A Study of Angiotensin-II Receptor Blocker on Cardiovascular Remodeling (VALUE Trial)

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the effectiveness and mechanism of action of Losartan in the treatment of coarctation of aorta.

Official Title
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A Phase III, Randomized, Double-Blind, Placebo Controlled Clinical Trial Evaluating the Benefits and Mechanism Of Action Of Angiotensin-II Receptor Blocker On Cardiovascular Remodeling In Patients With Repaired Coarctation Of Aorta

Conditions
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Coarctation of Aorta, High Blood Pressure

Intervention / Treatment
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* Drug: Losartan
* Drug: Amlodipine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: B/S1 hypertension; SBP 120-139 average based on 3 office measurements. COA Repair prior to age 10 No residual COA; Based on mean doppler COA gradient <20mmHg within past 12 months Exclusion Criteria: Currently on beta blocker (BB) therapy Pregnancy/lactating eGFR<30 Hyperkalemia (serum potassium >5.5mmol/L) Severe Aortic or Mitral valve stenosis or regurgitation Epicardial CAD diagnosis Received antihypertensive medications within the past year

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Losartan Group<br>Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Losartan. | Drug: Losartan<br>* 50mg administered orally once daily for 52 weeks.<br>* Other names: Cozaar;|
| Active Comparator: Amlodipine Group<br>Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Amlodipine. | Drug: Amlodipine<br>* 5mg Amlodipine administered orally once daily for 52 weeks.<br>|
| Placebo Comparator: Placebo Group<br>Subjects with Coarctation of Aorta (COA) and high blood pressure will receive Placebo. | Drug: Placebo<br>* Oral capsules that contain no active drug ingredients administered orally once daily for 52 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Left Ventricular (LV) Fibrosis | LV fibrosis will be measured via indexed Extracellular Volume (iECV) which will be calculated as extracellular volume fraction (ECV%) x LV End Diastolic Volume Index as evaluated during Cardiac Magnetic Resonance Imaging (CMRI). | Baseline; Week 52 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Exercise Capacity (peak VO2) | Change in Exercise Capacity will be evaluated based on peak VO2, measured as milliliters of oxygen per kilogram of body weight per minute (ml/kg/min), during supine bike cardiopulmonary exercise test (Stress Echocardiogram). | Baseline; Week 52 |