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

Novartis

Status and phase: Completed; Phase 2

Conditions: Compensated Cirrhosis and Portal Hypertension

Treatments: Drug: Terlipressin acetate; Drug: Serelaxin (RLX030)

Study type: Interventional

Funder types: Industry

Identifiers

NCT01640964

CRLX030X2201

2012-000236-26 (EudraCT Number)

Details and patient eligibility

About

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).

Enrollment: 47 patients

Sex: All

Ages: 18 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

47 participants in 3 patient groups

Part A: Terlipressin acetate

Experimental group

Description:

Patients received terlipressin acetate 2 mg intravenous (IV) bolus injection.

Treatment:

Drug: Terlipressin acetate

Part A: Serelaxin (RLX030)

Experimental group

Description:

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

Treatment:

Drug: Serelaxin (RLX030)

Part B Serelaxin (RLX030)

Experimental group

Description:

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.

Treatment:

Drug: Serelaxin (RLX030)