Serelaxin To Lower Portal Pressure

NCT02669875 | Completed Phase 2

• 1 other identifier: STOPP
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Portal hypertension (an increase in blood pressure in the portal vein that carries the blood from the intestine and spleen to the liver) underlies most of the serious complications of liver cirrhosis. This randomised placebo controlled study in people with liver cirrhosis evaluates the acute effects serelaxin (RLX030) infusion on portal hypertension and liver blood flow.

Conditions

Liver Cirrhosis; Hypertension, Portal

Outcome Measures

Primary Outcomes (1)

• Change from baseline in fasting hepatic venous pressure gradient (HVPG)

  Baseline, after 2 hours

Secondary Outcomes (8)

• Change from baseline in fasting hepatic venous pressure gradient (HVPG)

  Baseline, after 1 hour

• Change from baseline in fasting hepatic blood flow

  Baseline, after 2 hours

• Change from baseline in inferior vena cava pressure

  Baseline, after 2 hours

• Change from baseline in cardiac index

  Baseline, after 2 hours

• Change from baseline in systemic vascular resistance index

  Baseline, after 2 hours

Study Arms (2)

Serelaxin

ACTIVE COMPARATOR

IV infusion of serelaxin (RLX030) for 2 hours

Drug: Serelaxin

Placebo

PLACEBO COMPARATOR

IV infusion of placebo (20mM sodium acetate pH5) matched to serelaxin for 2 hours

Drug: Placebo

Interventions

Serelaxin DRUG

Serelaxin solution diluted in 5% glucose volume/volume (v/v) solution

Also known as: RLX030, Recombinant human relaxin-2

Serelaxin

Placebo DRUG

Placebo solution (20mM sodium acetate pH5) diluted in 5% v/v glucose solution

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female adult subjects over 18 years of age
• Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
• Clinical imaging-diagnosed or biopsy-proven liver cirrhosis of any aetiology
• Evidence of portal hypertension either on imaging or previous endoscopy
• Patients with large/grade 3 varices as identified by endoscopy within 6 months of screening must be in an endoscopic band ligation programme at the time of study entry
• Suspected hepatic venous pressure gradient (HVPG) ≥10 mmHg at baseline

You may not qualify if:

• Pregnancy or breast feeding
• Women of child-bearing potential not using highly effective methods of contraception
• Severe liver failure defined by one of the following: Prothrombin activity \<40%, Bilirubin \>5 mg/dL (85umol/L), hepatic encephalopathy \> grade I
• A history of variceal bleed within 1 month prior to 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
• Hepatocellular carcinoma or history of malignancy of any organ system (other than localized basal cell carcinoma of the skin) treated or untreated
• Portal vein thrombosis
• Previous surgical shunt or TIPSS
• Current use of beta-blockers or nitrates, any other drug therapy known to have an influence on portal pressure (diuretics permitted provided patients have been on a stable dose for at least 30 days)
• History of drug or alcohol abuse within 1 month of enrolment
• Sitting Systolic Blood Pressure \<110 mmHg at screening visit or within 10 minutes prior to starting study drug infusion
• Use of other investigational drugs within 5 half-lives of enrolment, or within 30 days/until the expected pharmacodynamic effect has returned to baseline, whichever is longer
• Significant arrhythmias, which include any of the following: sustained ventricular tachycardia, bradycardia with sustained ventricular rate \< 45 beats per minute or atrial fibrillation/flutter with sustained ventricular response of \> 90 beats per minute at rest, or Long QT syndrome or corrected QT interval (QTc) \> 450 msec (QT correction will be performed using the Fridericia correction method: QTcF = QT/RR0.33) for males and \> 460 msec for females at screening visit
• Documented hypersensitivity to intravenous contrast agents and/or iodine
• Severe renal impairment (eGFR\<30mL/min /1.73m2)

Sponsors & Collaborators

• University of Edinburgh: lead
• Novartis Pharmaceuticals: collaborator
• NHS Lothian: collaborator

Study Sites (1)

Liver Unit, Royal Infirmary of Edinburgh

Edinburgh, EH164TJ, United Kingdom

Location

Related Publications (3)

• Fallowfield JA, Hayden AL, Snowdon VK, Aucott RL, Stutchfield BM, Mole DJ, Pellicoro A, Gordon-Walker TT, Henke A, Schrader J, Trivedi PJ, Princivalle M, Forbes SJ, Collins JE, Iredale JP. Relaxin modulates human and rat hepatic myofibroblast function and ameliorates portal hypertension in vivo. Hepatology. 2014 Apr;59(4):1492-504. doi: 10.1002/hep.26627. Epub 2014 Mar 3.

  PMID: 23873655 BACKGROUND

• Kobalava Z, Villevalde S, Kotovskaya Y, Hinrichsen H, Petersen-Sylla M, Zaehringer A, Pang Y, Rajman I, Canadi J, Dahlke M, Lloyd P, Halabi A. Pharmacokinetics of serelaxin in patients with hepatic impairment: a single-dose, open-label, parallel group study. Br J Clin Pharmacol. 2015 Jun;79(6):937-45. doi: 10.1111/bcp.12572.

  PMID: 25511105 BACKGROUND

• Gifford FJ, Dunne PDJ, Weir G, Ireland H, Graham C, Tuck S, Hayes PC, Fallowfield JA. A phase 2 randomised controlled trial of serelaxin to lower portal pressure in cirrhosis (STOPP). Trials. 2020 Mar 12;21(1):260. doi: 10.1186/s13063-020-4203-9.

  PMID: 32164767 DERIVED

MeSH Terms

Conditions

Liver Cirrhosis; Hypertension, Portal

Interventions

serelaxin protein, human

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2016
• First Posted: February 1, 2016
• Study Start: October 18, 2017
• Primary Completion: August 31, 2018
• Study Completion: August 31, 2018
• Last Updated: October 11, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)