Bi Treatment With Hydralazine/Nitrates Versus Placebo in Africans Admitted With Acute Heart Failure (B-AHEF)

This study is currently recruiting participants.
Verified March 2013 by University of Cape Town
Sponsor:
Collaborator:
Momentum Research, Inc.
Information provided by (Responsible Party):
Prof. Karen Sliwa-Hahnle, University of Cape Town
ClinicalTrials.gov Identifier:
NCT01822808
First received: March 25, 2013
Last updated: April 1, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Acute Heart Failure
Left Ventricular Dysfunction
Drug: Hydralazine
Drug: Isosorbide Dinitrate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Prospective, Placebo-controlled, Double-blind, Randomized Study to Compare Treatment With Hydralazine-isosorbide-dinitrate (HYIS) Versus Placebo on Top of Standard Care in African Patients Admitted With Acute Heart Failure (AHF) and Left Ventricular Dysfunction

Resource links provided by NLM:


Further study details as provided by University of Cape Town:

Primary Outcome Measures:
  • Time to death or HF re-admission [ Time Frame: through to day 180 ] [ Designated as safety issue: Yes ]
    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


Secondary Outcome Measures:
  • Change in symptoms of heart failure [ Time Frame: within 7 days post randomization ] [ Designated as safety issue: Yes ]
    Change in symptoms of HF from baseline to 7 days post randomization or discharge, as assessed by dyspnoea severity and global well being on a VAS scale

  • Change in systolic blood pressure [ Time Frame: within 7 days post randomization ] [ Designated as safety issue: Yes ]
    Change in systolic blood pressure from baseline to 7 days post randomization or discharge and at 8 weeks and 24 weeks post randomization

  • Functional status [ Time Frame: 7 days post randomization ] [ Designated as safety issue: No ]
    Functional status assessed by 6 minute walk at 7 days post randomization or discharge, and at 8 weeks and 24 weeks post randomization

  • Changes in serum creatinine [ Time Frame: up to 8 weeks post randomization ] [ Designated as safety issue: No ]
    Changes in serum creatinine, blood urea nitrogen (BUN) and estimated glomerular filtration rate (eGFR) from baseline to 8 weeks post randomization and at 24 weeks post randomization

  • Change in left ventricular dimensions [ Time Frame: up to 24 weeks post randomization ] [ Designated as safety issue: Yes ]
    Change in left ventricular dimensions and left ventricular ejection fraction (LVEF) from baseline to 24 weeks post randomization.


Estimated Enrollment: 500
Study Start Date: January 2013
Estimated Study Completion Date: July 2016
Estimated Primary Completion Date: January 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Hydralazine
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
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.
Other Name: Hyperphen
Active Comparator: Isosorbide dinitrate
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
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.
Other Name: Isordil

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. > 18 years of age
  2. Hospital admission for acute heart failure as defined by the presence of acute dyspnea and the presence of heart failure signs by physical examination with at least 2 of the following: rales, oedema, elevated JVP, hepatomegaly, ascites
  3. 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
  4. 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)
  5. Available for regular follow up

Exclusion Criteria:

  1. Any intravenous treatment for heart failure, except IV furosemide (eg. IV inotropes, pressors, nitrates or nesiritide) at the time of screening.
  2. Systolic blood pressure <100 mmHg
  3. Plan for revascularization
  4. Greater than 48 hours after admission
  5. Reversible etiology of acute heart failure such as myocarditis, acute myocardial infarction, arrhythmia
  6. Hypertrophic obstructive cardiomyopathy, restrictive or constrictive cardiomyopathy, endomyocardial fibroelastosis
  7. Known severe congenital heart disease (such as uncorrected tetralogy of fallot or transposition of the aorta)
  8. Significant stenotic valvular disease
  9. Renal impairment (defined by creatinine >3 mg/dL) at screening or on any type of dialysis.
  10. Known hepatic impairment (total bilirubin >3mg/dl) or increased ammonia levels at screening.
  11. Acute coronary syndromes within 2 weeks from screening.
  12. Non-cardiac pulmonary oedema.
  13. Known sensitivity or intolerance to angiotensin converting enzyme (ACE) inhibitors.
  14. History of systemic lupus erythematosus.
  15. SEVERE Mitral valve rheumatic heart disease.
  16. Severe cerebrovascular disease, including acute stroke or cerebral ischaemia.
  17. Women who are pregnant or lactating.
  18. Allergy to organic nitrates.
  19. History or presence of any other diseases (ie. Including malignancies or AIDS) with a life expectancy of < 12 months
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01822808

Contacts
Contact: Karen Sliwa, PhD +27-21-4066358 karen.sliwa-hahnle@uct.ac.za
Contact: Lavinia Petersen 27722171166 lavinia.petersen@uct.ac.za

Locations
South Africa
Hatter Institute for Cardiovascular Research in Africa Recruiting
Cape Town, Western Cape, South Africa, 7925
Contact: Karen Sliwa, PhD    +27-21-4066358    karen.sliwa-hahnle@uct.ac.za   
Contact: Lavinia Petersen    +27-72-2171166    lavinia.petersen@uct.ac.za   
Principal Investigator: Karen Sliwa, PhD         
Sub-Investigator: Bongani Mayosi, MD PhD         
Sub-Investigator: Mpiko Ntsekhe, MD         
Sub-Investigator: Dirk Blom, MD         
Sub-Investigator: Tawanda Butau, MD         
Sub-Investigator: Kemi Tibazarwa, MD         
Sponsors and Collaborators
University of Cape Town
Momentum Research, Inc.
Investigators
Principal Investigator: Karen Sliwa, PhD Hatter Institute for Cardiovascular Research In Africa (HICRA), University of Cape Town
Study Director: Gad Cotter, MD Momentum Research, Inc.
  More Information

No publications provided

Responsible Party: Prof. Karen Sliwa-Hahnle, Professor, University of Cape Town
ClinicalTrials.gov Identifier: NCT01822808     History of Changes
Other Study ID Numbers: B-AHEF
Study First Received: March 25, 2013
Last Updated: April 1, 2013
Health Authority: South Africa: Medicines Control Council

Keywords provided by University of Cape Town:
acute heart failure
left ventricular dysfunction
hydralazine
isosorbide dinitrate

Additional relevant MeSH terms:
Heart Failure
Ventricular Dysfunction, Left
Ventricular Dysfunction
Heart Diseases
Cardiovascular Diseases
Hydralazine
Isosorbide-5-mononitrate
Isosorbide Dinitrate
Isosorbide
Antihypertensive Agents
Cardiovascular Agents
Therapeutic Uses
Pharmacologic Actions
Vasodilator Agents
Diuretics, Osmotic
Diuretics
Natriuretic Agents
Physiological Effects of Drugs
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on April 20, 2014