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

Novartis Pharmaceuticals47 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Compensated Cirrhosis and Portal Hypertension

Interventions

Terlipressin acetateDRUG

IV bolus injection

Serelaxin (RLX030)DRUG

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

Eligibility

Sex: ALLMin age: 18 YearsMax age: 75 Years

Medical Language ↔ Plain English

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

Locations (1)

Novartis Investigative Site

Edinburgh, United Kingdom

Outcomes

Primary Outcomes

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)

Time frame: 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).

Time frame: Baseline, 120 min post-infusion start

Secondary Outcomes

Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))

Time frame: 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).

Time frame: Baseline, 120 min post-infusion

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.