Clinical trial NCT01640964: An Exploratory Haemodynamic Study in Patients With Compensated Cirrhosis and Portal Hypertension
Official title: An Exploratory Study to Investigate the Haemodynamic Effects of Serelaxin (RLX030) in Patients With Compensated Cirrhosis and Portal Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Compensated Cirrhosis and Portal Hypertension
Keywords: Portal hypertension, cirrhosis, TIPSS, MRI, MRA, portal pressure, portal pressure gradient
Lead sponsor: Novartis
Sponsor class: INDUSTRY
First posted: 2012-07-16
Enrollment: 47
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).


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

Primary outcomes:
measure: Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Serelaxin Treatment Group Only))
timeFrame: Baseline, 120 min post serelaxin infusion
measure: Change From Baseline of the Portal Pressure Gradient (PPG) (Study Part B)
timeFrame: Baseline, 120 min post-infusion start
Secondary outcomes:
measure: Change From Baseline of the Blood Flow for the Total Renal Arteries (Study Part A (Terlipressin Acetate Group Only))
timeFrame: Baseline, 120 min post infusion
measure: Change From Baseline of the Blood Flow for the Hepatic Artery (Study Part A (Serelaxin Treatment Group Only))
timeFrame: Baseline, 120 min post-infusion
measure: Change From Baseline of the Blood Flow for the Superior Mesenteric Artery (Study Part A (Serelaxin Treatment Group Only))
timeFrame: Baseline, 120 min post-infusion
measure: Change From Baseline of the Blood Flow for the Descending Thoracic Aorta (Study Part A (Serelaxin Treatment Group Only))
timeFrame: Baseline, 120 min post-infusion
measure: Change From Baseline of the Blood Flow for the Portal Vein (Study Part A (Serelaxin Treatment Group Only))
timeFrame: Baseline, 120 min post-infusion
measure: Change From Baseline of the Portal Vein Pressure (PVP) (Study Part B)
timeFrame: Baseline, 120 min post infusion
measure: Number of Patients With Total Adverse Events, Serious Adverse and Death as Assessment of Safety and Tolerability of Serelaxin
timeFrame: 4 weeks
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: Novartis Investigative Site
Study officials:
affiliation: Novartis Pharmaceuticals
name: Novartis Pharmaceuticals
role: STUDY_DIRECTOR
References:
citation: 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.