E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Progression of atherosclerosis in patients with coronary artery disease |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 9.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011093 |
E.1.2 | Term | Coronary atherosclerosis |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
The primary objective of this study is: To evaluate the effect of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo on progression of coronary atherosclerosis (defined as change from baseline in percent atheroma volume) as assessed by IVUS in patients with CAD and blood pressure in the pre-hypertensive (high normal) range with or without treatment for hypertension. |
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E.2.2 | Secondary objectives of the trial |
To evaluate the efficacy profile of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo on the change in normalized total atheroma volume as assessed by IVUS. To evaluate the efficacy profile of aliskiren 300 mg, in addition to optimized background therapy, compared to placebo, by comparing the proportion of patients who demonstrate evidence of atheroma regression (defined as any reduction in percent atheroma volume from baseline) as assessed by IVUS. To evaluate the overall safety and tolerability of aliskiren 300 mg compared to placebo in patients with CAD and blood pressure in the pre-hypertensive (high normal) range with or without treatment for hypertension following 104 weeks of treatment. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
1. Patients must give written informed consent before any study related assessments are performed. 2. Male and female patients &#8805; 35 years of age who are scheduled for a coronary catheterization procedure for a clinically indicated reason at Visit 1. 3. Patients with or without current treatment for hypertension must have a msSBP &#8805; 125 and &#8804; 139 mmHg and an msDBP < 90 mmHg at Visit 2. For those patients receiving treatment for hypertension, every effort should be made by the Investigator to have the patient on a stable dose (defined as dose unchanged for &#8805; 1 week) of medication prior to Visit 2. 4. Patients must have at least two of the following risk factors present at Visit 1: History of prior myocardial infarction (MI), acute coronary syndrome (ACS) or previous coronary or peripheral revascularization. No prior treatment with a statin medication. If the patient has been previously treated at any time with a statin medication, it must be for a period of &#8804; 3 months in the 12 months prior to Visit 1. HDL < 40 mg/dL (1.0 mmol/L) for men or < 50 mg/dL (1.3 mmol/L) for women OR triglycerides > 150 mg/dL (1.7 mmol/L) within 3 months of Visit 1 or at Visit 1. Microalbuminuria [defined as UACR &#8805; 30 mg/g and < 300 mg/g (&#8805; 3.4 mg/mmol and < 33.9 mg/mmol)] OR macroalbuminuria [defined as UACR &#8805; 300 mg/g and < 3000 mg/g (&#8805; 33.9 mg/mmol and < 339.3 mg/mmol)] within 3 months of Visit 1 or at Visit 1. Age > 55 years. Diagnosis of diabetes mellitus based on medical history, concomitant diabetic medications being taken at study entry OR a fasting plasma glucose (FPG) > 126 mg/dL (7.0 mmol/l ) or non fasting plasma glucose > 200 mg/dL (11.1 mmol/L) or HbA1c > 6.0 % at Visit 1. Current smoking within 4 weeks of Visit 1 or at Visit 1. History of LVH documented by ECG, echocardiogram or MRI performed &#8804; 6 months prior to Visit 1. 5. Patients must meet all of the following criteria at the qualifying coronary catheterization procedure: Entire Coronary Circulation: Angiographic evidence of coronary heart disease as defined by at least one lesion in any of the three major native coronary arteries that has > 20% reduction in lumen diameter by angiographic visual estimation or prior history of PTCA. This vessel need not be the target coronary artery for IVUS (defined below). Any vessel with previous PTCA may not be used as the target coronary artery. Left Main Coronary Artery: Must not have a > 50% reduction in lumen diameter by visual angiographic estimation. PLS SEE PROTOCOL |
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E.4 | Principal exclusion criteria |
1. Baseline IVUS study determined to be of unacceptable quality by the IVUS Core laboratory in accordance with the lab manual guidelines for acquisition and analysis of IVUS imaging prior to Visit 2. 2. Patients requiring continued treatment with any 2 of the following classes of medications at Visit 1 or Visit 2: ACEIs, ARBs, aldosterone receptor blockers or a direct renin inhibitor. 3. Patients with clinically significant heart disease, which in the opinion of the Investigator is likely to require coronary bypass surgery, PCI in the target vessel, surgical repair, ventricular assist device placement, cardiac transplantation, or require intra-aortic balloon pump support during the duration of the study. 4. Patients who experience restenosis, a myocardial infarction or suspected myocardial infarction between the baseline IVUS (Visit 1) and Visit 2 can only be entered into the single-blind period of the study if the affected vessel is not the coronary artery designated as the target vessel at the baseline IVUS study. If the target vessel is involved, the patient must be discontinued from the screening phase of the study prior to Visit 2. 5. Previous or current diagnosis of heart failure (NYHA Class IV) or a documented left ventricular ejection fraction (LVEF) of < 25% as determined by contrast left ventriculography, radionuclide ventriculography or echocardiography. The absence of an LVEF measurement in a patient without a previous or current diagnosis of heart failure does not prohibit entry into the study. 6. Patients with evidence of cardiac electrophysiologic instability including a history of uncontrolled ventricular arrhythmias, uncontrolled atrial fibrillation/flutter or uncontrolled supraventricular tachycardia with a ventricular response heart rate of > 100 beats per minute at rest within 4 weeks prior to Visit 1. 7. Coronary artery bypass graft surgery &#8804; 6 weeks of the date of the qualifying IVUS procedure. 8. Evidence of renal impairment as determined by any one of the following: Estimated Glomerular Filtration Rate (eGFR) < 40 ml/min/1.73 m2 using the MDRD formula at Visit 1 and Visit 2. A history of dialysis, macroalbuminuria (defined as a UACR &#8805; 3000 mg/g) or nephrotic syndrome. 9. History or evidence of a secondary form of hypertension. 10. Known Keith-Wagener grade III or IV hypertensive retinopathy. 11. History of hypertensive encephalopathy, cerebrovascular accident or transient ischemic cerebral attack (TIA) within 12 months of study entry. PLS SEE PROTOCOL |
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary endpoint variable of this study is the change from baseline in percent atheroma volume (PAV)for all matched slices of anatomically comparable segments of the target coronary artery as assessed by IVUS evaluation after 104 weeks of treatment (single-blind and double-blind) |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | No |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 12 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 48 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
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E.8.7 | Trial has a data monitoring committee | Yes |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |