Sacubitril-valsartan in Patients With Heart Failure With Reduced Ejection Fraction From Rural Tanzania

ConditionHeart Failure

Trial statusRecruiting

Trial phasePhase 4

Trial typeInterventional

Biological sexAll

Age18+

SponsorMartin Rohacek

About this trial

Angiotensin-neprilysin inhibitors (ARNI) are beneficial in patients with heart failure with reduced ejection fraction. No study evaluating ARNI has been conducted in sub-Saharan Africa (except South Africa) yet, where heart failure is a major health problem. Before implementing ARNI in Tanzania, a study evaluating the benefit and safety of ARNI in Africans is needed. The aim of this interventional pre-post study is to evaluate the health status of symptomatic patients with heart failure with reduced ejection fraction who are under a chronic heart failure therapy, before and after switching angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) to ARNI. Participants will be recruited at the Heart and Lung Clinic of the St Francis Regional Referral Hospital in Ifakara in rural Tanzania during a study period of 30 months, including 10 months of follow-up. A total of 298 participants will be included. The investigators hypothesize that health status, expressed by the Kansas City Cardiomyopathy Questionnaire summary score and 6-minute walking test, will improve after switching from ACE-inhibitors or ARB to ARNI. In Tanzania, sacubitril/valsartan is registered under the name Uperio®.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Symptomatic heart failure NYHA class II-IV and

Left ventricular ejection fraction (LVEF) ≤40% and

Treatment with an ACE Inhibitor or an ARB, beta-blocker, and spironolactone in recommended dosages for at least 3 months, and

Adherence to this therapy of at least 80%.

Disqualifiers

Pregnancy

Systolic blood pressure of less than 95 mmHg,

eGFR below 30 ml per minute per 1.73 m2 of body-surface area

Serum potassium level of more than 5.4 mmol per liter

Trial design

Design model

Single group

Treatments tested in this trial

Sacubitril / Valsartan Oral Tablet
Drug
A 36-hour wash-out of ACE inhibitors before initiating ARNI will be done, because of a risk of angioedema if ARNI is started without a wash-out period. The ACE inhibitor or ARB will be switched to sacubitril/valsartan 50mg twice daily (24.3 mg sacubitril, 25.7mg valsartan) for two weeks, increased to 100mg twice daily for three weeks, followed by 200mg twice daily

Treatment groups

298 Participants

are divided into 1 treatment group

Group A: Symptomatic adult particiopants with HFrEF, under heart failure therapyOther 1 intervention

Trial outcomes

Primary outcomes

Proportion of participants with an improved health status based on a large (≥10 points) or very large (≥20 points) improvement of the Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score (minimum 0, maximum 100)

Higher scores of the Kansas City Cardiomyopathy Questionnaire summary score indicate better outcome

Time frame

10 months

Secondary outcomes

Kansas City Cardiomyopathy Questionnaire (KCCQ) summary score (minimum 0, maximum 100)

Higher scores of the Kansas City Cardiomyopathy Questionnaire indicate better outcome

Time frame

5 weeks, 2, 4, 6, and 10 months

New York Heart Association (NYHA) classification (minimum I, maximum IV)

Higher classification in the New York Heart Association classification means worse outcome

Time frame

5 weeks, 2, 4, 6 and 10 months

Distance covered in the 6-minute walking test

Time frame

5 weeks, 2, 4, 6 and 10 months

Serum BNP concentration

Time frame

10 months

Other outcomes

Number of participants with renal failure, hyperkalemia, angioedema, and hypotension

Number of participants with hyperkalemia, renal failure (defined as a decrease in the estimated glomerular filtration rate (eGFR) of at least 50% or a decrease of at least 30ml per minute per 1.73m2 from time of enrolment to less than 60ml per minute) hypotension (systolic blood pressure \<90 mmHg), and angioedema.

Time frame

10 months

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Martin Rohacek

Lead sponsor

Swiss Tropical & Public Health Institute

Sponsor institution

Ifakara Health Institute (IHI)

Collaborator

Source ClinicalTrials.gov

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