Heart Failure NYHA Class II, Heart Failure NYHA Class III
Conditions
Keywords
Heart Failure, Insertable Cardiac Monitor
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.
Interventions
DEVICEReveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download
Reveal LINQ™ Insertable Cardiac Monitor with investigational ALLEVIATE-HF RAMware download.
OTHERMedication intervention
Risk status guided medication intervention.
OTHERNot Randomized to Device or Medication Intervention
No intervention was assigned due to not being randomized under the final version of the investigational plan
Sponsors
Medtronic Cardiac Rhythm and Heart Failure
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, 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.
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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety of Patient Management Pathway - Proportion of PRN Medication Interventions With Associated PRN Medication Intervention Related Serious Adverse Events (SAEs) | 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 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. | 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%. |
| 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. | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJaved Butler, MD
Baylor Scott and White Health
Participant flow
Recruitment details
Subjects were enrolled over an approximately four-year period at 53 investigational sites in the U.S., with first enrollment occurring on 03-SEP-2020 and last enrollment on 29-AUG-2024. Patients were screened by the investigational site team to ensure they met all inclusion and none of the exclusion criteria prior to study enrollment. Subjects were considered enrolled when informed consent was obtained, which was required prior to any study related procedures occurring.
Pre-assignment details
Enrolled subjects were implanted with a Reveal LINQ™ Insertable Cardiac Monitor (ICM) with an investigational ALLEVIATE-HF RAMware download, or received this RAMware download if enrolled with a pre-existing Reveal LINQ device. Subjects were randomized following successful RAMware download.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 70.4 Years STANDARD_DEVIATION 12 |
| LVEF >= 50% | 237 Participants |
| Race/Ethnicity, Customized American Indian or Alaska Native | 4 Participants |
| Race/Ethnicity, Customized Asian | 6 Participants |
| Race/Ethnicity, Customized Black or African American | 44 Participants |
| Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race/Ethnicity, Customized Not reported | 0 Participants |
| Race/Ethnicity, Customized Other | 0 Participants |
| Race/Ethnicity, Customized White | 695 Participants |
| Sex: Female, Male Female | 371 Participants |
| Sex: Female, Male Male | 25 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk |
|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 17 / 354 | 22 / 357 | 16 / 436 | 14 / 60 | 6 / 55 |
| other Total, other adverse events | 74 / 354 | 91 / 357 | 59 / 436 | 25 / 60 | 1 / 55 |
| serious Total, serious adverse events | 218 / 354 | 218 / 357 | 173 / 436 | 49 / 60 | 11 / 55 |
Outcome results
None listed