Sildenafil for Improving Outcomes After Valvular Correction
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 200
- 试验地点
- 18
- 主要终点
- Combined Outcome End-Point: all-cause mortality or hospital admission for heart failure, worsening of World Health Organization (WHO) functional class, or of the patient global assessment score
研究概览
简要总结
The purpose of this study is to evaluate the clinical efficacy of the mid-term treatment with sildenafil in patients with persistent moderate or severe pulmonary hypertension (PH) after a heart valve intervention.
详细描述
Phase IV, prospective, multicenter, randomized, double-blind, placebo-controlled, academically funded clinical trial, with 6 months follow-up. A total of 354 patients will be recruited. Inclusion criteria are: 1) successful surgical or percutaneous repair of a cardiac valve at least one year before screening and 2) persistent moderate or severe PH, and 3) absence of any residual significant valvular lesion. Patients will be randomized 1:1 to received sildenafil 40 mg t.i.d. or placebo. The primary endpoint is a clinical composite score combining: all-cause mortality, hospital admission for heart failure, World Health Organization (WHO) functional class, and the patient global assessment score. Additional clinical and mechanistic secondary end-points are defined.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
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
- •Age at the date of selection ≥ 18 years
- •Mean pulmonary pressure ≥ 30 mmHg, measured by a Swan-Ganz catheter placed in the pulmonary artery
- •Heart valve intervention: surgical or percutaneous replacement, repair or dilatation performed at least one year before inclusion
- •Stable clinical condition for at least one month, without hospital admissions for heart failure, and on appropriate and stable doses of conventional cardiovascular medications
排除标准
- •Requiring or likely to require the following medications: organic nitrates, alpha-blocker therapy, potent cytochrome P450 3A4 inhibitors (erythromycin, ketoconazole, cimetidine, HIV protease inhibitors such ritonavir and saquinavir) Patients who have suffered a myocardial infarction, stroke, or life-threatening arrhythmia within the last 6 months.
- •Patients with resting hypotension, with systolic blood pressure < 90 mmHg
- •Patients with retinitis pigmentosa
- •Anatomical deformation of the penis (such as angulation, cavernosal fibrosis or Peyronie's disease) or patients who have conditions which may predispose them to priapism (such as sickle cell anemia, multiple myeloma, or leukemia)
- •Severe renal impairment with creatinine clearance < 30 ml/min
- •Significant hepatic dysfunction
- •Prosthesis or valvular dysfunction with hemodynamic repercussion.
- •Pregnant or breast-feeding women
- •Patients unlikely to cooperate in the study or with inability or unwillingness to give informed consent
- •Life expectancy less than 2 years due to non-cardiac disease
研究组 & 干预措施
Sildenafil Citrate
Sildenafil Citrate 40 mg t.i.d. oral
干预措施: Sildenafil Citrate (Drug)
Placebo
Sildenafil-matched oral placebo 40 mg t.i.d
干预措施: Placebo (Drug)
结局指标
主要结局
Combined Outcome End-Point: all-cause mortality or hospital admission for heart failure, worsening of World Health Organization (WHO) functional class, or of the patient global assessment score
时间窗: Six months
次要结局
- Change from baseline to the sixth month in the in the six-minute walk test(6 Months)
- All cause mortality(6 Months)
- Cardiovascular mortality(6 months)
- Number of hospital admissions caused by or related to heart failure in each patient(6 months)
- Rate of progression/regression of tricuspid regurgitation by Doppler-echocardiography(3 & 6 Months)
- Change on right ventricular (RV) dimensions and function assessed by Doppler echocardiography(3 & 6 months)
- Change on RV volumes and function assessed by cardiac magnetic resonance(6 Months)
- Change on the right catheterization hemodynamic parameters(6 Months)
- Identify patients who are more likely to respond to therapy by pharmacogenetics analysis(6 Months)
- Change on WHO functional capacity(3 & 6 Months)