Lowering some guideline heart-failure medicines in people whose heart function has recovered
A Prospective, Randomized, Controlled Clinical Pilot Trial Investigating the Partial Down-titration of Guideline-directed Medical Therapy in Patients With Heart Failure in Remission.
This trial will test whether carefully lowering some guideline heart-failure medicines is safe for adults whose reduced-ejection-fraction heart failure has recovered to normal levels.
Quick facts
| Phase | Phase 4 |
|---|---|
| Study type | Interventional |
| Enrollment | 100 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ziekenhuis Oost-Limburg Academic / other |
| Locations | 1 site (Genk) |
| Trial ID | NCT07513883 on ClinicalTrials.gov |
What this trial studies
Adults who previously had heart failure with reduced ejection fraction but now show recovered left ventricular function and low NT-proBNP are invited to participate. Participants either undergo a planned partial down-titration of their guideline-directed heart-failure medications or continue their current regimen, with regular follow-up visits including imaging and biomarker checks. The protocol requires prior stability on at least three guideline therapies at maximally tolerated doses for six months before enrollment. Outcomes will focus on heart function, symptoms, and biomarkers to detect any relapse.
Who should consider this trial
Good fit: Ideal candidates are adults (≥18) who had HFrEF (LVEF <40%) but now have normalized LVEF (≥50%), normal LV volumes, NT-proBNP <250 pg/mL, no residual functional limitations, and have been stable on at least three guideline heart-failure drugs for six months.
Not a fit: Patients with ongoing reduced ejection fraction, recent heart-failure events, elevated NT-proBNP, severe kidney disease, unstable medication doses, or who are on fewer than three guideline therapies are unlikely to benefit and may be excluded for safety.
Why it matters
Potential benefit: If successful, the approach could allow some patients to safely reduce medication burden, lower side effects, and cut costs while maintaining heart recovery.
How similar studies have performed: Small prior trials and observational studies (for example TRED-HF) have tested withdrawal approaches and found a substantial relapse risk in some patients, so this area has limited but important prior data rather than being entirely untested.
Eligibility criteria
Show full inclusion / exclusion criteria
Inclusion Criteria: * 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. Exclusion Criteria: * 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.
Where this trial is running
Genk
- Ziekenhuis Oost-Limburg — Genk, Belgium (Recruiting)
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.