Effect of Phosphodiesterase-5 Inhibition With Tadalafil on SystEmic Right VEntricular Size and Function - a Multi-center, Double-blind, Randomized, Placebo-controlled Clinical Trial - SERVE Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 7
- 主要终点
- Systemic right ventricle endsystolic volume
研究概览
简要总结
This study assesses in a double-blind, randomized, placebo-controlled multi-center pilot trial the effect of PDE-5 inhibition with Tadalafil on right ventricle size and function, exercise capacity and neurohumoral activation in adults with congenital heart disease and a right ventricle in subaortic position over a 3-year follow-up period.
详细描述
Currently, there are an estimated 300-600 adults living in Switzerland with congenital heart disease (CHD) and a right ventricle (RV) in subaortic (systemic) position. This includes adults with prior atrial switch operations for complete transposition of the great arteries (D-TGA) and adults with congenitally corrected transposition of the great arteries (ccTGA). Although midterm survival is favourable, late outcome is compromised by ventricular dysfunction of the systemic RV, end-stage heart failure, and premature death. Medical heart failure therapy (ACE-inhibitors, beta-blockers, aldosterone antagonists) has been shown to improve ventricular function and survival in patients with left heart failure from acquired heart disease. Unfortunately, case-reports and studies failed to show similar clinical benefits of these drugs in adults with a failing systemic RV. Currently, the only established end-stage therapy for a failing systemic RV is heart transplantation. Given the ubiquitous shortage of donor organs and the number of adults at risk, medical options to improve the fate of patients with a systemic RV are urgently needed.
The RV and left ventricle (LV) have different embryological origins, myocardial architecture and contractile properties. In response to increased afterload, as in an RV in systemic position, the RV expresses a fetal gene pattern, with an increase in phosphodiesterase (PDE)-5 expression. PDE-5 is not expressed in the normal RV, but is up-regulated in the hypertrophied RV. PDE-5 inhibition increases contractility in experimental models of RV hypertrophy, but not in the normal RV. In clinical practice, the effects of PDE-5 inhibition on systemic RV function and exercise capacity in adults with TGA have not been tested.
This study assesses in a double-blind, randomized, placebo-controlled multi-center pilot trial the effect of PDE-5 inhibition with Tadalafil on RV size and function, exercise capacity and neurohumoral activation in adults with a systemic RV over a 3-year follow-up period.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 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
- •Systemic right ventricle due to prior atrial switch operations for complete transposition of the great arteries (D-TGA) due to congenitally corrected transposition of the great arteries (ccTGA).
排除标准
- •Incapability of giving informed consent
- •Myocardial infarction, stroke, or open heart surgery within the 3 months prior to baseline visit
- •Expected heart transplant within the next 6 months starting from baseline
- •Pregnant or nursing women (a pregnancy test is mandatory prior to randomization; women of childbearing potential must agree to use reliable contraception from randomization to end of study treatment)
- •Severe renal insufficiency (Creatinine clearance ≤ 30 ml/min)
- •Severe hepatic insufficiency (Child-Pugh-Class C)
- •Hypotension with blood pressures < 90/50 mmHg at the baseline visit
- •Hypersensibility to Tadalafil
- •Allergy to iodinated (in patients undergoing CMDCT) or Gadolinium-based (in patients undergoing CMR) contrast agents.
- •Co-medication with nitrates
- •Regular use of "poppers", i.e. alkyl nitrites, that are inhaled for recreational purposes, including as club drugs used at dance clubs.
- •Co-medication with potent CYP3A4 inhibitors: Ketoconazole, Ritonavir, Rifampicin
- •Co-medication with other PDE-5 inhibitors for erectile dysfunction during the last four weeks prior to baseline visit
- •Medical history of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION)
- •Hereditary Galactose intolerance, Lactase deficiency or Glucose-Galactose-Malabsorption
- •Participation at another clinical trial in which the primary endpoint has not been reached.
研究组 & 干预措施
Tadalafil
Tadalafil 20 MG, p.o., once per day for 3 years
干预措施: Tadalafil 20 MG (Drug)
Placebo
Placebo 20 MG, p.o., once per day for 3 years
干预措施: Placebo 20 MG (Drug)
结局指标
主要结局
Systemic right ventricle endsystolic volume
时间窗: 3 years
Assess of the improvement of Tadalafil on systemic right ventricle endsystolic volume measured by cardiovascular magnetic resonance imaging (CMR) or cardiac multirow detector computed tomography (CMDCT) in patients with contraindications for cardiac MRI
次要结局
- Systemic right ventricle ejection fraction(3 years)
- Serum neurohormonal activation(3 years)
- Cardiopulmonary exercise capacity(3 years)