About AIM HIGHer
The AIM HIGHer Clinical Trial is a prospective, multicenter, randomized, quadruple-blind, sham-controlled, two-part embedded trial of the safety and efficacy of CCM® therapy delivered by the Optimizer® Smart Mini in subjects with heart failure and an LVEF ≥40% and ≤60%. Subjects will be enrolled at approximately 150 sites in the US.
All subjects will undergo screening and baseline testing. All eligible subjects will be implanted with the Optimizer system.
Subjects will be randomized in a 2:1 ratio to either CCM therapy ON (CCM therapy group) or CCM therapy OFF (Sham group). The trial will be blinded to the treatment assignment of the device for 18-months. Subjects in the Sham group will have CCM therapy turned ON after completing the 18-month study visit. Subjects enrolled during Part I (450 subjects) of the trial will continue follow-up through the end of Part II (up to an additional 1,050 subjects) and contribute data to both parts of the trial. Each part of the trial is distinguished by a separate scientific purpose. The specific purpose of each part is:
Part I – Establish safety and effectiveness based on functional capacity and health status.
Part II – Establish safety and effectiveness based on clinical outcome data.
Part I - Primary Efficacy Objectives
- Demonstrate that CCM therapy improves functional capacity in subjects with symptomatic heart failure with LVEF ≥40% and ≤60%. Compare the changes in functional capacity, as measured by the 6-minute walk distance (6MWD), from baseline to 6-months following the randomization date between the two study groups.
- Demonstrate that CCM therapy improves health status in subjects with symptomatic heart failure with LVEF ≥40% and ≤60%. Compare the changes in health status, as measured by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Clinical Summary Score (CSS), from baseline to 6-months following the randomization date between the two study groups.
Part I - Primary Safety Objective
- Demonstrate that CCM therapy is safe in subjects with symptomatic heart failure with LVEF ≥40% and ≤60%. Compare the composite incidence of Optimizer device-related and procedure-related SAEs (complications) for available data collected from implant to 12 months after the Optimizer implantation procedure to a performance goal of 75% free of complications.
Part II – Primary Objective
Demonstrate that CCM therapy improves a composite of morbidity, mortality, and health status outcomes. Comparison of a hierarchical composite endpoint of the following between the two study groups:
- Cardiovascular death at 18 months
- Heart failure hospitalization at 18 months
- Urgent heart failure visits requiring IV treatment at 18 months
- Change in KCCQ CSS at 12 months
2. Male or non-pregnant female, 21 years or older;
3. Diagnosed with symptomatic heart failure;
4. LVEF ≥40% and ≤60% (as assessed by echo core lab);
5. Heart failure hospitalization within 12 months prior to study consent OR Urgent heart failure visit requiring IV therapy during the six months prior to study consent;
6. Elevated NT-proBNP levels, >200 pg/ml for subjects without atrial tachyarrhythmia (AT) or > 600 pg/ml for subjects in AT OR Elevated BNP levels, > 75 pg/ml for subjects without atrial tachyarrhythmia (AT) or > 225 pg/ml for subjects in AT;
7. Subjects must be on a stable, scheduled oral loop diuretic treatment (not only PRN) for at least 30 days prior to study consent, unless documented allergy.
- Resting heart rate <50 or >110 bpm;
- Resting systolic blood pressure <100 or >160 mmHg;
- BMI greater than 40
- Any moderate or severe valvular stenotic disease or any severe valvular regurgitation;
- Mechanical tricuspid valve;
- Complex congenital heart disease;
- Exercise tolerance limited by a condition other than heart failure that, in the opinion of the investigator, contributes significantly to the primary symptoms of shortness of breath and/or exercise intolerance;
- Unable to walk at least 100 meters or walks more than 450 meters during a 6MWT;
- A KCCQ CSS score higher than 85;
- Hypertrophic, infiltrative/restrictive, or inflammatory cardiomyopathy as documented in the medical record;
- Unstable angina pectoris within 30 days prior to study consent;
- Acute, decompensated heart failure requiring IV therapy or ultrafiltration within 30 days prior to consent, in the hospital or an outpatient setting;
- Receiving cardiac resynchronization therapy (CRT);
- Scheduled for cardiac surgery or a percutaneous cardiac intervention (PCI) or have undergone cardiac surgery within 90 days or a PCI procedure within 30 days prior to study consent;
- Myocardial infarction within 90 days prior to study consent;
- Prior heart transplant or ventricular assist device;
- Planning to become pregnant during the study;
- Dialysis (permanent) or GFR <20 ml/min/1.73m2;
- Participating in another investigational study;
- Currently undergoing active chemotherapeutic and/or radiation treatment for cancer or has a history of chemotherapy during the 2-year period prior to study consent;
- Expected lifespan of less than 18 months from time of study consent;