Double-blind Parallel Placebo-controlled Study to Evaluate the Effect of Molsidomine on the Endothelial Dysfunction in Patients With Stable Angina Pectoris Undergoing a Percutaneous Coronary Intervention
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 165
- 试验地点
- 1
- 主要终点
- Change Versus Baseline in the Score of the EndoPAT in the Two Groups After One Year of Treatment (Month 12).
研究概览
简要总结
Molsidomine used as an add-on treatment on standard care therapy should be superior to placebo used also as an add-on treatment on standard care therapy on improving the endothelial function (endothelium score measured by reactive hyperemia - peripheral arterial tonometry [RH-PAT]) after 12 months of treatment in patients with stable angina patients and undergoing elective percutaneous coronary intervention.
The study will be double-blind, parallel-group, randomised, multicentre, sequential, placebo-controlled study.
The device used to determine RH-PAT will be EndoPAT. Duration of the treatment = one year.
详细描述
A Data Steering Committee (DSC) will blindly assess the recruitment rate, the variability of RH-PAT within and between centres, and the safety on a regular basis.
Sequential approach:
- In the first phase (Phase A) of the study, 180 patients will be enrolled in order to get at least 50 completers after 12 months of treatment. A statistical evaluation of the primary endpoint will be done by an Independent Biostatistician after approximately 50 patients have completed the study in accordance with the protocol.
- The results will be examined by an Independent Data Monitoring Committee (IDMC)which will assess the results and advise the sponsor as to:
- Continue the study if the primary objective has not been achieved but the difference between the two groups is at least 10% (difference considered clinically significant). In this case, the sample size will be recalculated by the Independent Biostatistician taking into account actual difference and variability. The total number of patients to be enrolled in addition in Phase B will be calculated with precision. Depending on IDMC recommendations, the number of investigating centres will be increased or not for Phase B. If the right number of patients has already been enrolled, Phase B will not start. The study will stop when all enrolled patients have completed the one-year treatment period.
- 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.
Treatment allocation: Balanced allocation between molsidomine and placebo (1:1) with a stratification for consumption of statins, for the type of stent (drug-eluting stent or bare-metal) and for consumption of angiotensin-converting enzyme inhibitors (ACEIs).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 percutaneous coronary intervention (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.
- •Patients who underwent PCI for stable angina pectoris one month prior to the start of the study.
- •Patients presenting endothelial dysfunction at Month 0 (score of the Endo-PAT <0.40).
排除标准
- •Pre-menopausal women.
- •Patient with a clinically-active malignancy.
- •Known major renal insufficiency or known significant hepatic insufficiency.
- •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: creatine kinase-muscle/brain (CK-MB) >3 times the upper reference limit.
- •Clinically significant abnormal pre-PCI CK-MB and troponin: any elevation above the upper reference limit.
- •Intolerance to galactose, deficiency in Lapp lactase or glucose-galactose malabsorption.
- •Left ventricular insufficiency (New York Heart Association [NYHA] class III or IV) with an ejection fraction <35%.
- •Acute circulatory insufficiency (e.g. cardiogenic shock).
- •Hypotension: systolic blood pressure <100 mmHg and/or diastolic blood pressure <70 mmHg.
- •Atrial fibrillation
- •Acute myocardial infarction during the preceding month.
- •Unsuccessful PCI: residual stenosis of at least 50%.
- •Patient taking phosphodiesterase-5 inhibitors, such as sildenafil (Viagra®), vardenafil (Levitra®) and tadalafil (Cialis®)
- •Patient taking nebivolol (Nobiten®)
- •Patient taking ibuprofen + L-arginine as excipient (Spidifen®)
- •Patient meeting any contraindication(s) from Coruno®. Please refer to Coruno® (molsidomine 16 mg o.d.)Summary of Product Characteristics (SPC).
研究组 & 干预措施
Molsidomine
Coruno (molsidomine 16 mg tablet; per os; once daily)
干预措施: Coruno (Drug)
Placebo
Placebo (16 mg tablet; once a day)
干预措施: Placebo (Drug)
结局指标
主要结局
Change Versus Baseline in the Score of the EndoPAT in the Two Groups After One Year of Treatment (Month 12).
时间窗: 12 months
The results are expressed mean relative change (%) between month 12 and baseline. A positive result means improvement in the score of the EndoPAT between baseline and month 12. It could be considered as a surrogate of a decrease of the endothelial dysfunction. A negative percentage means the inverse. The are no fixed limits to the scale. The minimum observed was -275% and the maximum observed was +4200%.
次要结局
- Change Versus Baseline in the Augmentation Index in the Two Groups After Six and Twelve Months of Treatment (Months 6 and 12).(Month 6 and Month 12)
- Frequency of AEs and SAEs in the Two Groups After Twelve Months of Treatment (Month 12).(Month 12)
- Frequency of Serious Cardiovascular Events (SCEs) in the Two Groups After Twelve Months of Treatment (Month 12).(Month 12)
- Change Versus Baseline in the Score of the EndoPAT in the Two Groups After Six Months of Treatment (Month 6).(Month 6)
- Change Versus Baseline in Some Specific Endothelial Biomarkers After Twelve Months of Treatment (Month 12).(Month 12)