Beta-blockers for Oesophageal Varices (BOPPP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT03776955|
Recruitment Status : Recruiting
First Posted : December 17, 2018
Last Update Posted : October 3, 2019
|Condition or disease||Intervention/treatment||Phase|
|Cirrhoses, Liver Oesophageal Varices||Drug: Carvedilol||Phase 4|
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 Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||1200 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Masking Description:||Placebo matched control|
|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|
|Actual Study Start Date :||June 17, 2019|
|Estimated Primary Completion Date :||September 2024|
|Estimated Study Completion Date :||December 2024|
Experimental: Oral Carvedilol
6.25 mg or 12.5 mg if tolerated
|Placebo Comparator: Oral Placebo||
- 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.
- Variceal bleed rate [ Time Frame: 1 and 3 years ]Number of variceal bleeds by allocation
- Variceal bleeding needing intervention [ Time Frame: 3 years ]Number of patients that progress to medium/large varices requiring clinical intervention
- Composite of variceal bleed rate and bleeding needing intervention [ Time Frame: 3 years ]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
- Clinical decompensation [ Time Frame: 3 years ]Number of patients with clinical decompensation (spontaneous bacterial peritonitis, new ascites, new hepatic encephalopathy) in the active and inactive IMP groups
- Child Pugh Score for Cirrhosis mortality [ Time Frame: 3 years ]Child Pugh Score for Cirrhosis mortalityin the active and inactive IMP groups. Range 5-15. Higher scores represent worse outcomes.
- Model for end-stage liver disease (MELD) score [ Time Frame: 3 years ]MELD score in the active and inactive IMP groups.Range 6-40. Higher scores represent worse outcomes.
- Survival (Overall, liver related, cardio-vascular related) [ Time Frame: 3 years ]Survival (Overall, liver related, cardio-vascular related)
- Quality of life assessment [ Time Frame: 3 years ]Quality of life score using EQ5D-5L in the active and inactive IMP groups. Range 5-25. Higher scores represent worse outcomes.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03776955
|Contact: Vishal Patel, BSc, MBBS, MRCP, MPhil||+44 (0)20 3299 email@example.com|
|Contact: Kieran Brack, BSc, PhD||+44 (0)20 3299 firstname.lastname@example.org|
|Royal Victoria Hospital||Not yet recruiting|
|Belfast, Northern Ireland, United Kingdom, BT12 6BA|
|Contact: Angela Toner 028 90633197 email@example.com|
|Principal Investigator: Roger McCorry, MB BCh BAO, MRCP|
|Queen Elizabeth Hospital||Not yet recruiting|
|Birmingham, United Kingdom, B15 2TT|
|Contact: Emma Burke 0121 3718451 Emma.Burke@uhb.nhs.uk|
|Contact 07770 827573|
|Principal Investigator: Dhiraj Tripathi, MBChB, MD|
|Royal London Hospital (Barts)||Not yet recruiting|
|London, United Kingdom, E1 1FR|
|Contact: James Hand 020 3594 6773 James.Hand@nhs.net|
|Principal Investigator: Vikram Sharma, MBBS, MRCP, PhD, FRCP|
|King's College Hosptial NHS Foundation Trust (Denmark Hill)||Recruiting|
|London, United Kingdom|
|Contact: Ruhuma Uddin, BSc 020 3299 7142 firstname.lastname@example.org|
|Principal Investigator: Mark McPhail|
|Study Director:||Mark McPhail, BSc, PhD, MB ChB||King's College Hospital NHS Trust|
|Study Director:||Ben Carter, BSc, PhD||King's College London|