Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12607000269437
Ethics application status
Not yet submitted
Date submitted
16/05/2007
Date registered
18/05/2007
Date last updated
18/05/2007
Type of registration
Prospectively registered

Titles & IDs
Public title
Nitrates and Hydralazine in Heart Failure
Scientific title
Combination of Organic Nitrates and Hydralazine in the Management of Symptoms in Patients With Systolic Heart Failure Receiving Contemporary Neurohormonal Inhibition.
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Failure 1809 0
Condition category
Condition code
Cardiovascular 1899 1899 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Randomised, Double Blind, Placebo Controlled, Crossover Design, Single Center Pilot Study.
Target Population: symptomatic adult patients with evidence of significant systolic left ventricle dysfunction (with Left Ventricle Ejection Fraction<40%) on maximal medical treatment.
Intervention: use of organic nitrates(isosorbide dinitrate) and hydralazine with placebo (tablets) as a comparator
Dose 40mg three times daily (Isosorbide) and 50mg three times daily (Hydralazine) for total of 12 months with 1 month washout. Crossover will be performed at 6 months (each arm will receive 6 months of study medications and 6 months of placebo )
Total number of visits 13.
Informed consent will be obtained in the eligible subjects at the initial Visit 1.
Visit 2, 3 and 4 will be scheduled in two weekly intervals.
Subsequent visits will be at 2 monthly intervals (Visits 5, 6 and 7).
A wash-out period will follow and will last 4 weeks. Subsequently crossover between treatment arms will be performed at Visit 8. Visit 9 and 10 follow every 2 weeks.
Visits 11,12 and 13 planned at 2 monthly intervals.
Intervention code [1] 1760 0
Treatment: Drugs
Comparator / control treatment
Placebo
Control group
Placebo

Outcomes
Primary outcome [1] 2698 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
1. The change in exercise time to identify an 18% improvement of VO2 max (maximal Oxygen consumption)
Timepoint [1] 2698 0
Determined by an incremental exercise test at Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Primary outcome [2] 2699 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
2. Change in exercise tolerance as measured by the 6 Minute Walk Test
Timepoint [2] 2699 0
At Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Primary outcome [3] 2700 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
3. Quality of life parameters as measured by the Minnesota Living with Heart Failure Questionnaire
Timepoint [3] 2700 0
At Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Primary outcome [4] 2701 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
4. Left ventricular volume
Timepoint [4] 2701 0
At either Visit 7 or Visit 13 compared with baseline dependent on randomisation stratification.
Primary outcome [5] 2702 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
5. Left Ventricle ejection fraction at either visit 7 or visit 13
Timepoint [5] 2702 0
At Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Primary outcome [6] 2703 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
6. The degree of Mitral Regurgitation at either visit 7 or visit 13
Timepoint [6] 2703 0
At Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Primary outcome [7] 2704 0
The primary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
7. Diastolic indices at visit 7 or visit 13
Timepoint [7] 2704 0
At Visits 7 or 13 compared with baseline dependent on randomisation stratification.
Secondary outcome [1] 4563 0
Secondary Endpoint:
The secondary endpoint of this study is the comparison of hydralazine and nitrate therapy and placebo on:
1. Time to first hospitalisation admission with worsening heart failure
Timepoint [1] 4563 0
At either Visit 7 or Visit 13 at Visits 7 or 13 compared with baseline dependent on randomisation stratification.

Eligibility
Key inclusion criteria
2.Chronic heart failure class II, III or IV New York Heart Association for > 3 months3. Left Ventricle Ejection Fraction <=40% (within 3 months of entry to the study)4. Stable medical therapy >3 months (including Beta Blocker, Angiotensin Converting Enzyme Inhibitor or Angiotensin Receptor Blocker and Spironolactone or Eplerenone if applicable. This inclusion criteria excludes Frusemide because Frusemide dosage may vary daily depending on medical advice.)5. Women of childbearing potential must be willing to use effective contraceptives to prevent pregnancy during the course of the study.6. Women of child-bearing potential must have a negative pregnancy before randomisation.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Cardiogenic shock 2. Unstable coronary syndrome within 3/123. Recent myocardial infarction (3/12)4. Severe aortic stenosis5. Severe symptomatic coronary artery disease6. Restrictive cardiomyopathy, constrictive pericarditis7. Hypotension (mean Blood Pressure <80mmHg)8. Significant renal impairment with creatinine >200 mcmol/l 9. Unable to provide consent, comply with follow-up visits and/or respond to the questionnaire10. Currently involved in or has been involved in another clinical trial using an investigational drug or device in the previous 30 days.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Patients meeting the inclusion criteria will be identified and approached at the time of admission to hospital or during regular visit to the outpatient clinics (cardiology and heart failure). Subjects will be excluded if met any of the exclusion criteria listed above is present. Informed consent will be obtained in the eligible subjects at the initial Visit 1. The study drugs or placebo will be randomly allocated by contacting the pharmacy with kit number which will be assigned to prepacked set of study medications/placebo by random.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation by using a randomisation table from a statistic book
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Blinded are the study participants, the people administering the treatment/s (pharmacist, research nurses, clinicians)and the people assessing the outcomes (assessors)
Phase
Phase 4
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
15/07/2007
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
160
Accrual to date
Final

Funding & Sponsors
Funding source category [1] 2045 0
Hospital
Name [1] 2045 0
Princess Alexandra Hospital Society
Country [1] 2045 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Alphapharm
Address
Country
Australia
Secondary sponsor category [1] 1851 0
Hospital
Name [1] 1851 0
Heart Failure Unit, Division of Medicine, Princess Alexandra Hospital, Brisbane
Address [1] 1851 0
Country [1] 1851 0
Australia

Ethics approval
Ethics application status
Not yet submitted
Ethics committee name [1] 3781 0
Princess Alexandra Hospital Human Research Ethics Committee
Ethics committee address [1] 3781 0
Ethics committee country [1] 3781 0
Australia
Date submitted for ethics approval [1] 3781 0
Approval date [1] 3781 0
Ethics approval number [1] 3781 0

Summary
Brief summary
Nitrates and Hydralazine are well known drugs being used in management of angina and hypertension. They have been tried in patients with heart failure who can not use Angiotensin Converting Enzyme (ACE) inhibitors and in African American population of USA on the top of ACE inhibitors, but have not been tested in addition to ACE inhibitors in Australian population.
The purpose of this research study is to evaluate the benefit of optimising medical treatment in symptomatic patients with heart failure by addition of Nitrate and Hydralazine. This will hopefully translate into decrease of the symptoms of heart failure, increase in subjects exercise capacity and improvement of their quality of life.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 27863 0
Address 27863 0
Country 27863 0
Phone 27863 0
Fax 27863 0
Email 27863 0
Contact person for public queries
Name 10949 0
Cindy Hall
Address 10949 0
Princess Alexandra Hospital
Ipswich Road
Woolloongabba QLD 4201
Country 10949 0
Australia
Phone 10949 0
+61 7 32405145
Fax 10949 0
Email 10949 0
cindy_hall@health.qld.gov.au
Contact person for scientific queries
Name 1877 0
Dariusz Korczyk
Address 1877 0
Princess Alexandra Hospital
Ipswich Road
Woolloongabba QLD 4201
Country 1877 0
Australia
Phone 1877 0
+61 7 32405442
Fax 1877 0
Email 1877 0
dariusz_korczyk@health.qld.gov.au

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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