Comparing Carvedilol versus Placebo on the rate of variceal haemorrhage in patients with cirrhosis of the liver and small oesophageal varices

Phase 1

• Conditions: iver cirrhosis with small oesophageal varices; MedDRA version: 20.0Level: LLTClassification code 10024667Term: Liver cirrhosisSystem Organ Class: 100000004871; MedDRA version: 21.1Level: LLTClassification code 10055489Term: Esophageal varices in cirrhosis of liverSystem Organ Class: 100000004856; Therapeutic area: Body processes [G] - Digestive System and Oral Physiological Phenomena [G10]

• Registration Number: EUCTR2018-002509-78-GB
• Lead Sponsor: Kings College Hospital NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2019-01-24
• Last Update Posted: 18 March 2020

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 1200

Inclusion Criteria

o Age 18 years and over

o Cirrhosis and portal hypertension, defined by any 2 of the following:
1) Characteristic clinical examination findings; one or more of:
Characteristic liver function tests
•Haematological panel
•Coagulation profile abnormalities
2)Characteristic radiological findings; one or more of
•Heterogeneous liver with irregular contour
•splenomegaly
•ascites
•varices
•recanalized umbilical vein
3) FibroScan liver stiffness measurement >15 kPa without other explanation
4) Fibrosis score > stage 4 on liver biopsy (presence of a relevant fibrosis score by biopsy does not require additional clinical examination / radiological / FibroScan supporting evidence)

oSmall oesophageal varices diagnosed within the last 6 months, defined as =5 mm in diameter or varices which completely disappear on moderate insufflation at gastroscopy.

oNot received a beta-blocker in the last week

oCapacity to provide informed consent

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 1200

Exclusion Criteria

o Non-cirrhotic portal hypertension
o Medium/large oesophageal varices (current or history [decreasing in size without curative therapy), defined as >5 mm in diameter
o Gastric (IGV and GOV2), duodenal, rectal varices with or without evidence of recent bleeding. For gastric varices, this includes:
? IGV-1 and IGV-2 (isolated gastric varices)
? GOV2 (gastric varices continuing into the cardia)
? Note GOV1 (gastric varices continuing into the lesser curve) are not an exclusion if present with small oesophageal varices
o Previous variceal haemorrhage
o Previous band ligation or glue injection of oesophageal and/or gastric varices
o Red signs accompanying varices at endoscopy
o Known intolerance to beta blockers
o Contraindications to beta blocker use:
• Heart rate <50 bpm
• Known 2nd degree or higher heart block
• Sick sinus syndrome
• Systolic blood pressure <85 mmHg
• Chronic airways obstruction (asthma/COPD)
• Floppy Iris Syndrome
• CYP2D6 Poor Metaboliser
• History of cardiogenic shock
• History of severe hypersensitivity reaction to beta-blockers
• Untreated phaeochromocytoma
• Severe peripheral vascular disease
• Prinzmetal angina
• NYHA IV heart failure
o Unable to provide informed consent
o Child Pugh C cirrhosis
o Already receiving a beta-blocker for another reason that cannot be discontinued
o Graft cirrhosis post liver transplantation
o Evidence of active malignancy without curative therapy planned
o Pregnant or lactating women
o Women of child bearing potential not willing to use adequate contraception during the period of IMP dosing (1 week washout period)
o Patients who have been on a CTIMP within the previous 3 months

Study & Design

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