NCT02744339已完成2 期
Evaluation of the Pharmacodynamic Effects of Riociguat in Subjects With Pulmonary Hypertension and Heart Failure With Preserved Ejection Fraction in a Randomized, Double Blind, Placebo Controlled, Parallel Group, Multicenter Study
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 118
- 试验地点
- 1
- 主要终点
- Change from baseline of cardiac output at rest, measured by right heart catheterization
研究概览
简要总结
The primary objective of this study is to
• Assess the pharmacodynamic profile of riociguat in subjects with symptomatic pulmonary hypertension and heart failure with preserved ejection fraction
The secondary objectives of this study are to
- Assess safety and tolerability of riociguat in this study population
- Assess changes in dimensions of left and right ventricles and cardiac function parameters using cardiac magnetic resonance imaging
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
- Double (Participant, Investigator)
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
- •18 to <80 years of age at the time of informed consent (The lower age limit may be higher if legally required in participating countries.)
- •Male and female subjects with symptomatic PH and HF-PEF (group 2 / 2.2 of Dana Point classification(4) and WHO class II to IV) (Other groups of PH, especially HF-REF, PAH, CTEPH, must have been ruled out according to accepted diagnostic procedures and guidelines, see section 5.1.2 Exclusion criteria.)
- •PH-HF-PEF defined as:
- •LVEF ≥50%, diagnosed by echocardiography or left heart catheterization (LHC) within 30 days before randomization
- •PAPmean ≥25 mmHg at rest, measured by RHC
- •PAWP >15 mmHg at rest, measured by RHC
- •Optimized therapy for hypertension
- •The dose regimen of the background treatment must have been stable for >30 days before randomization. Diuretic therapy must have been stable for ≥1 week.
- •RHC results for the definite diagnosis of PH not older than 12 weeks at Visit
- •RHC must have been performed in the participating center under standardized conditions
- •CMRI must be performed at Visit 1 (baseline) or must not be older than 12 weeks with all parameters measured as listed in Section 7.3.3
- •Women are eligible if not of childbearing potential, defined as:
- •Postmenopausal women (i.e. last menstrual bleeding at least 2 years before randomization)
- •Women with bilateral tubal ligation
- •Women with bilateral ovariectomy
- •Women with hysterectomy or, if of childbearing potential, women are eligible if
- •A serum pregnancy test is negative at the pre-study visit, and The woman uses a combination of condoms and a safe and highly effective contraception method (hormonal contraception with implants or combined oral contraceptives, certain intrauterine devices) for the entire duration of the study.
- •Able to understand and follow instructions and to participate in the study for its entire duration
- •Written informed consent
排除标准
- •PH in groups other than group 2.2 according to Dana Point classification.(4) In particular, PAH, CTEPH, and HF-REF must have been ruled out according to accepted diagnostic procedures and guidelines.
- •Cardiac decompensation, with hospitalization or visit to the emergency department,
- •≤30 days before randomization
- •Left heart disease because of to ischemic heart disease or dilated cardiomyopathy
- •Resynchronization therapy at any time
- •Need for intravenous (IV) diuretics ≤30 days before randomization
- •Treatment with inotropes or IV vasodilators ≤30 days before randomization
- •Pre-treatment with endothelin receptor antagonists (ERAs), phosphodiesterase type 5 (PDE5) inhibitors, or prostanoids ≤30 days before randomization, or with nitrates ≤7 days before randomization
- •Subjects who medically require treatment with drugs that are not in line with the in- or exclusion criteria of this study or that are prohibited concomitant medications (see section 6.9) for this study
- •Bronchial asthma or chronic obstructive pulmonary disease (COPD) with forced expiratory volume in 1 second (FEV1) <60% of predicted
- •Restrictive lung disease with total lung capacity (TLC) <60% of predicted
- •Subjects on oxygen therapy
- •Severe congenital abnormalities of the lung, thorax, or diaphragm
- •Clinically relevant hepatic dysfunction shown by:
- •Aspartate aminotransferase (AST) ≥3 times the upper limit of normal (ULN) or
- •Child Pugh stage B and C in cirrhotic subjects
- •Severe renal impairment (glomerular filtration rate [GFR] <30mL/min/1.73 m2 calculated by the Modification of Diet in Renal Disease [MDRD] formula)
- •Uncontrolled arterial hypertension (SBP >180 mmHg or diastolic blood pressure [DBP] >110 mmHg)
- •SBP <110 mmHg at baseline
- •Myocardial disease, such as ischemic or dilative infiltrative myocardial disease (i.e. amyloidosis, hypertrophic cardiomyopathy)
- •Severe aortic or mitral stenosis, or any such stenosis with indication for surgery
- •Coronary artery disease with angina of Canadian Cardiovascular Society (CCS) class III or IV or requiring nitrates, unstable angina, or acute myocardial infarction <90 days before randomization
- •Reperfusion procedure (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) <90 days before randomization, or <21 days in case of a negative stress test effect after PCI
- •Stroke with persistent neurological deficit
- •Subjects positive for human immunodeficiency virus (HIV)
- •Resting HR while awake of <50 beats per minute (BPM) or >105 BPM (in case of atrial fibrillation >110 BPM)
- •Participation in another clinical study <90 days before randomization
- •Subjects with a medical disorder, condition, or history thereof that in the opinion of the investigator would impair the subject's ability to participate or complete the 26-week study
- •Subjects with underlying medical disorders with an anticipated life expectancy below 2 years because of a non-cardiac disease (e.g. active cancer disease with localized and / or metastasized tumor mass)
- •Subjects with a history of multiple drug allergies
- •Subjects with hypersensitivity to the investigational drug or any of the excipients
- •Previous assignment to treatment during this study
研究组 & 干预措施
Riociguat
Experimental
Riociguat up-titrated to a maximum of 1.5mg TID
干预措施: Riociguat (Drug)
Placebo
Placebo Comparator
Placebo sham-titrated TID
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline of cardiac output at rest, measured by right heart catheterization
时间窗: Baseline and 26 weeks after study drug treatment
Change from baseline of cardiac output at rest, measured by right heart catheterization after 26 weeks of study drug treatment
次要结局
- Change from baseline in cardiac magnetic resonance imaging parameters(Baseline and 26 weeks after study drug treatment)
- Change from baseline in hemodynamic parameters other than cardiac output(Baseline and 26 weeks after study drug treatment)
- Change from baseline in WHO functional class(Baseline and 26 weeks after study drug treatment)
- Change from baseline in biomarker levels(Baseline and 26 weeks after study drug treatment)
研究者
DBonderman
Assoc.Prof.Priv.Doz.Dr.
Medical University of Vienna
研究点 (1)
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