Beta-blockers for Oesophageal Varices

NCT03776955 | Unknown Phase 4 DMC

• 1 other identifier: 125861
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 4

Brief Summary

To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices

Conditions

Cirrhoses, Liver; Oesophageal Varices

Outcome Measures

Primary Outcomes (2)

• Variceal bleeding

  Time to first variceal haemorrhage

  3 years

• Health Economic assessment

  Assess the cost effectiveness of early intervention with non specific beta blockers in this patient population.

  3 years

Secondary Outcomes (8)

• Variceal bleed rate

  1 and 3 years

• Variceal bleeding needing intervention

  3 years

• Composite of variceal bleed rate and bleeding needing intervention

  3 years

• Clinical decompensation

  3 years

• Child Pugh Score for Cirrhosis mortality

  3 years

Study Arms (2)

Oral Carvedilol

EXPERIMENTAL

6.25 mg or 12.5 mg if tolerated

Drug: Carvedilol

Oral Placebo

PLACEBO COMPARATOR

Drug: Carvedilol

Interventions

Carvedilol DRUG

Oral tablet

Oral Carvedilol; Oral Placebo

Eligibility Criteria

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

You may qualify if:

• Age \>18 years
• Cirrhosis and portal hypertension, defined by any 2 of the following:
• A) Characteristic clinical examination findings; one or more of i) liver function tests ii) haematological panel iii) coagulation profile abnormalities B) Characteristic radiological findings; one or more of i) heterogeneous, small liver with irregular contour ii) splenomegaly iii) ascites iv) varices v) recanalized umbilical vein C) Fibrosis score \> stage 4 on liver biopsy D) FibroScan liver stiffness measurement \>15 kilo Pascal without other explanation
• Small oesophageal varices diagnosed within the last 3 months,- defined as \<5 mm in diameter or varices which completely disappear on moderate insufflation at gastroscopy.
• Not received a beta-blocker in the last week
• Capacity to provide informed consent

You may not qualify if:

• Non-cirrhotic portal hypertension
• Medium/large oesophageal varices (current or history of), defined as \>5 mm in diameter
• Isolated gastric, duodenal, rectal varices with or without evidence of recent bleeding
• Previous variceal haemorrhage
• Red signs accompanying varices at endoscopy
• Known intolerance to beta blockers
• Contraindication to beta blocker use i) Heart rate \<50 bpm ii) Known 2nd degree or higher heart block iii) Sick sinus syndrome iv) Systolic blood pressure \<85 mm Hg v) Chronic airways obstruction (asthma/COPD) vi) Floppy Iris Syndrome vii) CYP2D6 Poor Metaboliser viii) History of cardiogenic shock ix) History of severe hypersensitivity reaction to beta-blockers x) Untreated phaeochromocytoma xi) Severe peripheral vascular disease xii) Prinzmetal angina xiii) New York Heart Association IV heart failure
• Unable to provide informed consent
• Child Pugh C cirrhosis
• Already receiving a beta-blocker for another reason that cannot be discontinued
• Graft cirrhosis post liver transplantation
• Evidence of active malignancy without curative therapy planned
• Pregnant or lactating women
• Women of child bearing potential not willing to use adequate contraception during the protocol of IMP dosing
• Patients who have been on a CTIMP within the previous 3 months

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead
• King's College London: collaborator
• Guy's and St Thomas' NHS Foundation Trust: collaborator
• St George's University Hospitals NHS Foundation Trust: collaborator
• Cardiff University: collaborator
• Brighton and Sussex University Hospitals NHS Trust: collaborator

Study Sites (4)

Royal Victoria Hospital

Belfast, Northern Ireland, BT12 6BA, United Kingdom

NOT YET RECRUITING

Queen Elizabeth Hospital

Birmingham, B15 2TT, United Kingdom

NOT YET RECRUITING

Royal London Hospital (Barts)

London, E1 1FR, United Kingdom

NOT YET RECRUITING

King's College Hosptial NHS Foundation Trust (Denmark Hill)

London, United Kingdom

RECRUITING

MeSH Terms

Conditions

Esophageal and Gastric Varices

Interventions

Carvedilol

Condition Hierarchy (Ancestors)

Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases; Hypertension, Portal; Liver Diseases

Intervention Hierarchy (Ancestors)

Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 3-Ring

Study Officials

• Mark McPhail, BSc, PhD, MB ChB

  King's College Hospital NHS Trust

  STUDY DIRECTOR

• Ben Carter, BSc, PhD

  King's College London

  STUDY DIRECTOR

Central Study Contacts

Vishal Patel, BSc, MBBS, MRCP, MPhil

CONTACT

+44 (0)20 3299 3654; vishal.patel@nhs.net

Kieran Brack, BSc, PhD

CONTACT

+44 (0)20 3299 7142; kch-tr.boppptrial@nhs.net

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Placebo matched control
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 30, 2018
• First Posted: December 17, 2018
• Study Start: June 17, 2019
• Primary Completion: September 1, 2024
• Study Completion: December 1, 2024
• Last Updated: October 3, 2019

Record last verified: 2019-10

Locations

GB (4)