Beta-blockers for Oesophageal Varices

NCT ID: NCT03776955

Last Updated: 2019-10-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE4

Total Enrollment

1200 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-06-17

Study Completion Date

2024-12-31

Brief Summary

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

Detailed Description

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Cirrhosis or liver scarring is an important problem in healthcare in the United Kingdom. 60,000 patients are living with this disease and about 11,000 people every year will die because of it. There are several ways in which patients with this severe form of liver disease become unwell or die and bleeding from the oesophagus or stomach is one. Cirrhosis causes pressure changes inside the abdomen and swelling of veins in the oesophagus (called "varices") which can bleed catastrophically.

The investigators know that when varices are large, treatment can be initiated with medication called beta-blockers to reduce the pressure in the varices. If the varices are small, the medical community is not sure if treatment with beta-blockers will work. This study aims to address this uncertainty.

Patients who are recruited to the study with small varices will be randomised to either beta-blockers or a placebo. Research sites will observe patients closely for 3 years for bleeding from their varices or other complications of cirrhosis or side effects of taking medication. This is the amount of time needed to observe for bleeding when the varices are small. Research sites will review the patients every 6 months including assessing the varices by a camera test called an endoscopy at the beginning and each year until the study is finished.

During the study, patients will be involved with the conduct and management of the research. Patient will also be notified on the trial results at the end of the study. The barriers and facilitators in adjusting the dose of the tablets to optimise treatment effects primary care will be along with patients' views on taking part in the trial, and whether the side effects justify the potential benefits of reducing the risk of bleeding. The investigators estimate this risk could be reduced from 20% of patients having significant bleeding to 10% over 3 years.

The investigators will measure the impact of beta-blockers on the overall costs to the National Health Service (NHS) of caring for people with cirrhosis during the trial, and will also assess the impact of treatment on both mortality and quality of life using a combined measure, the Quality Adjusted Life-Year (QALY). The investigators will use a mathematical prediction model to estimate the impact of treatment on costs, mortality and quality of life over a patient's lifetime and will assess whether any increased costs are justified by better outcomes for patients and represent good value for money for the NHS budget.

Finally, the results of the study will be published in the medical literature and discuss the findings at medical conferences, patient groups and with charities involved in helping patients with cirrhosis such as the British Liver Trust.

Conditions

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Cirrhoses, Liver Oesophageal Varices

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors
Placebo matched control

Study Groups

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Oral Carvedilol

6.25 mg or 12.5 mg if tolerated

Group Type EXPERIMENTAL

Carvedilol

Intervention Type DRUG

Oral tablet

Oral Placebo

Group Type PLACEBO_COMPARATOR

Carvedilol

Intervention Type DRUG

Oral tablet

Interventions

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Carvedilol

Oral tablet

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Age \>18 years
2. 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
3. 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.
4. Not received a beta-blocker in the last week
5. Capacity to provide informed consent

Exclusion Criteria

1. Non-cirrhotic portal hypertension
2. Medium/large oesophageal varices (current or history of), defined as \>5 mm in diameter
3. Isolated gastric, duodenal, rectal varices with or without evidence of recent bleeding
4. Previous variceal haemorrhage
5. Red signs accompanying varices at endoscopy
6. Known intolerance to beta blockers
7. 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
8. Unable to provide informed consent
9. Child Pugh C cirrhosis
10. Already receiving a beta-blocker for another reason that cannot be discontinued
11. Graft cirrhosis post liver transplantation
12. Evidence of active malignancy without curative therapy planned
13. Pregnant or lactating women
14. Women of child bearing potential not willing to use adequate contraception during the protocol of IMP dosing
15. Patients who have been on a CTIMP within the previous 3 months
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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King's College London

OTHER

Sponsor Role collaborator

Guy's and St Thomas' NHS Foundation Trust

OTHER

Sponsor Role collaborator

St George's University Hospitals NHS Foundation Trust

OTHER

Sponsor Role collaborator

Cardiff University

OTHER

Sponsor Role collaborator

Brighton and Sussex University Hospitals NHS Trust

OTHER

Sponsor Role collaborator

King's College Hospital NHS Trust

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Mark McPhail, BSc, PhD, MB ChB

Role: STUDY_DIRECTOR

King's College Hospital NHS Trust

Ben Carter, BSc, PhD

Role: STUDY_DIRECTOR

King's College London

Locations

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Royal Victoria Hospital

Belfast, Northern Ireland, United Kingdom

Site Status NOT_YET_RECRUITING

Queen Elizabeth Hospital

Birmingham, , United Kingdom

Site Status NOT_YET_RECRUITING

Royal London Hospital (Barts)

London, , United Kingdom

Site Status NOT_YET_RECRUITING

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

London, , United Kingdom

Site Status RECRUITING

Countries

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United Kingdom

Central Contacts

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Vishal Patel, BSc, MBBS, MRCP, MPhil

Role: CONTACT

+44 (0)20 3299 3654

Kieran Brack, BSc, PhD

Role: CONTACT

+44 (0)20 3299 7142

Facility Contacts

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Angela Toner

Role: primary

028 90633197

Emma Burke

Role: primary

0121 3718451

Role: backup

07770 827573

James Hand

Role: primary

020 3594 6773

Ruhuma Uddin, BSc

Role: primary

020 3299 7142

Other Identifiers

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125861

Identifier Type: -

Identifier Source: org_study_id

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