite of Cardiovascular death, HF events, change in Kansas City Cardiomyopathy Questionnaire, change in six-minute walk test distance, and change in device-measured activity and night heart rate [ Time Frame: Follow-up duration at endpoint analysis ranges from a minimum of 7 to a maximum of 13 months ]
  Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method, including subjects with at least one "high" heart failure risk status.

• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure
• Official Title: Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure
• 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.
• 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
• Study Phase: Not Applicable

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention 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 (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

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.

Primary Purpose: Treatment

Condition

• Heart Failure NYHA Class II
• Heart Failure NYHA Class III

Intervention

• 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.

Study Arms

• 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.
  Intervention: Device: 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.
  Interventions:

  • Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download
  • Other: Medication intervention

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: March 25, 2024): 900
• Original Estimated Enrollment (submitted: June 26, 2020): 300
• Estimated Study Completion Date: April 2025
• Estimated Primary Completion Date: April 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

Contact: Aimee Laechelt; (+1-763) 267-8748; aimee.a.laechelt@medtronic.com

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT04452149
• Other Study ID Numbers: ALLEVIATE-HF
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Medtronic Cardiac Rhythm and Heart Failure
• Original Responsible Party: Same as current
• Current Study Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: Javed Butler, MD; Baylor Scott and White Health

• PRS Account: Medtronic Cardiac Rhythm and Heart Failure
• Verification Date: April 2024