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Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of Oesophageal Varices Trial. (BOPPP)

Primary Purpose

Cirrhosis, Liver, Portal Hypertension, Variceal Hemorrhage

Status
Recruiting
Phase
Phase 4
Locations
United Kingdom
Study Type
Interventional
Intervention
Carvedilol
Placebo
Sponsored by
King's College Hospital NHS Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Cirrhosis, Liver

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Age 18 years and over Cirrhosis and portal hypertension, Small oesophageal varices diagnosed within the last 6 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 Exclusion Criteria: Non-cirrhotic portal hypertension Medium/large oesophageal varices (current or history [decreasing in size without curative therapy]), defined as >5 mm in diameter Gastric (IGV and GOV2), duodenal, rectal varices with or without evidence of recent bleeding. Previous variceal haemorrhage Previous band ligation or glue injection of oesophageal and/or gastric varices Red signs accompanying varices at endoscopy Known intolerance to beta blockers Contraindications to beta blocker use 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 period of IMP dosing Patients who have been on a CTIMP within the previous 3 months Clinical symptoms consistent with COVID-19

Sites / Locations

  • King's College HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Carvedilol

Placebo

Arm Description

Oral Carvedilol 6.25 mg to 12.5 mg OD/ or 6.25mg BD (maximum dose 12.5mg)

Oral tablet (1 or 2 tablets)

Outcomes

Primary Outcome Measures

Variceal Haemorrhage

Secondary Outcome Measures

Full Information

First Posted
January 21, 2021
Last Updated
May 23, 2023
Sponsor
King's College Hospital NHS Trust
Collaborators
King's College London, Cardiff University, Brighton and Sussex University Hospitals NHS Trust
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1. Study Identification

Unique Protocol Identification Number
NCT05872698
Brief Title
Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of Oesophageal Varices Trial.
Acronym
BOPPP
Official Title
Beta-blockers Or Placebo for Primary Prophylaxis of Oesophageal Varices (BOPPP Trial). A Blinded, UK Multi-centre, Clinical Effectiveness and Cost-effectiveness Randomised Controlled Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 1, 2019 (Actual)
Primary Completion Date
December 2026 (Anticipated)
Study Completion Date
December 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
King's College Hospital NHS Trust
Collaborators
King's College London, Cardiff University, Brighton and Sussex University Hospitals NHS Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Research has proven that large varices can be treated with beta-blockers (a type of anti-hypertensive medication) to reduce the pressure in the veins. The management of small varices is still uncertain. This study aims to discover if beta blockers can be used in this setting. We hypothesize that beta blockers will reduce the risk of bleeding from small varices from 20% to 10% over a period of 3 years, resulting in significant cost savings to the NHS from better patient outcomes.
Detailed Description
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. We know that when varices are large we need to treat them with medication called beta-blockers to reduce the pressure in the varices. If the varices are small, we are not sure if we need to treat with beta-blockers and 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. We will observe them 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. We 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, and we will feedback to recruited patients the results at the end. We will assess the barriers and facilitators of doctors in primary care - such as General Practitioners - in adjusting the dose of the tablets to optimise treatment effects, and assess patients' views on taking part in the trial, and whether the side effects justify the potential benefits of reducing the risk of bleeding. We estimate this risk could be reduced from 20% of patients having significant bleeding to 10% over 3 years. We will measure the impact of beta-blockers on the overall costs to the NHS of caring for people with cirrhosis during the trial. We will then assess the impact of treatment on both mortality and quality of life using a combined measure, the Quality Adjusted Life-Year (QALY). We will use a mathematical prediction model to estimate the impact of treatment on costs, mortality and quality of life over a patient's lifetime. We will assess whether any increased costs are justified by better outcomes for patients and represent good value for money for the NHS budget. Finally, we will publish the results of the study 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cirrhosis, Liver, Portal Hypertension, Variceal Hemorrhage, Varices, Esophageal

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Triple-blinded
Allocation
Randomized
Enrollment
1200 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Carvedilol
Arm Type
Active Comparator
Arm Description
Oral Carvedilol 6.25 mg to 12.5 mg OD/ or 6.25mg BD (maximum dose 12.5mg)
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Oral tablet (1 or 2 tablets)
Intervention Type
Drug
Intervention Name(s)
Carvedilol
Intervention Description
Carvedilol, sold under the brand name Coreg among others, is a medication used to treat high blood pressure, congestive heart failure, and left ventricular dysfunction in people who are otherwise stable. For high blood pressure, it is generally a second-line treatment. It is taken by mouth.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Placebo
Primary Outcome Measure Information:
Title
Variceal Haemorrhage
Time Frame
3 years from recruitment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18 years and over Cirrhosis and portal hypertension, Small oesophageal varices diagnosed within the last 6 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 Exclusion Criteria: Non-cirrhotic portal hypertension Medium/large oesophageal varices (current or history [decreasing in size without curative therapy]), defined as >5 mm in diameter Gastric (IGV and GOV2), duodenal, rectal varices with or without evidence of recent bleeding. Previous variceal haemorrhage Previous band ligation or glue injection of oesophageal and/or gastric varices Red signs accompanying varices at endoscopy Known intolerance to beta blockers Contraindications to beta blocker use 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 period of IMP dosing Patients who have been on a CTIMP within the previous 3 months Clinical symptoms consistent with COVID-19
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Ruhama Uddin
Phone
0203 299 7142
Email
kch-tr.boppptrial@nhs.net
First Name & Middle Initial & Last Name or Official Title & Degree
Vishal Patel
Email
vishal.patel@nhs.net
Facility Information:
Facility Name
King's College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark McPhail
Email
mark.mcphail@kcl.ac.uk

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0263288
Description
Using a theory-informed approach to explore patient and staff perspectives on factors that influence clinical trial recruitment for patients with cirrhosis and small oesophageal varices
URL
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0275668
Description
General practitioner perspectives on factors that influence implementation of secondary care-initiated treatment in primary care: Exploring implementation beyond the context of a clinical trial

Learn more about this trial

Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of Oesophageal Varices Trial.

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