NCT04853758: ANSWER-HF

Angiotensin Receptor-Neprilysin Inhibition in Chagas Cardiomyopathy With Reduced Ejection Fraction: ANSWER-HF.

Recruiting now Phase 3 Last updated 4 April 2024

What this trial tests

Phase 3 trial testing Sacubitril / Valsartan Oral Tablet [Entresto] in Chagas Cardiomyopathy in 200 participants. Currently enrolling.

Timeline

6 May 2021

Primary endpoint
1 December 2024

1 December 2024

Quick facts

Lead sponsor	University of Sao Paulo General Hospital
Phase	Phase 3
Status	Recruiting now
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	triple
Primary purpose	treatment
Enrollment	200
Start date	6 May 2021
Primary completion	1 December 2024
Estimated completion	1 December 2024
Sites	1 location across Brazil

Drugs / interventions tested

• Sacubitril / Valsartan Oral Tablet [Entresto] — full drug profile →
• Enalapril (enalapril) — full drug profile →

Conditions studied

• Chagas Cardiomyopathy — all drugs for Chagas Cardiomyopathy →

Sponsor

University of Sao Paulo General Hospital

Who can join

18 and older, any sex, with Chagas Cardiomyopathy. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Chagas disease is considered by the World Health Organization (WHO) as one of the most neglected tropical diseases in the world, having relevance in many Latin America countries. In addition, it already affects North America, Europe, Asia and Oceania. Some studies suggest that chagasic heart failure has a worse prognosis, with up to 50% shorter survival than other etiologies. The PARADIGM-HF (Prospective Comparison of Angiotensin Receptor Blocker-Neprilysin Inhibitor With Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure) study showed 20% reduction in mortality comparing sacubitril/valsartan with the standard treatment with ACE (angiotensin converting enzyme) inhibitors. In the scenario of chagasic cardiomyopathy, a post hoc analysis of PARADGIM-HF was reported on 113 patients. Reduced risk of cardiovascular death or hospitalization for HF was noted in the group treated with sacubitril/valsartan. Attention was drawn the study's limitations that included the small number of patients and reduced statistical power. Therefore, the benefit of this new class remains uncertain in heart failure due to Chagas cardiomyopathy. The ANSWER-HF Trial will be a clinical, randomized, single-center, prospective, double-blind, controlled study. It will include 200 consecutive participants with Chagas cardiomyopathy and left ventricular ejection fraction less than 40% randomized independently. The objective of this study is to evaluate the benefit of sacubitril/valsartan compared with enalapril in patients with heart failure due to Chagas cardiomyopathy, with reduced ejection fraction. The primary endpoint of the study is the change of left ventricular ejection fraction determined by transthoracic echocardiography. Secondary endpoints include: assessment of ventricular arrhythmias; evaluation of functional class; assessment of functional capacity; assessment of ventricular remodeling; and evaluation of biomarkers. The patients will be followed for 6 months after treatment start. All patients will be undergone to Doppler Echocardiography, 24-hour Holter, 6-minute walk test, Biochemical and hematological exams and Biomarkers at the baseline and after 6 months.

Publications & conference data

2 peer-reviewed publications reference this trial (live from Europe PMC):

1. Clinical trials for Chagas disease: etiological and pathophysiological treatment.
   Gonzaga BMS, Ferreira RR, Coelho LL, Carvalho ACC, et al · · 2023 · cited 10× · PMID 38188583 · DOI 10.3389/fmicb.2023.1295017
2. Sacubitril-Valsartan vs Enalapril in Heart Failure Due to Chagas Disease: Primary Results of ANSWER-HF Randomized Trial.
   Madrini V, Souza PVR, Fernandes F, Ianni BM, et al · · 2026 · cited 1× · PMID 41396086 · DOI 10.1016/j.jacc.2025.10.053