E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Randomized, double-blind, placebo-controlled, add-on study in two parallel groups. Patients admitted for Non ST Segment Elevation Acute Coronary Syndromes will undergo a coronary angiography according to the guidelines and, if indicated, an eluting stent implantation. During angiography, a triple-vessel intravascular ultrasonography (IVUS) and virtual histology reconstruction will be performed. |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 7.0 |
E.1.2 | Level | HLT |
E.1.2 | Classification code | 10011085 |
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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 objective of this study is to evaluate the potential effect of molsidomine 16 mg o.d. on atherosclerosis progression in coronary patients and to seek for a link with the plasma levels in biomarkers of vascular wall inflammation. The primary composite endpoint is to compare atherosclerotic plaque composition under placebo and under molsidomine 16 mg o.d., administered as add-on therapy, in patients hospitalized for NSTE-ACS by using the combined IVUS and VH reconstruction techniques. This analysis will focus on the evolving of lesions in non-culprit segments, in any of the coronary arteries studied at baseline. Primary endpoints will be : - dense calcium, fibrotic plaque, fibrofatty plaque, and necrotic core % of total plaque in at most 4 regions of interest (ROI) - dense calcium, fibrotic plaque, fibrofatty plaque, and necrotic core % of total VH in at most 4 ROI
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E.2.2 | Secondary objectives of the trial |
- to compare total atherosclerotic plaque burden under placebo and under molsidomine 16 mg o.d. by using the combined IVUS, VH and palpography techniques; - to seek for a correlation between the rate of atherosclerosis progression and the levels of hs-CRP, sICAM-1 and other biomarkers at baseline, i.e. at day-1 and /or at visit 1; - to seek for a correlation between the rate of atherosclerosis progression and changes in levels of hs-CRP, sICAM-1, and other biomarkers; - to compare the rate of recurrent cardiac events under placebo and under molsidomine occurring from 1 week post-randomization (cardiac events to be taken into account are recurrent - pectoris, recurrent myocardial infarction unrelated to the treated vessel(s), severe arrhythmia, heart failure, hospitalization for cardiac reason, need for further myocardial revascularization [PTCA, CABG] and cardiac death); |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
- Patient who just underwent coronary angiography for NSTE-ACS. - Patient whose ultrasonogram meets predefined quality criteria requirements. - Patient aged ≥ 18 years. - Patient to whom no NO donor, like -long-acting nitrates or molsidomine, was administrated prior to hospitalization.
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E.4 | Principal exclusion criteria |
- Female of childbearing age. - Heart failure NYHA III or IV. - Any serious concomitant disorder that could possibly interfere with the clinical evaluation, such as C.O.P.D. or severe anemia. - Active infection or inflammatory process. - Treatment by anti-inflammatory drugs. - Patient with malignancy. - Treatment by drugs for erection disturbances containing phosphodiesterase-5 inhibitors such as sildenafil (Viagra®), vardenafil (Levitra®) and tadalafil (Cialis®). - Known major renal insufficiency (creatinine ≥ 2.0 mg/ml) or known significant hepatic i nsufficiency (SGOT ≥ 2 times upper limit, total bilirubin ≥ 1.5 times upper limit). - History of psychological disorder, mental dysfunction, alcohol or drug abuse or any other factor which might interfere with the ability to cooperate in the study. - Inability to provide informed consent. - Participation in another clinical study during the last previous month.
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E.5 End points |
E.5.1 | Primary end point(s) |
The primary composite endpoint is to compare atherosclerotic plaque composition under placebo and under molsidomine 16 mg o.d., administered as add-on therapy, in patients hospitalized for NSTE-ACS by using the combined IVUS and VH reconstruction techniques. This analysis will focus on the evolving of lesions in non-culprit segments, in any of the coronary arteries studied at baseline. Primary endpoints will be : - dense calcium, fibrotic plaque, fibrofatty plaque, and necrotic core % of total plaque in at most 4 regions of interest (ROI) - dense calcium, fibrotic plaque, fibrofatty plaque, and necrotic core % of total VH in at most 4 ROI
Only patients who meet predefined quality requirements will eventually be enrolled.
Predefined quality requirements include:
• Good quality coronary angiography after intracoronary nitrates • availability of good quality baseline IVUS • IVUS pull-back (0.5 mm/sec) over at least 3 cm from the coronary ostium • IVUS examination of all coronary arteries is encouraged |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Information not present in EudraCT |
E.6.3 | Therapy | Information not present in EudraCT |
E.6.4 | Safety | Information not present in EudraCT |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Information not present in EudraCT |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Yes |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
E.7.4 | Therapeutic use (Phase IV) | Information not present in EudraCT |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
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 | 3 |
E.8.5 | The trial involves multiple Member States | Information not present in EudraCT |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Information not present in EudraCT |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
E.8.7 | Trial has a data monitoring committee | No |
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 | |
E.8.9.1 | In the Member State concerned days | |