Cirrhosis, LiverPhase 4BOPPPNCT05872698
Beta-blockers or Placebo for Primary Prophylaxis (BOPPP) of Oesophageal Varices Trial.
A Phase 4 study testing Carvedilol in people with Cirrhosis, Liver and Portal Hypertension, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhosis, Liver, Portal Hypertension, Variceal Hemorrhage
- What is being tested?
- Carvedilol
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 763 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 1 Apr 2019to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 17Show fewer
- 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, if relevant
- Patients who have been on a CTIMP within the previous 3 months
- Clinical symptoms consistent with COVID-19
Trial locations and contacts
1 site in 1 country.
About this study
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.
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.
Read the 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.
- Being tested
- Carvedilol, Placebo
- Medical subject headings
- Liver Cirrhosis, Hypertension, Portal, Esophageal and Gastric Varices
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
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.
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Carvedilol | Active comparator | Oral Carvedilol 6.25 mg to 12.5 mg OD/ or 6.25mg BD (maximum dose 12.5mg) Receives: Drug: Carvedilol |
| Placebo | Placebo comparator | Oral tablet (1 or 2 tablets) Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to All-Cause Decompensation
All-cause decompensation is defined as the occurrence of any of the below:
Liver-related mortality Variceal haemorrhage Spontaneous bacterial peritonitis Hepatorenal syndrome New or worsening hepatic encephalopathy New or worsening ascites Sustained increase in Child Pugh Grade by 1 grade or MELD by 5 points
Measured: up to 3 years from recruitment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2023
- Study start1 Apr 2019
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhosis, LiverStudies of the same condition, open and under way.
- More trials run by King's College Hospital NHS TrustThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 763 participants (actual)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London, Cardiff University, Brighton and Sussex University Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- Mark McPhail, Principal investigator, King's College Hospital NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05872698
- Sponsor's protocol ID
- 255446
- Acronym
- BOPPP
- Status last verified
- Apr 2026
- First submitted
- 21 Jan 2021
- Last updated
- 1 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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.
- ClinicalTrials.gov ID
- NCT05872698
- Acronym / sponsor ID
- BOPPP / 255446
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 763 participants (actual)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London, Cardiff University, Brighton and Sussex University Hospitals NHS Trust
- Study start
- 1 Apr 2019 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 24 May 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Carvedilol | Active comparator | Drug: CarvedilolOral Carvedilol 6.25 mg to 12.5 mg OD/ or 6.25mg BD (maximum dose 12.5mg) |
| Placebo | Placebo comparator | Drug: PlaceboOral tablet (1 or 2 tablets) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (17 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CarvedilolCarvedilol, 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. | Drug | Carvedilol |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Time to All-Cause Decompensation
Time frame: up to 3 years from recruitment
All-cause decompensation is defined as the occurrence of any of the below: Liver-related mortality Variceal haemorrhage Spontaneous bacterial peritonitis Hepatorenal syndrome New or worsening hepatic encephalopathy New or worsening ascites Sustained increase in Child Pugh Grade by 1 grade or MELD by 5 points
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 May 2026.
- 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 varicesLink provided by the sponsor.
- General practitioner perspectives on factors that influence implementation of secondary care-initiated treatment in primary care: Exploring implementation beyond the context of a clinical trialLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Mark McPhail principal investigator
King's College Hospital NHS Trust
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Carvedilol in people with Cirrhosis, Liver and Portal Hypertension, run by King's College Hospital NHS Trust at 1 site in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 1 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to All-Cause Decompensation (time frame: up to 3 years from recruitment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 May 2026.