Rifaximin Versus Norfloxacin in the Primary Prophylaxis of Spontaneous Bacterial Peritonitis
试验速览
- 阶段
- 3 期
- 发起方
- 入组人数
- 322
- 试验地点
- 1
- 主要终点
- Prevention of Spontaneous Bacterial Peritonitis
研究概览
简要总结
Background
Prophylaxis of SBP is indicated in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid, and patients with a previous history of SBP (secondary prophylaxis).
Selective intestinal decontamination with norfloxacin, a quinolone with relatively poor gastrointestinal absorption and with antibacterial activity against GNB, is the most commonly used regimen, but several concerns have been recently raised in this regard.
A recent network meta-analysis published by the investigators showed that rifaximin determines interesting results in this setting but needs to be tested in further trials.
Given its favorable safety profile and the relatively low cost, rifaximin could represent the antibiotic of choice in long-term prophylaxis.
Study Objective To establish the prophylactic efficacy, of rifaximin as compared to norfloxacin in cirrhotic patients with low protein content in the ascitic fluid.
Protocol design Phase III, two-arms, open-label, multi-center, randomized controlled trial.
Trial population Patients with cirrhosis and ascites and with low protein content in the ascitic fluid (≤1.5 g/dL) and with deteriorated liver function (Child-Pugh score ≥B9, serum bilirubin level ≥3 mg/dL) or impaired renal function (creatinine ≥1.2 mg/dL blood urea nitrogen level ≥25 mg/dL or hyponatremia ≤130 milliequivalent [mEq]/L)
Protocol Treatments
- The Treatment arm will undergo rifaximin 1200 mg/day in 3 doses.
- The Control arm will undergo norfloxacin 400 mg 1/die for 6 months
Primary Endpoint Prevention of spontaneous bacterial peritonitis episodes.
Secondary Endpoints
- Prevention of mortality (both all-cause and liver-related mortality)
- Preventions of hepatorenal syndrome
- Prevention of other infections
- Adverse events
Sample size and study duration It will be planned to enroll 322 patients (161 per arms) within 18 months. A minimum follow up of 6 months from the last patient recruited will be required.
详细描述
Background
Spontaneous bacterial peritonitis (SBP) is a commonly observed and severe complication in patients with cirrhosis and ascites, with a reported prevalence ranging from 10% to 25% in hospitalized cirrhotic patients1.
Given the high mortality rate and the risk of developing hepato-renal syndrome (HRS), prophylaxis of SBP is indicated particularly in three high-risk populations: patients with acute gastrointestinal hemorrhage, patients with low total protein content in ascitic fluid, and patients with a previous history of SBP (secondary prophylaxis)2.
The ideal prophylactic agent should be safe, affordable, and effective particularly against anaerobic bacteria translocating from the gut as most episodes of SBP are thought to result from the translocation of enteric Gram-negative bacilli (GNB)3.
Selective intestinal decontamination with norfloxacin, a quinolone with relatively poor gastrointestinal absorption and with antibacterial activity against GNB, is the most commonly used regimen4, but several concerns have been recently raised in this regard. In fact, the epidemiology of bacterial infections in cirrhosis is evolving with an increasing incidence of infections caused by quinolone-resistant bacteria5; moreover, primary prophylaxis in low-protein ascitic patients requires long-term antibiotic regimens (whose exact duration is still matter of debate), hence less expensive and better tolerated agents such as rifaximin have been tested with conflicting results6.
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
- None
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
- •Adult patients with cirrhosis and ascites and with low protein content in the ascitic fluid (≤1.5 g/dL) and with deteriorated liver function (Child-Pugh score ≥B9, serum bilirubin level ≥3 mg/dL) or impaired renal function (creatinine ≥1.2 mg/dL blood urea nitrogen level ≥25 mg/dL or hyponatremia ≤130 mEq/L)
排除标准
- •Age under 18 years
- •Previous history of SBP
- •Previous use of antibiotics within the previous two weeks
- •Previous GIT bleeding within one month
- •Resolving ascites for one month after diuretic therapy
- •Liver malignancy, organic renal disease
- •Human immunodeficiency virus infection
- •Known hypersensitivity to planned drugs
- •Refusal to provide informed consent.
研究组 & 干预措施
Intervention Group
Rifaximin 1200 mg/day in 3 doses
干预措施: Rifaximin (Drug)
Control Group
Norfloxacin 400 mg/day in one dose
干预措施: Norfloxacin (Drug)
结局指标
主要结局
Prevention of Spontaneous Bacterial Peritonitis
时间窗: 6 months
Rate of episodes of spontaneous bacterial peritonitis
次要结局
- Prevention of mortality(6 months)
- Prevention of other infections(6 months)
- Prevention of hepatorenal syndrome(6 months)
- Adverse Events(6 months)
研究者
Antonio Facciorusso
Principal Investigator
Ospedali Riuniti di Foggia