Cirrhoses, LiverPhase 4BOPPPNCT03776955
Beta-blockers for Oesophageal Varices
A Phase 4 study testing Carvedilol in people with Cirrhoses, Liver and Oesophageal Varices, run by King's College Hospital NHS Trust at 4 sites in United Kingdom.
Trial summary
To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cirrhoses, Liver, Oesophageal Varices
- 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
- 1,200 participants
- Where
- 4 sitesUnited Kingdom
- Study dates
- 17 Jun 2019to Dec 2024
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- Cirrhosis and portal hypertension, defined by any 2 of the following:
- 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
Who cannot join
- 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
Show all 15Show fewer
- 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
Trial locations and contacts
4 sites in 1 country.
United Kingdom4 sites, 4 recruiting
- Not yet recruiting
Royal Victoria Hospital
Belfast, Northern Ireland, BT12 6BA
Angela Toner, 028 90633197, angela.toner@belfasttrust.hscni.net
Roger McCorry, MB BCh BAO, MRCP
- Not yet recruiting
Queen Elizabeth Hospital
Birmingham, B15 2TT
Emma Burke, 0121 3718451, Emma.Burke@uhb.nhs.uk
07770 827573
- Not yet recruiting
Royal London Hospital (Barts)
London, E1 1FR
James Hand, 020 3594 6773, James.Hand@nhs.net
Vikram Sharma, MBBS, MRCP, PhD, FRCP
- Recruiting
King's College Hosptial NHS Foundation Trust (Denmark Hill)
London
Ruhuma Uddin, BSc, 020 3299 7142, kch-tr.boppptrial@hs.uk
Mark McPhail
About this study
Official title: Beta-blockers or Placebo for Primary Prophylaxis of Oesophageal Varices (BOPPP Trial). A Blinded, Multi-centre, Clinical Effectiveness and Cost-effectiveness Randomised Controlled Trial
To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices
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.
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
- Cirrhoses, Liver, Oesophageal Varices
- Being tested
- Carvedilol
- Medical subject headings
- Esophageal and Gastric Varices
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CarvedilolDrug
Oral tablet
| Study group | Role | What they receive |
|---|---|---|
| Oral Carvedilol | Experimental | 6.25 mg or 12.5 mg if tolerated Receives: Drug: Carvedilol |
| Oral Placebo | Placebo comparator | Not described Receives: Drug: Carvedilol |
What is being measured
The primary outcome is the main question the study is designed to answer.
Variceal bleeding
Time to first variceal haemorrhage
Measured: 3 years
Health Economic assessment
Assess the cost effectiveness of early intervention with non specific beta blockers in this patient population.
Measured: 3 years
Secondary outcomes (8)
Variceal bleed rate
Number of variceal bleeds by allocation
Measured: 1 and 3 years
Variceal bleeding needing intervention
Number of patients that progress to medium/large varices requiring clinical intervention
Measured: 3 years
Composite of variceal bleed rate and bleeding needing intervention
Composite of variceal bleed rate and bleeding needing intervention. i.e. Unit less measure of rate of ((Number of patients who bled) PLUS (Number of patients who progressed without bleeding)) / (Number of patients in that arm at randomisation) at 3 years ranging from 0 to 1
Measured: 3 years
Clinical decompensation
Number of patients with clinical decompensation (spontaneous bacterial peritonitis, new ascites, new hepatic encephalopathy) in the active and inactive IMP groups
Measured: 3 years
Child Pugh Score for Cirrhosis mortality
Child Pugh Score for Cirrhosis mortalityin the active and inactive IMP groups. Range 5-15. Higher scores represent worse outcomes.
Measured: 3 years
Model for end-stage liver disease (MELD) score
MELD score in the active and inactive IMP groups.Range 6-40. Higher scores represent worse outcomes.
Measured: 3 years
Survival (Overall, liver related, cardio-vascular related)
Survival (Overall, liver related, cardio-vascular related)
Measured: 3 years
Quality of life assessment
Quality of life score using EQ5D-5L in the active and inactive IMP groups. Range 5-25. Higher scores represent worse outcomes.
Measured: 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2018
- Study start17 Jun 2019
- Primary completionSep 2024 (estimated)
- Study completionDec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cirrhoses, LiverStudies of the same condition, open and under way.
- 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
- 1,200 participants (estimated)
Sponsor and investigators
- Lead sponsor
- King's College Hospital NHS Trust
- Sponsor type
- University, hospital or other
- Collaborators
- King's College London, Guy's and St Thomas' NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, Cardiff University, Brighton and Sussex University Hospitals NHS Trust
- Responsible party
- Sponsor
- Investigators
- Mark McPhail, BSc, PhD, MB ChB, Study director, King's College Hospital NHS TrustBen Carter, BSc, PhD, Study director, King's College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03776955
- Sponsor's protocol ID
- 125861
- Acronym
- BOPPP
- Status last verified
- Oct 2019
- First submitted
- 30 Nov 2018
- Last updated
- 3 Oct 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: To be decided
Study at a glance
From the registry record, last updated by the sponsor on 3 Oct 2019. 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, Multi-centre, Clinical Effectiveness and Cost-effectiveness Randomised Controlled Trial
- ClinicalTrials.gov ID
- NCT03776955
- Acronym / sponsor ID
- BOPPP / 125861
- Conditions
- Cirrhoses, Liver, Oesophageal Varices
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 1,200 participants (estimated)
- Lead sponsor
- King's College Hospital NHS TrustUniversity, hospital or other
- Collaborators
- King's College London, Guy's and St Thomas' NHS Foundation Trust, St George's University Hospitals NHS Foundation Trust, Cardiff University, Brighton and Sussex University Hospitals NHS Trust
- Study start
- 17 Jun 2019 (actual)
- Primary completion
- Sep 2024 (estimated)
- Study completion
- Dec 2024 (estimated)
- First posted
- 17 Dec 2018 (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.
To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices
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.
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.
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 |
|---|---|---|
| Oral Carvedilol | Experimental | Drug: Carvedilol6.25 mg or 12.5 mg if tolerated |
| Oral Placebo | Placebo comparator | Drug: Carvedilol |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age >18 years
- Cirrhosis and portal hypertension, defined by any 2 of the following:
- 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
Key exclusion criteria (15 listed)
- 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
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 |
|---|---|---|
| CarvedilolOral tablet | Drug | Oral Carvedilol, Oral Placebo |
Primary outcome
Variceal bleeding
Time frame: 3 years
Time to first variceal haemorrhage
Health Economic assessment
Time frame: 3 years
Assess the cost effectiveness of early intervention with non specific beta blockers in this patient population.
8 secondary outcomes
Variceal bleed rate
Time frame: 1 and 3 years
Variceal bleeding needing intervention
Time frame: 3 years
Composite of variceal bleed rate and bleeding needing intervention
Time frame: 3 years
Clinical decompensation
Time frame: 3 years
Child Pugh Score for Cirrhosis mortality
Time frame: 3 years
Model for end-stage liver disease (MELD) score
Time frame: 3 years
Survival (Overall, liver related, cardio-vascular related)
Time frame: 3 years
Quality of life assessment
Time frame: 3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Oct 2019.
- Individual participant dataSharing planned: Undecided. To be decided
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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, BSc, PhD, MB ChB study director
King's College Hospital NHS Trust
Ben Carter, BSc, PhD study director
King's College London
4 sites 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 Cirrhoses, Liver and Oesophageal Varices, run by King's College Hospital NHS Trust at 4 sites 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 6 inclusion and 15 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: status not confirmed, as of the sponsor's last update on 3 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Vishal Patel, BSc, MBBS, MRCP, MPhil (+44 (0)20 3299 3654, vishal.patel@nhs.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Variceal bleeding (time frame: 3 years). The study lists 2 primary outcomes in all. 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 3 Oct 2019.