The Assessment of Partial Guideline-Directed Medical Therapy Down Titration in Heart Failure in Remission.

Официальное название

A Prospective, Randomized, Controlled Clinical Pilot Trial Investigating the Partial Down-titration of Guideline-directed Medical Therapy in Patients With Heart Failure in Remission.

Обзор

Heart failure (HF) is a chronic condition that is characterized by a weakened and enlarged heart. It typically causes symptoms such as breathlessness and swelling of the legs, and it is a serious illness that shortens life expectancy. In recent years, new medicines have been developed that can improve heart function and help patients with HF live longer. HF patients with reduced heart function typically are recommended to take four different medicines for the rest of their lives. Some patients respond so well to treatment that their heart function and symptoms appear to recover; this is called HF in remission. While the four standard medicines have proven to increase lifespan in patients with heart failure with reduced heart function, it is not known whether they all need to be continued lifelong after recovery of the heart. Current guidelines recommend treating patients lifelong, yet this is based on limited scientific evidence. Lifelong therapy comes with disadvantages: it carries considerable costs for patients and health care systems, causes potential side effects, and makes it harder for patients to keep up with all their other medications. This study will test whether carefully reducing certain HF medicines is safe compared to continuing them. Patients with heart failure in remission will be randomly assigned to either: (1) continue all standard therapies, or (2) gradually reduce medicines to just two per day under close medical supervision. Patients will followed for two years to see whether their heart function remains stable. This will be measured by looking at echograms of the heart (echocardiograms), blood tests, and whether patients experience serious events such as hospitalizations or death. This study will investigate whether partial therapy discontinuation is safe and feasible.

Вмешательства

• Препарат Down-titration
  The intervention involves a 3-month therapy down-titration period, during which the SGLT2 inhibitor and minerolocorticoid receptor antagonist are withdrawn, and the angiotensin receptor-neprilysin inhibitor is replaced by an ACE inhibitor or angiotensin receptor blocker. The drug formulations used per drug class correspond with the ESC guideline recommendations: * ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandolapril (at the maximally tolerated dose, according to the respec
• Препарат Continuation of guideline-directed heart failure therapy
  The comparator involves the continuation of the maximally tolerated dose of guideline-recommended medical therapy (e.g., ACEi/ARB/ARNI, MRA, SGLT2i, and/or beta blocker) the patient is using at the time of screening. The formulations per drug class may differ according to treatment regimen at randomization, but may include: * ARNI: sacubitril/valsartan (at the maximally tolerated dose, according to the respective drug SmPC) * ACE inhibitor: enalapril, lisinopril, ramipril, captopril or trandol

Первичные конечные точки

• Time to first occurrence of recurrent adverse remodeling, significant NT-proBNP increase or all-cause mortality. [Срок оценки: From enrollment to 2 year follow-up]

Вторичные конечные точки (3)

• Time to first occurrence of cardiovascular mortality or heart failure hospitalizations [Срок оценки: From enrollment to 2 year follow-up]
• Change in quality of life [Срок оценки: From enrollment to 2 year follow-up]
• Proportion of patients requiring heart failure therapy re-initiation or intensification for any reason [Срок оценки: From enrollment to 2 year follow-up]

Критерии участия

Критерии включения

• Signed and dated written informed consent prior to randomization
• Age ≥ 18 years
• Prior diagnosis of heart failure with reduced ejection fraction (left ventricular ejection fraction < 40%)
• Heart failure remission (defined as a quantified improvement in LVEF to ≥50% or described as a "normalized" or "recovered" LVEF on echocardiography or cardiac MRI at least 6 months prior; a normal LVESVi and LVEF during screening; no residual functional limitations caused by heart failure; a NT-proBNP < 250 pg/mL during screening)
• Treatment with at least three heart failure therapies (ACE inhibitors, angiotensin-receptor blockers, angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists, or sodium-glucose cotransporter-2 inhibitors), consistent with international heart failure guidelines, at maximally tolerated dose and stable for at least 6 months before screening.

Критерии исключения

• Severe kidney disease: chronic kidney disease with significant albuminuria, defined as an eGFR (creatinine or cystatin C-based using the 2021 CKD-EPI formula) < 60 mL/min/1,73m2 and a urine-albumine creatinine ratio ≥ 200 mg/g, or requiring dialysis, or a history of kidney transplantation.
• Recent major cardiovascular events, including acute coronary syndromes, coronary artery bypass surgery, stroke, or TIA, in the 90 days before screening.
• Uncontrolled hypertension, defined as a systolic blood pressure above 160 mmHg and/or a diastolic blood pressure above 100 mmHg despite three antihypertensive agents, assessed during a 24-hour blood pressure measurement during screening.
• Atrial fibrillation or atrial flutter with a resting heart rate > 110 beats per minute during screening
• Suboptimal biventricular pacing in those treated with cardiac synchronization therapy, defined as a biventricular pacing percentage under 98% during screening.
• Any concomitant current or future class I indication for the use SGLT2i beside heart failure: diabetes mellitus type II with ASCVD, or at least two major risk factors (i.e., obesity, hypertension, smoking, dyslipidemia or albuminuria) during screening.
• Any sustained ventricular arrhythmias in the six months before screening.
• Any untreated valvular heart disease of moderate or greater severity during screening.
• Presence of any other disease with a life expectancy of less than two years.
• Pregnant or lactating women.

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

Простое слепое

Основная цель

Лечение

Центры проведения

Бельгия · 1 центр

• Ziekenhuis Oost-Limburg — Genk

Идентификаторы

NCT: NCT07513883 · Z-2025058

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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