NCT01822808

Brief Summary

To investigate the effect of hydralazine isosorbide dinitrate on clinical outcomes, symptoms, cardiac parameters and functional status of African patients hospitalized with AHF and left ventricular dysfunction during 24 weeks of therapy. Administration of hydralazine/nitrates will be superior to placebo administration in reducing HF readmission or death, improving dyspnoea, reducing blood pressure and brain natriuretic peptide (BNP) in African patients admitted with AHF and left ventricular dysfunction.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
500

participants targeted

Target at P50-P75 for phase_3

Timeline
Completed

Started Jan 2013

Typical duration for phase_3

Geographic Reach
1 country

1 active site

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 2013

Completed
3 months until next milestone

First Submitted

Initial submission to the registry

March 25, 2013

Completed
8 days until next milestone

First Posted

Study publicly available on registry

April 2, 2013

Completed
2.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2016

Completed
6 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2016

Completed
Last Updated

August 14, 2015

Status Verified

August 1, 2015

Enrollment Period

3 years

First QC Date

March 25, 2013

Last Update Submit

August 13, 2015

Conditions

Acute Heart FailureLeft Ventricular Dysfunction

Keywords

acute heart failureleft ventricular dysfunctionhydralazineisosorbide dinitrate

Outcome Measures

Primary Outcomes (1)

  • Time to death or HF re-admission

    In African patients admitted with acute heart failure, to investigate the effect of the combination of hydralazine/isosorbide dinitrate (HYIS) on the rate of death or re-admission for HF during 24 weeks of therapy

    through to day 180

Secondary Outcomes (5)

  • Change in symptoms of heart failure

    within 7 days post randomization

  • Change in systolic blood pressure

    within 7 days post randomization

  • Functional status

    7 days post randomization

  • Changes in serum creatinine

    up to 8 weeks post randomization

  • Change in left ventricular dimensions

    up to 24 weeks post randomization

Study Arms (2)

Hydralazine

ACTIVE COMPARATOR

24 week course of Hydralazine 25mg 3 times daily for 4 weeks, thereafter uptitrating to 50mg hydralazine 3 times daily up to week 24. Those assigned to the Hydralazine control arm will receive the same number of identical placebo tablets.

Drug: Hydralazine

Isosorbide dinitrate

ACTIVE COMPARATOR

24 week course of Isosorbide dinitrate 10mg 3 times daily for 4 weeks, thereafter uptitrating to 20mg isosorbide dinitrate 3 times daily up to week 24. Those assigned to the Isosorbide dinitrate control arm will receive the same number of identical placebo tablets.

Drug: Isosorbide Dinitrate

Interventions

HydralazineDRUG

Hydralazine and placebo will be supplied as 25mg identical tablets and given at a dosage of 75mg/day up to week 4, thereafter 150mg/day up to week 24.

Also known as: Hyperphen
Hydralazine
Isosorbide DinitrateDRUG

Isosorbide dinitrate and placebo will be supplied as 10mg identical tablets and given at a dosage of 30mg/day up to week 4, thereafter 60mg/day up to week 24.

Also known as: Isordil
Isosorbide dinitrate

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • \> 18 years of age
  • Hospital admission for acute heart failure as defined by the presence of acute dyspnea and the presence of clinical signs of heart failure on physical examination.
  • Where available, NT-proBNP \>900 pg/ml, \>1800 pg/ml if the patient has atrial fibrillation at screening or \>450 pg/ml if BMI \> 35 kg/m2, LVEF \<45% assessed by echocardiography or other method within the previous 12 months
  • Background therapy with at least ACE-inhibitor or angiotensin receptor blocker (ARB) and beta-blocker (unless beta-blocker is contraindicated due to severe volume overload, low output heart failure, or cardiogenic shock)
  • Available for regular follow up

You may not qualify if:

  • Currently being treated with Hydralazine and/or nitrates or a history of intolerance to oral therapy with either hydralazine or nitrates.
  • Any intravenous treatment for heart failure, except IV furosemide (eg. IV inotropes, pressors, nitrates or nesiritide) at the time of screening.
  • Systolic blood pressure \<100 mmHg
  • Plan for revascularization
  • Greater than 96 hours after admission
  • Reversible etiology of acute heart failure such as myocarditis, acute myocardial infarction, arrhythmia. Acute MI is defined as symptoms and major electrocardiogram (ECG) changes(i.e., ST segment elevations), and arrhythmia includes unstable heart rates above 120/min or below 50/min.
  • Hypertrophic obstructive cardiomyopathy, constrictive cardiomyopathy, endomyocardial fibroelastosis
  • Known severe congenital heart disease (such as uncorrected tetralogy of fallot or transposition of the aorta)
  • Severe aortic or mitral stenosis or severe rheumatic mitral regurgitation.
  • Renal impairment (defined by creatinine \>3 mg/dL) at screening or on any type of dialysis.
  • Known hepatic impairment (total bilirubin \>3mg/dl) or increased ammonia levels at screening.
  • History of systemic lupus erythematous.
  • Stroke or TIA within 2 weeks from screening.
  • Women who are pregnant or lactating.
  • Allergy to organic nitrates.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Hatter Institute for Cardiovascular Research in Africa

Cape Town, Western Cape, 7925, South Africa

Location

Related Publications (2)

  • Sani MU, Damasceno A, Davison BA, Cotter G, Mayosi BM, Edwards C, Azibani F, Adam T, Arif G, Jessen N, Sliwa K. N-terminal pro BNP and galectin-3 are prognostic biomarkers of acute heart failure in sub-Saharan Africa: lessons from the BAHEF trial. ESC Heart Fail. 2021 Feb;8(1):74-84. doi: 10.1002/ehf2.13032. Epub 2020 Nov 28.

    PMID: 33247624DERIVED

  • Sliwa K, Damasceno A, Davison BA, Mayosi BM, Sani MU, Ogah O, Mondo C, Ojji D, Dzudie A, Kouam CK, Yonga G, Ba SA, Ogola E, Edwards C, Milo O, Cotter G. Bi treatment with hydralazine/nitrates vs. placebo in Africans admitted with acute HEart Failure (BA-HEF). Eur J Heart Fail. 2016 Oct;18(10):1248-1258. doi: 10.1002/ejhf.581. Epub 2016 May 20.

    PMID: 27206810DERIVED

MeSH Terms

Conditions

Ventricular Dysfunction, Left

Interventions

HydralazineIsosorbide Dinitrate

Condition Hierarchy (Ancestors)

Ventricular DysfunctionHeart DiseasesCardiovascular Diseases

Intervention Hierarchy (Ancestors)

PhthalazinesPyridazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsIsosorbideSorbitolSugar AlcoholsAlcoholsOrganic ChemicalsCarbohydrates

Study Officials

  • Karen Sliwa, PhD

    Hatter Institute for Cardiovascular Research In Africa (HICRA), University of Cape Town

    PRINCIPAL INVESTIGATOR

  • Gad Cotter, MD

    Momentum Research, Inc.

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor

Study Record Dates

First Submitted

March 25, 2013

First Posted

April 2, 2013

Study Start

January 1, 2013

Primary Completion

January 1, 2016

Study Completion

July 1, 2016

Last Updated

August 14, 2015

Record last verified: 2015-08

Locations

ZA(1)