A Multi-center Randomized Controlled Study of Primary Prevention of Esophageal Variceal Bleeding in Cirrhotic Patients Treated With HVPG-guided Beta- Blocker Therapy or Standard Heart Rate-guided Beta-blocker Therapy
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 78
- 试验地点
- 8
- 主要终点
- First variceal bleeding episodes
研究概览
简要总结
Study hypothesis:
Hepatic venous pressure gradient (HVPG)-directed primary prophylaxis with nonselective beta-blocker therapy (NSBB) leads to a reduction in first variceal bleeding episodes and is cost-effective in the long term.
Study design:
A multi-center randomized controlled study comparing nonselective beta-blocker therapy guided by the hemodynamic response as determined by the difference in HVPG before and after starting oral NSBB therapy, to standard heart rate-guided NSBB therapy in patients with esophageal varices due to liver cirrhosis without a history of esophageal variceal hemorrhage.
Primary study parameters/outcome of the study:
First variceal bleeding episodes occurring within the first two years.
Secondary study parameters/outcome of the study:
- Mortality
- Occurrence of other cirrhosis-related complications
- Occurrence of hepatocellular carcinoma
- Costs of treatments
- Adverse effects
详细描述
Background of the study:
About 50% of cirrhotic patients who use nonselective beta-blockers (NSBB) for primary prevention of variceal bleeding do not reach target hemodynamic response, defined as HVPG < 12 mmHg or a > 20% decrease in HVPG from baseline. These so-called hemodynamic nonresponding patients have significantly higher rate of first esophageal variceal hemorrhage as compared to patients who do respond to NSBB.
International institutions that publish guidelines differ in their recommendations concerning HVPG monitoring. As a result, practice currently varies widely.
The investigators hypothesize that HVPG-directed primary prophylaxis leads to a reduction in first variceal bleeding episodes and is cost-effective in the long term.
Objective of the study:
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with liver cirrhosis Large (≥5 mm) esophageal varices
排除标准
- •History of esophageal variceal hemorrhage
- •Pregnancy
- •Contraindications to beta-blocker therapy
- •Esophageal varices in the absence of liver cirrhosis
- •Intermediate, advanced or terminal stage hepatocellular carcinoma (BCLC stage B, C or D)
- •Refractory ascites
- •Hepatorenal syndrome
- •Prior treatment or prophylaxis for esophageal varices or varices bleeding (propranolol use, TIPS, endoscopic banding ligation, endoscopic sclerotherapy)
研究组 & 干预措施
HVPG-propranolol arm
A baseline hepatic venous pressure gradient measurement (HVPG measurement) is performed in day-care setting. After this procedure propranolol is started at 20 mg BID. with dose escalation as described in the propranolol arm.
A second HVPG measurement is performed at 4 weeks after adequate propranolol therapy. In patients who reach target HVPG reduction (responders), propranolol is continued at the same dose without routine control endoscopy. In patients who do not reach target HVPG reduction (nonresponders), endoscopic band ligation is performed in day-care setting with intervals of 2-4 weeks until complete obliteration of varices. Follow-up endoscopy with 6 months interval is performed to detect and treat recurrent large varices.
干预措施: Hepatic venous pressure gradient measurement (Procedure)
Propranolol arm
Propranolol start 20 mg BID. orally with dose escalation based on heart frequency (HF) with 3-days interval to the maximum tolerated dose. No routine control endoscopy is required.
结局指标
主要结局
First variceal bleeding episodes
时间窗: two years of follow-up
First variceal bleeding episodes
次要结局
- Mortality(two years)
- Occurrence of other cirrhosis-related complications(two years)
- Costs of treatments(two years)
- Adverse effects(two years)
研究者
Dr. M.J.Coenraad
Dr.
Leiden University Medical Center