ANZCTR - Registration

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Trial registered on ANZCTR

Registration number

ACTRN12612000684820

Ethics application status

Approved

Date submitted

22/06/2012

Date registered

26/06/2012

Date last updated

3/07/2012

Type of registration

Prospectively registered

Titles & IDs

Public title

Novel Interventions in Heart Failure with Preserved Ejection Fraction using Tadalafil

Scientific title

Novel Interventions in Heart Failure with Preserved Ejection Fraction -a single centre, randomised double blind placebo cross-over pilot study using Tadalafil, to assess the effect on 6 minute walk test, peak oxygen consumption and New York Heart Association class of symptoms, from the Flinders Clinical Research , Flinders University.

Secondary ID [1]

Nil

Universal Trial Number (UTN)

U1111-1132-0591

Trial acronym

NIHEF-2012T
(Novel Interventions in Heart Failure with Preserved Ejection Fraction using Tadalafil) 20- refers to the number of patients in the trial, 2012- refers to the year of study, T refers to first letter in Tadalafil

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Heart Failure with Preserved Ejection Fraction

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

Effect of Tadalafil in Heart failure with preserved ejection fraction
Dose of Tadalafil-40mg once daily, oral capsules
For 8 weeks and then, there is a 2 week wash out period and they will be crossed over to placebo for 8 weeks

Intervention code [1]

Treatment: Drugs

Comparator / control treatment

Placebo-microcellulose oral capsule

Control group

Placebo

Outcomes

Primary outcome [1]

Improvement in 6 minute walk test

Timepoint [1]

Baseline, 8 and 18 weeks after randomistaion

Primary outcome [2]

Peak oxygen consumption based on Cardiopulmonary exercise testing. The VO2 is calculated from the heart rate difference between rest and peak exercise.
During the cardiopulmonary exercise test, Heart rate, Blood pressure and the inspired oxygen levels are continously measured by ECG and other monitors.

Timepoint [2]

Baseline, 8 and 18 weeks after randomistaion

Primary outcome [3]

New York Heart Association Class, as assessed by interview

Timepoint [3]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [1]

RV volume as assessed on cardiac magnetic resonance imaging

Timepoint [1]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [2]

RVEF as assessed on cardiac magnetic resonance imaging

Timepoint [2]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [3]

LV diastolic parameters (E/A, E/E') as assessed on Echocardiogram

Timepoint [3]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [4]

Pulmonary artery pressure as assessed on Echocardiogram

Timepoint [4]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [5]

Cardiac output as assessed on cardiac magnetic resonance imaging

Timepoint [5]

Baseline, 8 and 18 weeks after randomistaion

Secondary outcome [6]

BNP levels on blood test sample

Timepoint [6]

Baseline, 8 and 18 weeks after randomistaion

Eligibility

Key inclusion criteria

Age greater than or equal to 18 years
HF-PEF (LVEF greater than or equal to 50% within 6m of randomisation)
NYHA II-III
Diastolic dysfunction on echo
E/A equal to 1, E/E’ equal to 15, deceleration time less than or equal to 140ms
Systolic pulmonary artery pressure over 30 mm of Hg
Stable disease, confirmed by no hospital admissions or HF medication changes within 3m prior to randomisation
Informed consent
No other causes for exertional dyspnoea

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

No

Key exclusion criteria

Contraindications to Tadalafil ; Nitrate use in any form
Contraindications to MRI
Significant valvular or coronary disease as primary cause of HF
Hypertrophic cardiomyopathy, cardiac amyloidosis, sarcoidosis
GFR greater than or equal to 45 ml/min

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)

20 patients recruited for the study will be randomised to receive Tadalafil or placebo once daily for 8 weeks in addition to their usual medications. They will then be crossed over to the other treatment for 8 weeks after a 2 week wash-out period.
Allocation is done by numbered containers by the company that does the randomisation for us.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)

Randomisation to study drug or placebo is based on a block randomisation. Blocking is used to ensure that comparison groups will be generated according to a predetermined ratio, usually 1:1 or groups of approximately the same size.

Masking / blinding

Blinded (masking used)

Who is / are masked / blinded?

Intervention assignment

Crossover

Other design features

Phase

Phase 4

Type of endpoint/s

Efficacy

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

24/07/2012

Actual

Date of last participant enrolment

Anticipated

Actual

Date of last data collection

Anticipated

Actual

Sample size

Target

20

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

Funding & Sponsors

Funding source category [1]

Self funded/Unfunded

Name [1]

Address [1]

Country [1]

Primary sponsor type

Other Collaborative groups

Name

South Australian Health and Medical Reseasrch Institute

Address

Box 15,Level 1b,
Mark Oliphant Building
Laffer Drive,Science Park
Bedford Park, SA 5042

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Southern Adelaide Clinical Human Research Ethics Committee

Ethics committee address [1]

Flinders Medical Centre,The Flats G5, Room 3 and 4,Flinders Drive, Bedford Park, SA-5042, Australia

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

Approval date [1]

13/06/2012

Ethics approval number [1]

207.12b

Summary

Brief summary

It is estimated that over 300,000 Australians have heart failure (HF) at any given time and the incidence increases with increase in life expectancy. The point prevalence of chronic heart failure (CHF) has been about 1% in people aged 50–59 years, 10% in people aged over 65 years, and over 50% in people aged greater than 85 years. Despite therapeutic advances, HF remains a disease with unacceptably high mortality rates, poor quality of life and massive socioeconomic cost. Heart failure with preserved ejection fraction (HF-PEF) previously known as diastolic heart failure accounts for about 50% of patients with heart failure. HF-PEF refers to a clinical syndrome of symptoms and clinical signs of HF, normal or near normal left ventricular (LV) systolic function (EF> 50%) and evidence of diastolic dysfunction in the form of abnormal LV filling and elevated filling pressures. This can be objectively confirmed on echocardiogram.
There is no difference in morbidity between patients with heart failure with reduced ejection fraction and those with preserved ejection fraction and some studies have shown similar mortality in the two conditions. The efficacy for beta blockers, angiotensin converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB) and aldosterone antagonists is well established in the treatment of HF with reduced EF. The efficacy for these drugs in HF-PEF is not well established. The I-PRESERVE trial studied the effects of Irbesartan (ARB) in symptomatic patients with HF-PEF. 4128 patients were enrolled and followed up for 4 years. There was no improvement in outcomes in patients on Irbesartan. The CHARM preserved trial studied Candesartan in 3000 patients with HF-PEF for a period of 3 years. There was only a small reduction in hospital admissions for heart failure in the Candesartan group.The PEP-CHF trial assessed the efficacy of Perindopril (ACE-I) in 850 patients over the age of 70 with HF-PEF. At one year there were fewer unexpected hospital admissions for heart failure in the perindopril group although the trial when completed showed no difference in its primary end point.  Although therapies have proven effective in reducing morbidity and mortality from heart failure with reduced ejection fraction, mortality from HF-PEF remains unchanged. No therapies thus far have been proven to correct the abnormalities seen in HF-PEF, halt its progression, reduce its mortality or conclusively reduce its morbidity.
Rationale.
1. That the addition of the phosphodiestrase-5 (PDE-5) inhibitor tadalafil will improve symptoms, exercise tolerance, pulmonary arterial pressure, right ventricular (RV) function and  LV relaxation in patients with HF- PEF.
Objectives.
The primary objective of the study is to trial a novel agent in the treatment of HF-PEF as patients continue to be symptomatic on currently available medications.
1. We propose to use the PDE-5 inhibitor tadalafil which selectively dilates pulmonary vessels and has beneficial effects on RV function in patients with HF-PEF and assess the effect on symptoms, exercise tolerance, echocardiographic and Cardiovascular Magnetic Resonance (CMR) imaging parameters of heart failure.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Address

Country

Phone

Fax

Email

Contact person for public queries

Name

Dr. Govindarajan Srinivasan

Address

Department of Cardiovascular Medicine
Flinders Medical Centre,1 Flinders Drive
Bedford Park, SA, 5042

Country

Australia

Phone

+61-08-8201 7700

Fax

+61-08-82017701

Email

Govindarajan.Srinivasan@health.sa.gov.au

Contact person for scientific queries

Name

Dr. Govindarajan Srinivasan

Address

Department of Cardiovascular Medicine
Flinders Medical Centre,1 Flinders Drive
Bedford Park, SA, 5042

Country

Australia

Phone

+61-08-8201 7700

Fax

+61-08-82017701

Email

Govindarajan.Srinivasan@health.sa.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

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.