A randomised controlled trial of the effect of angiotensin-converting enzyme inhibitors on pulmonary regurgitation, biventricular volume, mass and function, integrated cardiopulmonary exercise and cardiac autonomic reflexes late after Tetralogy of Fallot repair. The APPROPRIATE study (Ace inhibitors for PRevention Of Pulmonary Regurgitation In Adults with TEtralogy)

ISRCTN	ISRCTN97515585
DOI	https://doi.org/10.1186/ISRCTN97515585
Protocol serial number	BHF Project Grant PG/02/027
Sponsor	British Heart Foundation (UK)
Funders	British Heart Foundation, Project Grant PG/02/027

Submission date: 06/07/2005
Registration date: 08/08/2005
Last edited: 05/11/2010

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Michael A. Gatzoulis
Scientific

Adult Congenital Heart Unit
Royal Brompton Hospital
Sydney Street
London
SW3 6NP
United Kingdom

Phone	+44 (0)20 7351 8602
Email	m.gatzoulis@rbh.nthames.nhs.uk

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	APPROPRIATE
Study objectives	Angiotensin-Converting Enzyme (ACE) inhibitor therapy reduces the degree of pulmonary regurgitation and improves right ventricular function, exercise capacity and baroreceptor sensitivity in patients with repaired Tetralogy of Fallot and pulmonary regurgitation.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Repaired Tetralogy of Fallot
Intervention	Ramipril 10 mg once daily for six months compared to placebo (blister packaged capsules indistinguishable from the blister packaged active drug and also taken in increasing dose 2.5 mg for one week, then 5 mg for two weeks then 10 mg for rest of study). All patients have two safety blood tests on the basis that they may be on ramipril. There is a protocol of openly changing to losartan in the circumstance of intractable cough. The trial is double blinded and all investigators remain blind as the study is ongoing.
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Ramipril
Primary outcome measure(s)	Improvement in right ventricular function
Key secondary outcome measure(s)	1. Reduction in pulmonary regurgitant fraction 2. Reduction of right ventricular volume 3. Reduction of right ventricular mass 4. Reduction of left ventricular volume 5. Improvement of left ventricular systolic function 6. Improvement of exercise performance 7. Improvement in baroreceptor sensitivity and heart rate variability
Completion date	14/07/2005

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	60
Key inclusion criteria	All patients with repaired Tetralogy of Fallot and moderate or more pulmonary regurgitant fraction.
Key exclusion criteria	1. Known allergy or hypersensitivity to ACE-inhibitors 2. History of coronary artery disease 3. Pulmonary stenosis more than mild 4. Unable to undertake Cardiovascular Magnetic Resonance (permanent pacemaker, electrical device etc.) 5. Renal failure, assessed from patients clinical notes and baseline biochemistry check. 6. Ongoing ACE-inhibitor therapy 7. Pregnancy/breastfeeding/planning to conceive during participation 8. Systolic blood pressure less than 90 mmHg 9. Hyperkaliemia (K+ levels more than 5.5 mEq/l) 10. Refusal to give informed consent
Date of first enrolment	01/10/2002
Date of final enrolment	14/07/2005

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Adult Congenital Heart Unit

London
SW3 6NP
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	09/02/2012		Yes	No