Assessment of CCM in HF With Higher Ejection Fraction

Официальное название

Assessment of Implantable CCM in the Heart Failure Group With Higher Ejection Fraction

Обзор

The AIM HIGHer Clinical Trial will evaluate the safety and efficacy of Cardiac Contractility Modulation (CCM) therapy in patients with heart failure with LVEF ≥40% and ≤70%.

Подробное описание

The AIM HIGHer Clinical Trial is a prospective, multi-center, randomized, quadruple-blind, sham-controlled, two-part embedded trial of the safety and efficacy of CCM therapy delivered via the OPTIMIZER Smart Mini System in subjects with heart failure and an LVEF ≥40% and ≤70%. Subjects will be enrolled at approximately 150 sites in the US and 75 sites OUS.

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 ON (CCM group) or to CCM 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 turned ON after completion of 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) 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.

Вмешательства

• Устройство Cardiac Contractility Modulation Therapy via OPTIMIZER™ Smart Mini System
  The OPTIMIZER™ Smart Mini System will be implanted and CCM will be programmed ON for the first 18 months (blinded phase). CCM therapy will be programmed to deliver 7 one-hour phases of CCM therapy that are distributed equally over every 24-hour period. CCM will remain on following completion of the 18-month visit.
• Устройство OPTIMIZER™ Smart Mini System
  The OPTIMIZER™ Smart Mini System will be implanted and CCM will be programmed OFF for the first 18 months (blinded phase). CCM will be turned on following completion of the 18-month visit.

Первичные конечные точки

• Part 1 Efficacy Endpoint - Change in 6-minute walk distance (6MWD) from baseline to 6 months. [Срок оценки: 6 months]
• Part 1 Efficacy Endpoint - Change in the health status from baseline to 6 months as assessed by the Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ CSS). [Срок оценки: 6 months]
• Part 1 Safety Endpoint - The incidence of Optimizer device- or procedure-related complications within the first 12 months after implant [Срок оценки: 12 months]
• Part 2 Endpoint - The hierarchical composite of mortality, morbidity, and health status outcomes (KCCQ CSS). [Срок оценки: 18 months]

Критерии участия

Критерии включения

• Signed and dated informed consent form;
• Male or non-pregnant female, 18 years or older;
• Diagnosed with symptomatic heart failure;
• LVEF ≥40 and ≤70% (as assessed by site echo);
• A. Heart failure hospitalization within 12 months prior to study consent OR an urgent heart failure visit requiring IV therapy within 6 months prior to study consent OR B. If there is no heart failure hospitalization within 12 months prior to study consent OR an urgent heart failure visit requiring IV therapy within 6 months prior to study consent, an elevated BMI-adjusted natriuretic peptide value must be achieved (Refer to Table 1 in Section 9.2.6)
• Subjects must meet one of the following conditions:

• Have stable, scheduled oral loop diuretic treatment (not just PRN) for a minimum of 30 days before providing study consent unless there is a documented allergy or intolerance.
• Eligibility for enrollment is maintained for patients on an SGLT2 inhibitor without prescribed concurrent standing loop diuretic therapy if investigators provide instructions for a flexible PRN diuretic regimen (deemed appropriate by the clinician in response to symptoms or weight gain) Note: Stable is defined as no more than a 100% increase or 50% decrease in dose within the last 30 days. A one-time hold of diuretic dosing for 24 hours during the 30-day period is allowed and not an exclusionary event.

Критерии исключения

• Resting ventricular rate <50 or >110 bpm;
• Resting systolic blood pressure <100 or ≥160 mmHg;
• BMI greater than 46
• Any 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 CCS score higher than 85;
• Hypertrophic, infiltrative/restrictive or inflammatory cardiomyopathy;
• 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); NOTE: Subjects with active/ongoing cardiac resynchronization therapy (CRT) implanted more than one year ago are eligible for inclusion if they are currently classified as NYHA class III or higher.
• Scheduled for a 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 <15 ml/min/1.73m2;
• Participating in another investigational drug or device study that may interfere with the interpretation of study data;
• 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;
• Unable to follow through study protocol for any reasons in the investigator's judgement.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

США · 105 центров

• Grandview Medical Group Research, LLC — Birmingham
• CardioVascular Associates of Mesa — Mesa
• Chan Heart Rhythm Institute — Mesa
• Southwest Cardiovascular Associates — Mesa
• Arizona Heart Rhythm — Phoenix
• Cardiovascular Consultants, Ltd — Phoenix
• HonorHealth — Scottsdale
• Pima Heart and Vascular — Tuscon
• … и ещё 97 центров

Публикации

• Abraham WT, Kuck KH, Goldsmith RL, Lindenfeld J, Reddy VY, Carson PE, Mann DL, Saville B, Parise H, Chan R, Wiegn P, Hastings JL, Kaplan AJ, Edelmann F, Luthje L, Kahwash R, Tomassoni GF, Gutterman DD, Stagg A, Burkhoff D, Hasenfuss G. A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation. JACC Heart Fail. 2018 Oct;6(10):874-883. doi: 10.1016/j.jchf. PMID 29754812
• Wiegn P, Chan R, Jost C, Saville BR, Parise H, Prutchi D, Carson PE, Stagg A, Goldsmith RL, Burkhoff D. Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study. Circ Heart Fail. 2020 Apr;13(4):e006512. doi: 10.1161/CIRCHEARTFAILURE.119.006512. Epub 2020 Apr 8. PMID 32264716
• Tschope C, Butler J, Farmakis D, Morley D, Rao I, Filippatos G. Clinical effects of cardiac contractility modulation in heart failure with mildly reduced systolic function. ESC Heart Fail. 2020 Dec;7(6):3531-3535. doi: 10.1002/ehf2.13126. Epub 2020 Dec 3. PMID 33274601
• Tschope C, Van Linthout S, Spillmann F, Klein O, Biewener S, Remppis A, Gutterman D, Linke WA, Pieske B, Hamdani N, Roser M. Cardiac contractility modulation signals improve exercise intolerance and maladaptive regulation of cardiac key proteins for systolic and diastolic function in HFpEF. Int J Cardiol. 2016 Jan 15;203:1061-6. doi: 10.1016/j.ijcard.2015.10.208. Epub 2015 Oct 27. No abstract avai PMID 26638055
• Aneeq A, Jan M, Nisar S, Zahid S, Kumari U. Cardiac contractility modulation: A new horizon in the management of heart failure with preserved ejection fraction (HFpEF). Cardiovasc Revasc Med. 2024 Apr;61:110. doi: 10.1016/j.carrev.2023.11.007. Epub 2023 Nov 11. PMID 37980262

Идентификаторы

NCT: NCT05064709 · CA_CP_340

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗