Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System (Redefine)
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ClinicalTrials.gov Identifier: NCT02010905 |
Recruitment Status : Unknown
Verified December 2015 by Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA).
Recruitment status was: Recruiting
First Posted : December 13, 2013
Last Update Posted : December 22, 2015
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Tracking Information | |||
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First Submitted Date ICMJE | December 6, 2013 | ||
First Posted Date ICMJE | December 13, 2013 | ||
Last Update Posted Date | December 22, 2015 | ||
Study Start Date ICMJE | December 2013 | ||
Estimated Primary Completion Date | January 2018 (Final data collection date for primary outcome measure) | ||
Current Primary Outcome Measures ICMJE |
Right ventricular ejection fraction [ Time Frame: two years ] RV EF is measured by means of cardiovascular magnetic resonance imaging (CMR)
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Original Primary Outcome Measures ICMJE | Same as current | ||
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Current Secondary Outcome Measures ICMJE |
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Original Secondary Outcome Measures ICMJE |
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Current Other Pre-specified Outcome Measures | Not Provided | ||
Original Other Pre-specified Outcome Measures | Not Provided | ||
Descriptive Information | |||
Brief Title ICMJE | Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System | ||
Official Title ICMJE | Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-angiotensin-aldosterone System | ||
Brief Summary | Rationale: The prevalence of adult patients with congenital heart disease (CHD) has steadily increased over the last decades, due to the advances in cardiac surgery. A large number of these patients cope with right ventricular (RV) volume or pressure overload, largely caused by residual lesions after cardiac surgery in childhood. Previous RV overload due to pulmonary regurgitation in Tetralogy of Fallot (TOF) can lead to RV dysfunction. These findings warrant close surveillance of RV function, and adequate and evidence-based pharmacological therapy to reduce both morbidity and mortality in this young patient group. The renin-angiotensin-aldosterone system (RAAS) is activated in patients with ventricular failure, irrespective of the effected (left or right) ventricle. Angiotensin converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARB's) are drugs which act as inhibitors of RAAS. Previously, large trials have demonstrated the beneficial effect of angiotensin converting enzyme (ACE) inhibitors on morbidity and mortality in patients with acquired left ventricular (LV) dysfunction. ARB's have a similar effect as ACE inhibitors in patients with acquired LV dysfunction but discontinuation because of side effects such as cough is less frequent. In TOF patients with RV overload due to pulmonary regurgitation, pulmonary valve replacement leads to a decrease in RV size and pulmonary regurgitation. Current guidelines advise empiric use of RAAS inhibitors for right ventricular dysfunction in adult patients with congenital heart disease. However, the actual effect of RAAS inhibition on right ventricular dysfunction in adult TOF patients without severe valvular lesions has not been sufficiently investigated. Therefore, we set-up the proposed study, and hypothesize that ARB's have a beneficial effect on RV ejection fraction in adult TOF patients with RV dysfunction without severe valvular lesions. Objective: to improve RV ejection fraction in adult TOF patients with RV dysfunction without severe valvular lesions. Study design: a prospective, multicenter, double-blind, randomized, placebo-controlled trial. Follow up two years Study population: adult patients with Tetralogy of Fallot with right ventricular dysfunction, defined as right ventricular ejection fraction < 50% and without severe valvular lesions Intervention: patients are randomized to receive either losartan 150 mg once daily, or placebo in the same regimen. Main study parameters/endpoints: the primary endpoint is difference in change in RV ejection fraction, determined by cardiovascular magnetic resonance imaging (CMR), between the treatment and the control group at two years follow-up. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All investigations, except blood analysis, are non-invasive and free of risk. The burden for the patients mainly consists of the time that is consumed by the visits to the clinic. At these visits time will be consumed by: history taking and physical investigation (15 minutes); quality of life score (15 minutes); laboratory tests (6 times venopuncture, total amount of blood withdrawn approximately 90ml). Cardiopulmonary exercise testing (1hour), echocardiography (15 minutes) and CMR (45 minutes) are part of regular medical care. Adverse effects from losartan are usually limited and consist of dizziness due to hypotension, renal impairment, hyperkalemia and liver impairment. We expect no change or an increase in RV function in the intervention group compared to the control group over the two-year follow up period, which would be a great benefit for this young study population. |
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Detailed Description | Not Provided | ||
Study Type ICMJE | Interventional | ||
Study Phase ICMJE | Phase 2 | ||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor) Primary Purpose: Treatment |
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Intervention ICMJE |
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Study Arms ICMJE |
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Publications * | Bokma JP, Winter MM, van Dijk AP, Vliegen HW, van Melle JP, Meijboom FJ, Post MC, Berbee JK, Boekholdt SM, Groenink M, Zwinderman AH, Mulder BJM, Bouma BJ. Effect of Losartan on Right Ventricular Dysfunction: Results From the Double-Blind, Randomized REDEFINE Trial (Right Ventricular Dysfunction in Tetralogy of Fallot: Inhibition of the Renin-Angiotensin-Aldosterone System) in Adults With Repaired Tetralogy of Fallot. Circulation. 2018 Apr 3;137(14):1463-1471. doi: 10.1161/CIRCULATIONAHA.117.031438. Epub 2017 Dec 8. | ||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
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Recruitment Information | |||
Recruitment Status ICMJE | Unknown status | ||
Estimated Enrollment ICMJE |
120 | ||
Original Estimated Enrollment ICMJE | Same as current | ||
Estimated Study Completion Date ICMJE | January 2018 | ||
Estimated Primary Completion Date | January 2018 (Final data collection date for primary outcome measure) | ||
Eligibility Criteria ICMJE | Inclusion Criteria: In order to be eligible to participate in this study, a subject must meet all of the following criteria: adult age and mentally competent; and Tetralogy of Fallot; and right ventricular dysfunction, defined as right ventricular ejection fraction 50% or lower as measured by Cardiovascular Magnetic Resonance Imaging (CMR). Not more than moderate tricuspid or pulmonary regurgitation or more than moderate pulmonary stenosis as measured by CMR or echocardiography. Exclusion Criteria:
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Sex/Gender ICMJE |
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Ages ICMJE | 18 Years to 80 Years (Adult, Older Adult) | ||
Accepts Healthy Volunteers ICMJE | No | ||
Contacts ICMJE | Contact information is only displayed when the study is recruiting subjects | ||
Listed Location Countries ICMJE | Netherlands | ||
Removed Location Countries | |||
Administrative Information | |||
NCT Number ICMJE | NCT02010905 | ||
Other Study ID Numbers ICMJE | NL44943.018.13 | ||
Has Data Monitoring Committee | Yes | ||
U.S. FDA-regulated Product | Not Provided | ||
IPD Sharing Statement ICMJE | Not Provided | ||
Current Responsible Party | Berto J Bouma, Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | ||
Original Responsible Party | Same as current | ||
Current Study Sponsor ICMJE | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | ||
Original Study Sponsor ICMJE | Same as current | ||
Collaborators ICMJE | The Interuniversity Cardiology Institute of the Netherlands | ||
Investigators ICMJE | Not Provided | ||
PRS Account | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA) | ||
Verification Date | December 2015 | ||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |