An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension

Study Overview
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Brief Summary
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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).

Official Title
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An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension

Conditions
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Compensated Cirrhosis and Portal Hypertension

Intervention / Treatment
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* Drug: Terlipressin acetate
* Drug: Serelaxin (RLX030)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Study Parts A and B: -Cirrhosis of alcohol aetiology according to physician's assessment prior to screening. Part A: -Cirrhosis with clinical and/or endoscopic evidence of portal hypertension (e.g. oesophageal varices). Part B: Cirrhosis with TIPSS in situ and PPG>5mmHg. Fully functioning TIPSS without variceal filling as confirmed by portography. Exclusion Criteria: 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 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. Part A: BMI (weight[kg] / height[m^2]) > 40 kg/m^2. Any contraindication to having an MRI scan Part B: -Contraindication to catheterization

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part A: Terlipressin acetate<br>Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection. | Drug: Terlipressin acetate<br>* IV bolus injection<br>|
| Experimental: Part A: Serelaxin (RLX030)<br>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 | Drug: Serelaxin (RLX030)<br>* Part A2: IV infusion for 2-3 hours; duration of infusion depends on time required for completion of MRA data acquisition; Part B: IV infusion for approximately 2 hours<br>|
| Experimental: Part B Serelaxin (RLX030)<br>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. | Drug: Serelaxin (RLX030)<br>* Part A2: IV infusion for 2-3 hours; duration of infusion depends on time required for completion of MRA data acquisition; Part B: IV infusion for approximately 2 hours<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only)) | 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) | Baseline, 120 min post serelaxin infusion | 
| Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B) | 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). | Baseline, 120 min post-infusion start | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only)) | 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) | Baseline, 120 min post infusion | 
| Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only)) | A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as hepatic artery. The flow is the average flow over the cardiac cycle. Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment). | Baseline, 120 min post-infusion | 
| Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only)) | A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as superior mesenteric artery. The flow is the average flow over the cardiac cycle. Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment). | Baseline, 120 min post-infusion | 
| Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only)) | A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as descending thoracic aorta. The flow is the average flow over the cardiac cycle. Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment). | Baseline, 120 min post-infusion | 
| Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only)) | A non-contrast magnetic resonance angiography (MRA) sequence was performed to acquire phase contrast blood flow measurements from vessels of interest such as the portal vein. The flow is the average flow over the cardiac cycle. Baseline blood flow measurements are measured at pre-dose (Day 1, 0 min post-treatment). | Baseline, 120 min post-infusion | 
| Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B) | Portal vein pressure 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). | Baseline, 120 min post infusion | 
| Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin | This endpoint reports patients with any adverse event, serious adverse event and death for the serelaxin group of Part A and Part B of the study. | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient