Hypertensive Heart Failure Treatment in SSA

The Evidence-based Treatment of Hypertensive Heart Failure in Sub-Saharan Africa: A Feasibility Study

Even though, the African-American Heart Failure Trial (A- HeFT) demonstrated that a combination ISDN and HYD (BiDil) improved survival among African-American patients with HF, when compared to placebo, there is no trial on chronic heart failure patients secondary to hypertensive heart disease which is the commonest etiological factor for heart failure in sub-Saharan Africa.

A previous study (The Bi treatment with hydralazine/nitrate versus placebo in Africans admitted with acute Heart Failure (BAHEF) which was on acute heart failure patients with varying aetiology, was under powered as the study could not achieve the estimated sample size because of logistic issues.

We therefore are trying to determine the feasibility of a randomised, open-label, parallel group, two-arm, superiority trial of ISDN and hydralazine in patients with chronic hypertensive heart failure in sSA.

Study Overview

• Status: Completed
• Conditions: A Feasibility Study on Hypertensive Heart Failure Treatment
• Intervention / Treatment: Drug: Isosorbide Dinitrate

Detailed Description

Even though, the African-American Heart Failure Trial (A- HeFT) demonstrated that a combination ISDN and HYD (BiDil) improved survival among African-American patients with HF, when compared to placebo, there is no trial on chronic heart failure patients secondary to hypertensive heart disease which is the commonest etiological factor for heart failure in sub-Saharan Africa.

A previous study (The Bi treatment with hydralazine/nitrate versus placebo in Africans admitted with acute Heart Failure (BAHEF) which was on acute heart failure patients with varying aetiology, was under powered as the study could not achieve the estimated sample size because of logistic issues.

We therefore are trying to determine the feasibility of a randomised, open-label, parallel group, two-arm, superiority trial of ISDN and hydralazine in patients with chronic hypertensive heart failure in sSA. To determine the tolerability of ISDN and hydralazine in sSA.

The secondary objectives on the other hand are:

1. To determine fidelity to the trial protocol and CRF by investigators when completing a trial utilising ISDN and hydralazine in patients with chronic hypertensive heart failure in sSA.

2. To determine the effect of ISDN-HYD on the following:

   • Death and hospitalisation rates
   • Changes in office BP
   • Changes in 6MWT
   • Changes in echocardiographic left ventricular ejection fraction

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Phase 4

Contacts and Locations

Study Locations

• Nigeria
  • Federal Capital Territory
    • Abuja, Federal Capital Territory, Nigeria, 90001
      • University of Abuja Teaching Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Black male or female aged 18 years
• Evidence of hypertensive heart failure
• LVEF <40% as assessed by 2D echocardiography (modified Simpson method)
• Ability to provide written informed consent for participation in the study
• Available for regular follow-up as outlined in the schedule of assessments

Exclusion Criteria:

• Evidence of heart failure from a cause other than hypertension
• A cardiovascular/cerebrovascular event/intervention in the last three months (e.g., acute
• coronary syndrome, unstable angina, MI, PCI, CABG, stroke, carotid endarterectomy, etc.,)
• Office SBP <100 mmHg or DBP <70 mmHg
• Marked renal impairment (e.g., eGFR <45 mls/min at screening, dialysis)

• Marked hepatic impairment (e.g., history of chronic liver disease, γGT/bilirubin/ALP/ALT

  • twice the upper limit of normal)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Conventional HF medications plus ISDN & HYD; Will administer Isosorbide dinitrate (5mg bd) and Hydralazine (25mg bd) on top of conventional heart failure medications.	Drug: Isosorbide Dinitrate; Isosorbide dinitrate (5mg bd) and Hydralazine (25mg bd) will be added on top of conventional heart failure medications.
Placebo Comparator: Conventional HF medications plus placebo; We will administer placebo on top of conventional heart failure medications	Drug: Isosorbide Dinitrate; Isosorbide dinitrate (5mg bd) and Hydralazine (25mg bd) will be added on top of conventional heart failure medications.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of the study	Time taken to recruit the required subjects (n=50)	18 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Outcomes	Death and hospitalisation rates	6 months
Clinical outcomes	Changes in office BP	6 months
Clinical outcomes	Changes in 6minute walk test	6 months
Clinical outcomes	Changes in echocardiographic left ventricular ejection fraction.	6 months

Collaborators and Investigators

• Sponsor: University of Abuja
• Collaborators: University of Cambridge
• Investigators: Study Director: REGINA ASUKU, CARDIOVASCULAR RESEARCH UNIT, UNIVERSITY OF ABUJA TEACHING HOSPITAL

Publications and helpful links

General Publications

• 1. Sliwa K, et al. Readmission and death after an acute heart failure event: predictors and outcomes in sub-Saharan Africa: results from the THESUS-HF registry. Eur Heart J 2013; 34: 3151-59. 2. Cohn JN, et al. A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. N Engl J Med 2001; 345: 1667-75. 3. Lapu-Bula R, et al. From hypertension to heart failure: role of nitric oxide-mediated endothelial dysfunction and emerging insights from myocardial contrast echocardiography. Am J Cardiol 2007; 99: 7D-14D. 4. Taylor AL, et al. Combination of ISDN and hydralazine in blacks with heart failure. N Engl J Med 2004; 351: 2049-57. 5. Carson, P et al. Racial differences in response to therapy for heart failure: analysis of the vasodilator-heart failure trials. Vasodilator-Heart Failure Trial Study Group. J Card Fail 1999: 5; 178-87. 6. Damasceno A, et al. The causes, treatment, and outcome of acute heart failure in 1006 Africans from 9 countries. Arch Intern Med 2012; 172: 1386-94. 7. Sliwa K, et al. Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF). Eur J Heart Fail 2016; 18: 1248-58.

Study record dates

Study Major Dates

• Study Start (Actual): March 25, 2022
• Primary Completion (Actual): February 26, 2024
• Study Completion (Actual): March 26, 2024

Study Registration Dates

• First Submitted: December 31, 2022
• First Submitted That Met QC Criteria: May 2, 2024
• First Posted (Actual): May 6, 2024

Study Record Updates

• Last Update Posted (Actual): May 6, 2024
• Last Update Submitted That Met QC Criteria: May 2, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Natriuretic Agents; Diuretics, Osmotic; Diuretics; Nitric Oxide Donors; Isosorbide; Isosorbide Dinitrate; Isosorbide-5-mononitrate
• Other Study ID Numbers: Uniabuja; G 102642 A18971 (Other Identifier: University of Cambridge_GCFR)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No