Journal of Clinical Trials
Open Access

Abstract

A Prospective, Double-blind, Randomised Controlled Trial of the Angiotensin Converting Enzyme Inhibitor Ramipril In Asymptomatic Aortic Stenosis (RIAS trial): Trial Protocol

Sacha Bull, Margaret Loudon, Jane M. Francis, Jubin.Joseph, Stephen Gerry, Theodoros D Karamitsos, Bernard D Prendergast, Adrian P Banning, Stefan Neubauer and Saul G Myerson

Background: The RIAS trial (Ramipril in Aortic Stenosis) is the first randomised, prospective, single centre, double blinded trial to examine the effects of Angiotensin Converting Enzyme (ACE) inhibition in asymptomatic Aortic Stenosis (AS).
Prognosis in AS depends on how the left ventricle responds to pressure overload; severe Left Ventricular Hypertrophy (LVH) carries an adverse prognosis. ACE inhibitors reduce LVH in other conditions and may have similar benefits in patients with AS. The aims of this study were three-fold:
1) To examine the regression of LV mass and changes in other LV physiological parameters using cardiac magnetic resonance (CMR)
2) To assess the safety and tolerability of ramipril in AS
3) To examine the potential improvement in exercise tolerance
Methods: 100 patients with asymptomatic moderate or severe AS will be enrolled. Patients will be randomized to placebo or ramipril (10 mg) for 12 months. At 0, 6 and 12 months, the patients will undergo a clinical assessment, phlebotomy, CMR scanning, echocardiography and a medically supervised Naughton protocol Exercise Test (ETT). Clinic checks at 2, 4, 12 and 14 weeks will be carried to titrate medication and monitor for adverse events.
Results: The primary endpoint of the trial is to measure change in LV mass. Secondary endpoints include changes in LV Ejection Fraction (LVEF), diastolic function parameters, perfusion, biochemical markers of LV function and exercise tolerance.
Conclusion: The RIAS trial is the first randomised, prospective, double blind trial to examine the effects of ACE inhibition in AS. If the trial is positive, our study would form the basis for a larger clinical outcome trial.
Trial registration: International Standard Randomised Controlled Trial Number 24616095