Beta-blockers or Placebo for Primary Prophylaxis of Oesophageal Varices (BOPPP Trial). A Blinded, Multi-centre, Clinical Effectiveness and Cost-effectiveness Randomised Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 发起方
- 入组人数
- 1,200
- 试验地点
- 4
- 主要终点
- Health Economic assessment
研究概览
简要总结
To determine if carvedilol reduces the rate of variceal haemorrhage in patients with cirrhosis and small oesophageal varices
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Placebo matched control
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >18 years
- •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
- •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
排除标准
- •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
- •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
研究组 & 干预措施
Oral Carvedilol
6.25 mg or 12.5 mg if tolerated
干预措施: Carvedilol (Drug)
Oral Placebo
干预措施: Carvedilol (Drug)
结局指标
主要结局
Health Economic assessment
时间窗: 3 years
Assess the cost effectiveness of early intervention with non specific beta blockers in this patient population.
Variceal bleeding
时间窗: 3 years
Time to first variceal haemorrhage
次要结局
- Clinical decompensation(3 years)
- Child Pugh Score for Cirrhosis mortality(3 years)
- Variceal bleed rate(1 and 3 years)
- Variceal bleeding needing intervention(3 years)
- Composite of variceal bleed rate and bleeding needing intervention(3 years)
- Model for end-stage liver disease (MELD) score(3 years)
- Survival (Overall, liver related, cardio-vascular related)(3 years)
- Quality of life assessment(3 years)