Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure

Study Overview
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Brief Summary
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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
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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 700 subjects at up to 60 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.

Official Title
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Algorithm Using LINQ Sensors for Evaluation And Treatment of Heart Failure

Conditions
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Heart Failure NYHA Class II, Heart Failure NYHA Class III

Intervention / Treatment
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* Device: Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download
* Other: Medication intervention


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Observation Arm<br>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<br>* Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.<br>|
| Experimental: Intervention Arm<br>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<br>* Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.<br>Other: Medication intervention<br>* Risk status guided medication intervention.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of patient management pathway - Proportion of medication interventions with associated medication intervention related serious adverse events | The proportion of medication interventions with one or more associated medication intervention related SAEs will be evaluated. | Up to 3 years | 
| 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 | Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method, including subjects with at least one high heart failure risk status. | Follow-up duration at endpoint analysis ranges from a minimum of 7 to a maximum of 13 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety of Reveal LINQ™ system and procedure - Percentage of subjects experiencing system or procedure related serious adverse events | Freedom from Reveal LINQ™ system and procedure related serious adverse events at 6 months will be evaluated. | Up to 6 months post Reveal LINQ™ device insertion attempt | 
| 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 | Treatment and Control groups will be compared using the Finkelstein-Schoenfeld method, including subjects with at least one high heart failure risk status. | Follow-up duration at endpoint analysis ranges from a minimum of 7 to a maximum of 13 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Heart Failure, Insertable Cardiac Monitor