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

NCT ID: NCT01640964

Last Updated: 2016-03-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 47 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-04-30
• Study Completion Date: 2014-12-31

Brief Summary

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).

Conditions

Compensated Cirrhosis and Portal Hypertension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Part A: Terlipressin acetate

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

Group Type: EXPERIMENTAL

Terlipressin acetate

Intervention Type: DRUG

IV bolus injection

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

Group Type: EXPERIMENTAL

Serelaxin (RLX030)

Intervention Type: 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

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.

Group Type: EXPERIMENTAL

Serelaxin (RLX030)

Intervention Type: 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

Interventions

Terlipressin acetate

IV bolus injection

Intervention Type: DRUG

Serelaxin (RLX030)

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Novartis Pharmaceuticals

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Novartis Pharmaceuticals

Role: STUDY_DIRECTOR

Novartis Pharmaceuticals

Locations

Novartis Investigative Site

Edinburgh, , United Kingdom

Countries

United Kingdom

References

Snowdon VK, Lachlan NJ, Hoy AM, Hadoke PW, Semple SI, Patel D, Mungall W, Kendall TJ, Thomson A, Lennen RJ, Jansen MA, Moran CM, Pellicoro A, Ramachandran P, Shaw I, Aucott RL, Severin T, Saini R, Pak J, Yates D, Dongre N, Duffield JS, Webb DJ, Iredale JP, Hayes PC, Fallowfield JA. Serelaxin as a potential treatment for renal dysfunction in cirrhosis: Preclinical evaluation and results of a randomized phase 2 trial. PLoS Med. 2017 Feb 28;14(2):e1002248. doi: 10.1371/journal.pmed.1002248. eCollection 2017 Feb.

Reference Type: DERIVED

PMID: 28245243 (View on PubMed)

Other Identifiers

2012-000236-26

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CRLX030X2201

Identifier Type: -

Identifier Source: org_study_id