A Multicenter, Randomized, Open-Label, Active-Controlled, Trial to Evaluate the Safety and Efficacy of Rifaximin 550 mg With and Without Lactulose in Subjects With a History of Recurrent Overt Hepatic Encephalopathy
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 222
- 试验地点
- 36
- 主要终点
- Number of Participants Reporting a First Breakthrough HE Episode
研究概览
简要总结
The purpose of the study is to evaluate if rifaximin alone or rifaximin plus lactulose delays the onset of hepatic encephalopathy (HE) in participants with cirrhosis who have had a previous episode of HE.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or non-pregnant, non-lactating females greater than or equal to (≥) 18 years old.
- •In remission from demonstrated overt HE (Conn score 0 or 1).
- •Have had one or more episodes of overt HE associated with cirrhosis within 6 months prior to screening visit (Day -7 to -1).
- •Participant has a close family member or other personal contact who is familiar with the participant's HE and can provide continuing oversight to the participant and is willing to perform as caregiver for the participant during the conduct of the trial.
排除标准
- •Participant has been diagnosed with human immunodeficiency virus (HIV) as determined by medical history.
- •History of tuberculosis infection.
- •Participant has been diagnosed with chronic respiratory insufficiency.
- •Participant has been diagnosed with a current infection for which they are currently taking oral or parenteral antibiotics.
- •Renal insufficiency requiring routine dialysis.
- •Participant has an active spontaneous bacterial peritonitis(SBP) infection.
- •Intestinal obstruction or inflammatory bowel disease.
- •Participant has active malignancy within the last 5 years prior to screening visit, except basal cell carcinoma of the skin, or if female, in situ cervical carcinoma that has been surgically excised.
- •Current gastrointestinal (GI) bleeding or has a history of a GI hemorrhage of sufficient severity to require hospitalization and a transfusion of ≥2 units of blood within 3 months prior to screening visit.
- •Participant is anemic, as defined by a hemoglobin of less than (<) 8 grams/deciliter (g/dL).
- •Scheduled to receive a liver transplant within 1 month of screening.
研究组 & 干预措施
Rifaximin 550 mg BID
Participants will receive rifaximin 550 milligrams (mg) tablet orally twice daily (BID) for 24 weeks.
干预措施: Rifaximin (Drug)
Rifaximin 550 mg BID + Lactulose
Participants will receive rifaximin 550 mg tablet orally BID with lactulose solution for 24 weeks. Lactulose dose will be self-titrated by the participant to produce 2 to 3 soft stools per day.
干预措施: Rifaximin (Drug)
Rifaximin 550 mg BID + Lactulose
Participants will receive rifaximin 550 mg tablet orally BID with lactulose solution for 24 weeks. Lactulose dose will be self-titrated by the participant to produce 2 to 3 soft stools per day.
干预措施: Lactulose (Drug)
结局指标
主要结局
Number of Participants Reporting a First Breakthrough HE Episode
时间窗: From randomization (Day 1) up to Day 170
A breakthrough HE episode was defined as an increase of the Conn score to Grade greater than or equal to (≥) 2 (ie, 0 or 1 to ≥ 2). Conn score is widely used as a measure of mental state in HE. The scale used in Conn scoring system include: Grade 0=No personality or behavioral abnormality; Grade 1=Trivial lack of awareness, euphoria, or anxiety; shortened attention span, impairment of addition or subtraction; Grade 2=Lethargy, disorientation for time, obvious personality change, inappropriate behaviour; Grade 3=Somnolence to semi-stupor, responsive to stimuli, confused, gross disorientation, bizarre behaviour; Grade 4=Coma, unable to test mental state. The time to the first breakthrough HE episode was defined as the duration between the date of first dose of study drug and the date of first breakthrough HE episode. Number of participants reporting a first breakthrough HE episode during randomization to Month 6 is presented.
次要结局
- Number of Participants Who Died Due to Any Reason(From randomization (Day 1) up to end of study (Day 186))
- Number of Participants Who Were Hospitalized Due to HE Episode(From randomization (Day 1) up to Day 170)