NCT02669875已完成2 期
Serelaxin To Lower Portal Pressure in Patients With Cirrhosis and Portal Hypertension
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
- 15
- 试验地点
- 1
- 主要终点
- Change from baseline in fasting hepatic venous pressure gradient (HVPG)
研究概览
简要总结
Portal hypertension (an increase in blood pressure in the portal vein that carries the blood from the intestine and spleen to the liver) underlies most of the serious complications of liver cirrhosis. This randomised placebo controlled study in people with liver cirrhosis evaluates the acute effects serelaxin (RLX030) infusion on portal hypertension and liver blood flow.
详细描述
This study will investigate the effects of the investigational drug serelaxin (a recombinant form of the peptide human relaxin-2) on portal hypertension in patients with liver cirrhosis. The investigators will measure portal pressure by hepatic venous pressure gradient (HVPG) and hepatic blood flow by indocyanine green (ICG) clearance to evaluate the potential benefits of the drug. In a recently completed small exploratory open-label phase 2 study (EudraCT no. 201200023626, NCT01640964), Part B demonstrated that serelaxin can lower portal pressure.
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
- •Male or female adult subjects over 18 years of age
- •Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
- •Clinical imaging-diagnosed or biopsy-proven liver cirrhosis of any aetiology
- •Evidence of portal hypertension either on imaging or previous endoscopy
- •Patients with large/grade 3 varices as identified by endoscopy within 6 months of screening must be in an endoscopic band ligation programme at the time of study entry
- •Suspected hepatic venous pressure gradient (HVPG) ≥10 mmHg at baseline
排除标准
- •Pregnancy or breast feeding
- •Women of child-bearing potential not using highly effective methods of contraception
- •Severe liver failure defined by one of the following: Prothrombin activity <40%, Bilirubin >5 mg/dL (85umol/L), hepatic encephalopathy > grade I
- •A history of variceal bleed within 1 month prior to visit 1
- •Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk
- •Hepatocellular carcinoma or history of malignancy of any organ system (other than localized basal cell carcinoma of the skin) treated or untreated
- •Portal vein thrombosis
- •Previous surgical shunt or TIPSS
- •Current use of beta-blockers or nitrates, any other drug therapy known to have an influence on portal pressure (diuretics permitted provided patients have been on a stable dose for at least 30 days)
- •History of drug or alcohol abuse within 1 month of enrolment
- •Sitting Systolic Blood Pressure <110 mmHg at screening visit or within 10 minutes prior to starting study drug infusion
- •Use of other investigational drugs within 5 half-lives of enrolment, or within 30 days/until the expected pharmacodynamic effect has returned to baseline, whichever is longer
- •Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate < 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of > 90 beats per minute at rest, or Long QT syndrome or corrected QT interval (QTc) > 450 msec (QT correction will be performed using the Fridericia correction method: QTcF = QT/RR0.33) for males and > 460 msec for females at screening visit
- •Documented hypersensitivity to intravenous contrast agents and/or iodine
- •Severe renal impairment (eGFR<30mL/min /1.73m2)
- •Significant left ventricular outflow tract obstructions (e.g., severe valvular aortic stenosis, obstructive cardiomyopathy), severe mitral stenosis, restrictive amyloid myocardiopathy, acute myocarditis
- •Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated
- •Major neurologic event including cerebrovascular events, within 30 days prior to screening
- •Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrolment
- •History of hypersensitivity to study drug serelaxin or study drug ingredients
- •Inability to follow instructions or comply with follow-up procedures.
- •Permanent pacemaker, cardiac resynchronisation device or implantable cardioverter-defibrillator in situ
研究组 & 干预措施
Serelaxin
Active Comparator
IV infusion of serelaxin (RLX030) for 2 hours
干预措施: Serelaxin (Drug)
Placebo
Placebo Comparator
IV infusion of placebo (20mM sodium acetate pH5) matched to serelaxin for 2 hours
干预措施: Placebo (Drug)
结局指标
主要结局
Change from baseline in fasting hepatic venous pressure gradient (HVPG)
时间窗: Baseline, after 2 hours
次要结局
- Change from baseline in systemic vascular resistance index(Baseline, after 2 hours)
- Number of participants with adverse events(4 weeks)
- Change from baseline in blood biomarker measurements(Baseline, after 2 hours)
- Change from baseline in fasting hepatic venous pressure gradient (HVPG)(Baseline, after 1 hour)
- Change from baseline in fasting hepatic blood flow(Baseline, after 2 hours)
- Change from baseline in inferior vena cava pressure(Baseline, after 2 hours)
- Change from baseline in cardiac index(Baseline, after 2 hours)
- Change from baseline in aortic pulse wave velocity(Baseline, after 2 hours)
研究者
研究点 (1)
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