An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 47
- 试验地点
- 1
- 主要终点
- Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
研究概览
简要总结
The main purpose of this exploratory study was to investigate the effect of serelaxin (RLX030) infusion on the hepatic and renal circulation in patients with compensated cirrhosis and portal hypertension. Measurements were acquired non-invasively using magnetic resonance angiography (MRA) (study part A) and more directly via cannulation of the hepatic portal vein during a routine transjugular intrahepatic portosystemic shunt (TIPSS) check procedure (study part B), to determine the acute haemodynamic response to serelaxin (RLX030).
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
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Study Parts A and B:
- •Cirrhosis of alcohol aetiology according to physician's assessment prior to screening.
- •Cirrhosis with clinical and/or endoscopic evidence of portal hypertension (e.g. oesophageal varices).
- •Cirrhosis with TIPSS in situ and PPG>5mmHg.
- •Fully functioning TIPSS without variceal filling as confirmed by portography.
排除标准
- •Study Parts A and B:
- •Use of any drug to treat portal hypertension (e.g. vasodilators such as non-selective beta blockers or nitrates) within 1 month prior to screening.
- •Decompensated cirrhosis (Child-Pugh score >9 points, and/or ascites requiring diuretics, and/or hepatic encephalopathy) at visit
- •Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk.
- •BMI (weight[kg] / height[m^2]) > 40 kg/m^
- •Any contraindication to having an MRI scan
- •Contraindication to catheterization
研究组 & 干预措施
Part A: Terlipressin acetate
Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.
干预措施: Terlipressin acetate (Drug)
Part A: Serelaxin (RLX030)
Randomized patients received an intravenous serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min.; duration of infusion depends on time required for completion of magnetic resonance angiography (MRA) data acquisition
干预措施: Serelaxin (RLX030) (Drug)
Part B Serelaxin (RLX030)
The patients enrolled in this part of the study received an intravenous (iv) serelaxin infusion at two different infusion rates: 80 μg/kg/day for 60 min followed by 30 μg/kg/day for at least 60 min; duration of infusion depends on time required for completion of Portal pressure gradient (PPG) data acquisition.
干预措施: Serelaxin (RLX030) (Drug)
结局指标
主要结局
Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
时间窗: Baseline, 120 min post serelaxin infusion
The flow is the average flow over the cardiac cycle. Total renal artery flow = left renal artery flow + right renal artery flow. These measurements were collected through magnetic resonance angiography (MRA) scans. Baseline blood flow for total renal artery is measured at pre-dose (Day 1, 0 min post-treatment)
Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B)
时间窗: Baseline, 120 min post-infusion start
Direct venous pressure was measured by portal pressure gradient (PPG). PPG = portal vein pressure (PVP) - inferior vena cava pressure (IVCP). Baseline blood flow for PPG was measured at pre-dose (Day 1, 0 min post-treatment). PVP was measured at 15 min intervals (i.e. prior to and at 15, 30, 45, 60, 75, 90, 105, and 120 min of serelaxin infusion).
次要结局
- Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))(Baseline, 120 min post infusion)
- Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))(Baseline, 120 min post-infusion)
- Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))(Baseline, 120 min post-infusion)
- Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))(Baseline, 120 min post-infusion)
- Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin(4 weeks)
- Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))(Baseline, 120 min post-infusion)
- Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)(Baseline, 120 min post infusion)