E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Patients with stable angina undergoing elective PCI, used an add-on treatment on standard care therapy, molsidomine or placebo to improve the endothelial function (12 months treatment) |
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E.1.1.1 | Medical condition in easily understood language |
Study versus placebo to estimate the effect of molsidomine on the endothelial dysfunction in patients presenting a stable angina pectoris and undergoing a percutaneous coronary intervention. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10011079 |
E.1.2 | Term | Coronary artery disease NOS |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 14.1 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10007541 |
E.1.2 | Term | Cardiac disorders |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
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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 |
To demonstrate in stable angina patients undergoing elective PCI the superiority of molsidomine, used as an add-on treatment on standard care therapy, over placebo on improving the endothelial function (Endoscore measured by RH-PAT) after 12 months of treatment. |
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E.2.2 | Secondary objectives of the trial |
To estimate the effect of molsidomine and placebo on the augmentation index (an index of arterial stiffness) as measured by RH-PAT.
To determine the impact of molsidomine on the following endothelial biomarkers:
hs-CRP
sICAM-1
IL-8
Myeloperoxidase (in terms of concentration and activity)
Myeloperoxidase oxidized-LDL (MOx-LDL)
Isoprostanes
Microparticles from the endothelium, leukocytes and platelets
To compare the rate of serious cardiovascular events (SCEs) in the two groups.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
All patients must satisfy ALL the following criteria at study entry (Visit 1 - Month -1):
• Aged at least 18 years.
• No treatment with molsidomine and/or long-acting nitrates (oral or patches) for more than 48 hours during the month preceding PCI and no treatment with these same drugs within 3 days before PCI.
• Patients who the investigator believes that they and/or their Legally Acceptable Representative (LAR) can and will comply with the requirements of the protocol.
• Written informed consent from the patient or from the LAR.
All patients must satisfy the following criterion at randomisation (Visit 2 - Month 0):
• Patients who underwent PCI for stable angina pectoris one month prior to the start of the study (30 7 days).
• Patients presenting ED at Month 0 (Endoscore index <0.40) (Rubinshtein et al., 2009).
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E.4 | Principal exclusion criteria |
• Pre-menopausal women.
• Patient with a clinically-active malignancy.
• Known major renal insufficiency (creatinine 2.0 mg/ml) or known significant hepatic insufficiency (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.
• Participation in another clinical trial which has not yet reached its primary endpoint or with the same primary endpoint during the previous month.
• Concurrently participating in another clinical study, at any time during the study period, in which the subject will be exposed to an investigational or a non-investigational product (vaccine, drug or device).
• Hypersensitivity to molsidomine or to one of its excipients.
• Peri-procedural infarction: CK-MB >3 times the upper reference limit (Thygesen et al., 2007).
• Clinically significant abnormal pre-PCI CK-MB and troponin: any elevation above the upper reference limit (Thygesen et al., 2007).
• Intolerance to galactose, deficiency in Lapp lactase or glucose-galactose malabsorption.
• Left ventricular insufficiency (NYHA class III or IV) with an ejection fraction <35%.
• Acute circulatory insufficiency (e.g. cardiogenic shock).
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E.5 End points |
E.5.1 | Primary end point(s) |
Change versus baseline in the Endoscore index in the two groups after one year of treatment (Month 12). |
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
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E.5.2 | Secondary end point(s) |
• Change versus baseline in the Endoscore index in the two groups after six months of treatment (Month 6).
• Change versus baseline in the augmentation index in the two groups after six and twelve months of treatment (Months 6 and 12).
• Change versus baseline in the endothelial biomarkers (see Secondary objectives section) after six and twelve months of treatment (Months 6 and 12).
• Frequency of serious cardiovascular events (SCEs) in the two groups after six and twelve months of treatment (Months 6 and 12).
• Frequency of AEs and SAEs in the two groups after six and twelve months of treatment (Months 6 and 12).
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
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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 | No |
E.6.5 | Efficacy | No |
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 | Yes |
E.6.13.1 | Other scope of the trial description |
Effect on endothelial dysfunction in patient in stable angina pectoris |
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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) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
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.8.2.4 | Number of treatment arms in the trial | 2 |
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 | 11 |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
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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Phase A: The IDMC will advise the sponsor as to:
- terminate the study, if the difference between the two groups is less than 10%.
- Consider the study as completed if the primary endpoint has been achieved.
Phase B: In all the other case, the study will proceed to Phase B.
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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 | 0 |