Blocking the Effects of Serotonin to Prevent Ischemic Mitral Regurgitation: a Randomized Trial (CYPRO-MR)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 214
- 试验地点
- 1
- 主要终点
- Change in mitral regurgitation severity
研究概览
简要总结
This study is intended to investigate the effect of cyproheptadine (a 5HT2B receptor blocker) on mitral regurgitation severity.
详细描述
Ischemic mitral regurgitation (MR) is a common and morbid complication of myocardial infarction (MI), doubling heart failure and mortality with currently limited therapies. Its mechanisms have been previously linked to left ventricle (LV) remodeling with secondary deformation of otherwise normal mitral leaflets. Recent studies are introducing new mechanistic elements, allowing possibilities for potential pharmacotherapeutic approaches. Normal mitral leaflets have the capacity to enlarge and adapt to even the largest LV dilatation to prevent MR. However, this compensatory mechanism is insufficient after MI, and the leaflets are abnormally thick with fibrotic changes. Those fibrotic changes could be related to a variation in blood serotonin (5-HT) levels after MI, which has been previously reported. Serotonin is a known cause of valve fibrosis through its 5HT type 2B receptor. In sheep models, the investigators have tested the hypothesis that a 5HT type 2B receptor blocker (cyproheptadine) can prevent adverse remodeling in the valve after MI. Cyproheptadine treatment was associated with increased valve leaflet surface, attenuated leaflet thickening and collagen deposition. Importantly, treated animals had less MR compared to non-treated animals.
Thus the present study is a double-blind randomized trial to assess the effect of cyproheptadine on MR severity, mitral valve surface variation, and left ventricular size following MI. Serial imaging (3D echo and MRI) will assess valve adaptation, LV remodeling and MR.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients 18-80 years old with a 1st episode of STEMI with documented coronary obstruction.
- •Left ventricle ejection fraction (LVEF)<50% and mitral tenting area ≥ 4 cm2, OR LVEF ≤ 40% and inferior/posterior wall motion anomaly, OR LVEF≤30% and wall motion in any territory.
排除标准
- •Inability to provide informed consent
- •Hemodynamic instability / cardiogenic shock / papillary muscle rupture
- •Prior mitral valve procedure/surgery
- •Permanent atrial fibrillation (limiting imaging and MR quantification)
- •Primary mitral disease (endocarditis, rheumatic, degenerative or congenital)
- •More than mild valvular disease (other than mitral) at baseline
- •Planned cardiac surgery (CABG or valve intervention) within 3 months
- •Contraindications for MRI
- •Ongoing treatment with selective serotonin reuptake inhibitor (SSRI)
- •Chronic use of sedative medication
- •Ongoing or planned pregnancy
- •Chronic renal failure with Estimated Glomerular Filtration Rate (eGFR) < 30 mL/min
- •Neurocognitive disorder
- •Symptom or prior episode of urinary obstruction or glaucoma (relative contraindications for cyproheptadine)
研究组 & 干预措施
Cyproheptadine 4 Mg Oral Tablet
Participants will receive cyproheptadine 4mg tablet orally three times a day for three months, with a daily increase of 4mg/dose if the previous dose was well tolerated, up to 0.5 mg/kg/day.
干预措施: Cyproheptadine 4 Mg Oral Tablet (Drug)
Placebo
Participants will receive a matched placebo orally three times a day for 3 months. Daily titration similar to the treatment arm.
干预措施: Placebo (Other)
结局指标
主要结局
Change in mitral regurgitation severity
时间窗: Baseline, 3 months
Incidence of more than mild MR (MRI regurgitant fraction ≥ 20%) at 3 months (measured by MRI)
次要结局
- Change in left ventricle function(Baseline, 3 months)
- Change in mitral valve thickness(Baseline, 3 months)
- Ischemic events(3 months and 1 year)
- Bleeding events(3 months and 1 year)
- Change in weight of participants(Baseline, 3 months)
- Change in the patient's perception of their health status(Baseline, 3 months)
- Change in the functional capacity of participants(3 months, 1 year)
- Incidence of sedation(Baseline, 3 months)
- Change in mitral leaflet size(Baseline, 3 months)
- Change in mitral regurgitation grade(Baseline, 3 months)
- Change in left ventricle size(Baseline, 3 months)
- Incidence of other valve regurgitation(3 months)
- Adverse events(3 months and 1 year)
- Change in depression score(Baseline, 3 months)