A study to investigate whether Serelaxin reduces high blood pressure in the portal vein in people with liver cirrhosis

Phase 1

• Conditions: Portal hypertension in patients with liver cirrhosis.; MedDRA version: 20.1Level: PTClassification code 10036200Term: Portal hypertensionSystem Organ Class: 10019805 - Hepatobiliary disorders; Therapeutic area: Diseases [C] - Digestive System Diseases [C06]

• Registration Number: EUCTR2015-004031-12-GB
• Lead Sponsor: niversity of Edinburgh

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2018-05-23
• Study Completion: 2018-08-31
• Last Update Posted: 3 August 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 15

Inclusion Criteria

1) Male or female adult subjects over 18 years of age
2) Able to provide written informed consent and able to understand and willing to comply with the requirements of the study
3) Clinical/imaging-diagnosed or biopsy-proven liver cirrhosis of any aetiology
4) Evidence of portal hypertension either on imaging or previous endoscopy
5) 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
6) Suspected hepatic venous pressure gradient (HVPG) =10 mmHg at baseline
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5

Exclusion Criteria

1) Pregnancy or nursing (lactating) women
2) Women of child-bearing potential not using highly effective methods of contraception.

•Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective methods of contraception during the entire period of the study – until 4 weeks following Visit 2.

•Further details are found at the following web address: (http://www.hma.eu/fileadmin/dateien/Human_Medicines/01- About_HMA/Working_Groups/CTFG/2014_09_HMA_CTFG_Contraception.pdf

•In case of use of oral contraception women should have been stable on the same pill for a minimum of 3 months before taking the investigational drug.

•Contraception must be continued for up to the end of study – 4 weeks following Visit 2.

3) Severe liver failure defined by one of the following: Prothrombin activity < 40%, Bilirubin > 5 mg/dL (85umol/L), hepatic encephalopathy > grade I
4) Presence of any non-controlled and clinically significant disease that could affect the study outcome or that would place the patient at undue risk
5) A history of variceal bleed within 1 month prior to visit 1
6) Hepatocellular carcinoma or history of malignancy of any organ system (other than localized basal cell carcinoma of the skin) treated or untreated.
7) Portal vein thrombosis
8) Previous surgical shunt or TIPSS
9) 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)
10) History of drug or alcohol abuse within 1 month of enrolment
11) Sitting Systolic Blood Pressure <110 mmHg at screening visit or within 10 minutes prior to starting study drug infusion
12) 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
13) 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 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 1)
14) Documented hypersensitivity to intravenous contrast agents and/or iodine
15) Severe renal impairment (eGFR<30mL/min /1.73m2)
16) Significant left ventricular outflow tract obstructions (e.g., severe valvular aortic stenosis, obstructive cardiomyopathy), severe mitral stenosis, restrictive amyloid myocardiopathy, acute myocarditis
17) Severe aortic insufficiency or severe mitral regurgitation for which surgical or percutaneous intervention is indicated
18) Major neurologic event including cerebrovascular events, within 30 days prior to screening
19) Clinical evidence of acute coronary syndrome currently or within 30 days prior to enrolment
20) History of hypersensitivity to study drug serelaxin or study drug ingredients
21) Inability to follow instructions or comply with follow-up procedures
22) Permanent pacemaker, cardiac resynchronisation device or implantable cardioverter-defibrillator in situ

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To demonstrate that 2 hours treatment with serelaxin through a drip reduces the portal pressure in patients with liver cirrhosis and high blood pressure in the portal vein.;Secondary Objective: To determine the effect of serelaxin treatment on liver blood flow. <br>To determine the effect of serelaxin treatment on the general circulation. <br>To collect further information on the safety and tolerability of serelaxin in people with liver cirrhosis.<br>;Primary end point(s): Change from baseline in fasting hepatic venous pressure gradient (HVPG) after 2 hours serelaxin infusion. ;Timepoint(s) of evaluation of this end point: Baseline, 1 hour and 2 hours after initiation of serelaxin infusion.