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

NCT06704633 | Not Yet Recruiting Phase 4

• 1 other identifier: 2024-50 Heart failure Tz
• Study Type: interventional
• Target: 298
• Locations: 1 country
• Sites: 1

Brief Summary

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 238 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®.

Conditions

Heart Failure

Keywords

Sacubitril-valsartan; Heart failure with reduced ejection fraction,; HFrEF; KCCQ

Outcome Measures

Primary Outcomes (1)

• 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

  10 months

Secondary Outcomes (7)

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

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

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

  5 weeks, 2, 4, 6 and 10 months

• Distance covered in the 6-minute walking test

  5 weeks, 2, 4, 6 and 10 months

• Serum BNP concentration

  10 months

• Left ventricular ejection fraction

  6 and 10 months

Other Outcomes (1)

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

  10 months

Study Arms (1)

Symptomatic adult particiopants with HFrEF, under heart failure therapy

OTHER

Symptomatic adults with HFrEF, under heart failure medication

Drug: Sacubitril / Valsartan Oral Tablet

Interventions

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

Symptomatic adult particiopants with HFrEF, under heart failure therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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%.

You may not qualify if:

• 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
• History of angioedema
• Unacceptable side effects prior during receipt of ACE inhibitors or ARBs
• Inability to sign an informed consent form.

Sponsors & Collaborators

• Martin Rohacek: lead
• Ifakara Health Institute (IHI): collaborator

Study Sites (1)

Heart and Lung Clinic, St Francis Regional Referral Hospital, Ifakara, Tanzania

Ifakara, Morogoro, Tanzania

Location

Related Publications (11)

• Senni M, McMurray JJ, Wachter R, McIntyre HF, Reyes A, Majercak I, Andreka P, Shehova-Yankova N, Anand I, Yilmaz MB, Gogia H, Martinez-Selles M, Fischer S, Zilahi Z, Cosmi F, Gelev V, Galve E, Gomez-Doblas JJ, Nociar J, Radomska M, Sokolova B, Volterrani M, Sarkar A, Reimund B, Chen F, Charney A. Initiating sacubitril/valsartan (LCZ696) in heart failure: results of TITRATION, a double-blind, randomized comparison of two uptitration regimens. Eur J Heart Fail. 2016 Sep;18(9):1193-202. doi: 10.1002/ejhf.548. Epub 2016 May 12.

  PMID: 27170530 RESULT

• Wang TD, Tan RS, Lee HY, Ihm SH, Rhee MY, Tomlinson B, Pal P, Yang F, Hirschhorn E, Prescott MF, Hinder M, Langenickel TH. Effects of Sacubitril/Valsartan (LCZ696) on Natriuresis, Diuresis, Blood Pressures, and NT-proBNP in Salt-Sensitive Hypertension. Hypertension. 2017 Jan;69(1):32-41. doi: 10.1161/HYPERTENSIONAHA.116.08484. Epub 2016 Nov 14.

  PMID: 27849566 RESULT

• Ibrahim NE, Pina IL, Camacho A, Bapat D, Felker GM, Maisel AS, Butler J, Prescott MF, Abbas CA, Solomon SD, Januzzi JL Jr; Prospective Study of Biomarkers, Symptom Improvement and Ventricular Remodeling During Entresto Therapy for Heart Failure (PROVE-HF) Study Investigators. Racial and Ethnic Differences in Biomarkers, Health Status, and Cardiac Remodeling in Patients With Heart Failure With Reduced Ejection Fraction Treated With Sacubitril/Valsartan. Circ Heart Fail. 2020 Nov;13(11):e007829. doi: 10.1161/CIRCHEARTFAILURE.120.007829. Epub 2020 Oct 3.

  PMID: 33016100 RESULT

• Velazquez EJ, Morrow DA, DeVore AD, Duffy CI, Ambrosy AP, McCague K, Rocha R, Braunwald E; PIONEER-HF Investigators. Angiotensin-Neprilysin Inhibition in Acute Decompensated Heart Failure. N Engl J Med. 2019 Feb 7;380(6):539-548. doi: 10.1056/NEJMoa1812851. Epub 2018 Nov 11.

  PMID: 30415601 RESULT

• Thomas M, Khariton Y, Fonarow GC, Arnold SV, Hill L, Nassif ME, Chan PS, Butler J, Thomas L, DeVore AD, Hernandez AF, Albert NM, Patterson JH, Williams FB, Spertus JA. Association between sacubitril/valsartan initiation and real-world health status trajectories over 18 months in heart failure with reduced ejection fraction. ESC Heart Fail. 2021 Aug;8(4):2670-2678. doi: 10.1002/ehf2.13298. Epub 2021 May 1.

  PMID: 33932120 RESULT

• Green CP, Porter CB, Bresnahan DR, Spertus JA. Development and evaluation of the Kansas City Cardiomyopathy Questionnaire: a new health status measure for heart failure. J Am Coll Cardiol. 2000 Apr;35(5):1245-55. doi: 10.1016/s0735-1097(00)00531-3.

  PMID: 10758967 RESULT

• McMurray JJ, Packer M, Desai AS, Gong J, Lefkowitz MP, Rizkala AR, Rouleau JL, Shi VC, Solomon SD, Swedberg K, Zile MR; PARADIGM-HF Investigators and Committees. Angiotensin-neprilysin inhibition versus enalapril in heart failure. N Engl J Med. 2014 Sep 11;371(11):993-1004. doi: 10.1056/NEJMoa1409077. Epub 2014 Aug 30.

  PMID: 25176015 RESULT

• Mebazaa A, Davison B, Chioncel O, Cohen-Solal A, Diaz R, Filippatos G, Metra M, Ponikowski P, Sliwa K, Voors AA, Edwards C, Novosadova M, Takagi K, Damasceno A, Saidu H, Gayat E, Pang PS, Celutkiene J, Cotter G. Safety, tolerability and efficacy of up-titration of guideline-directed medical therapies for acute heart failure (STRONG-HF): a multinational, open-label, randomised, trial. Lancet. 2022 Dec 3;400(10367):1938-1952. doi: 10.1016/S0140-6736(22)02076-1. Epub 2022 Nov 7.

  PMID: 36356631 RESULT

• Raphael DM, Roos L, Myovela V, Mchomvu E, Namamba J, Kilindimo S, Gingo W, Hatz C, Paris DH, Weisser M, Kobza R, Rohacek M. Heart diseases and echocardiography in rural Tanzania: Occurrence, characteristics, and etiologies of underappreciated cardiac pathologies. PLoS One. 2018 Dec 26;13(12):e0208931. doi: 10.1371/journal.pone.0208931. eCollection 2018.

  PMID: 30586432 RESULT

• Dokainish H, Teo K, Zhu J, Roy A, AlHabib KF, ElSayed A, Palileo-Villaneuva L, Lopez-Jaramillo P, Karaye K, Yusoff K, Orlandini A, Sliwa K, Mondo C, Lanas F, Prabhakaran D, Badr A, Elmaghawry M, Damasceno A, Tibazarwa K, Belley-Cote E, Balasubramanian K, Islam S, Yacoub MH, Huffman MD, Harkness K, Grinvalds A, McKelvie R, Bangdiwala SI, Yusuf S; INTER-CHF Investigators. Global mortality variations in patients with heart failure: results from the International Congestive Heart Failure (INTER-CHF) prospective cohort study. Lancet Glob Health. 2017 Jul;5(7):e665-e672. doi: 10.1016/S2214-109X(17)30196-1. Epub 2017 May 3. Erratum In: Lancet Glob Health. 2017 Jul;5(7):e664. doi: 10.1016/S2214-109X(17)30199-7.

  PMID: 28476564 RESULT

• Chillo P, Mlay J, Akanyirige PW, Majani N, Janabi M, Kaaya S, Hawkins C, Hirschhorn LR. Adapting and usability testing of the Kansas city cardiomyopathy questionnaire (KCCQ) in a heart failure clinic in Tanzania: the Swahili KCCQ. BMC Cardiovasc Disord. 2023 May 6;23(1):242. doi: 10.1186/s12872-023-03265-0.

  PMID: 37149565 RESULT

MeSH Terms

Conditions

Heart Failure

Interventions

sacubitril and valsartan sodium hydrate drug combination

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Study Officials

• Samuel S Mutasingwa, MD

  Ifakara Health Iistitute

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Martin Rohacek, PD Dr med

CONTACT

+255625064252; mrohacek@ihi.or.tz

Samuel S Mutasingwa, MD

CONTACT

+255757383124; ssalvatory@ihi.or.tz

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Project Leader

Model Details: This is an interventional single center single group open label pre-post study with a follow-up of 10 months.

Study Record Dates

• First Submitted: November 21, 2024
• First Posted: November 26, 2024
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): October 30, 2028
• Study Completion (Estimated): October 30, 2028
• Last Updated: April 24, 2026

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• Time Frame: 12-2027
• Access Criteria: IPD will be shared upon justified request

Locations

TA (1)