An RCT to Evaluate Different Treatment Approaches to Mitigate the Progression of Schistosomiasis Related Hepatic Fibrosis
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 600
- 试验地点
- 1
- 主要终点
- Improvement in liver fibrosis grade
研究概览
简要总结
The goal of this clinical trial is to learn if treating individuals living in Uganda who have liver fibrosis (scarring) due to schistosomiasis would benefit from more frequent treatment with drug praziquantel. This drug is already approved to treat schistosomiasis and is used globally. The study will include individuals who have schistosomiasis and some degree of liver fibrosis. The main questions it aims to answer are:
- Does treating participants three times per year as compared to once per year as currently recommended improve the likelihood the hepatic fibrosis will improve over three years.
- Does treating participants three times per year as compared to once per year as currently recommended decrease the risk they have for bleeding due to portal hypertension over three years.
- Is there a blood test that can tell us which individuals will experience worsening liver fibrosis before this happens.
Participants will:
Be screened for schistosomiasis using a urine test If participants have schistosomiasis they will undergo other screening procedures including a liver ultrasound, blood tests, and a physical exam if they have both schistosomiasis and liver (fibrosis) they will be invited to participate in the trial
If they are in the trial they will:
Take the drug praziquantel once per year or three times per year based on randomization for three years Have a liver ultrasound and blood samples for markers of liver fibrosis once per year Provide a urine sample to test for schistosomiasis each year
详细描述
The overarching goals of this proposal are to conduct a double blind, randomized controlled trial (RCT) (Phase III) among N=600 participants ages 15-40 in Lake Albert, Uganda, that will examine varying frequencies of treatment with Praziquantel (standard 40 mg/kg PO every 4 months or annually for three years) to identify approaches that best reverse or halt fibrosis as captured by ultrasound annually.
After excluding other causes of hepatic fibrosis, the trial will randomize/enroll N = 600 participants for the RCT (N = 150 individuals in each age and sex strata (4 sub-groups)) who have compensated schistosomal liver fibrosis based on the WHO "Niamey" ultrasound protocol for S. mansoni.
Using stratified randomization by subgroup treatment arms are as follows:
- Annual treatment (standard) arm: Participants in the annual treatment study arm will receive active study agent (PZQ at 40 mg/kg) at baseline and one, two, and three years post randomization and placebo at intervening 4 month visits (i.e. 4, 8, 16, 20, 28, 32 months post baseline).
- Every 4 months treatment (intervention) arm: Participants in this arm will receive praziquantel at a dose of 40 mg/kg every 4 months for 3 years. (i.e. at 4, 8, 12, 16, 20, 24, 28, 32 and 36 months post baseline).
Randomization and blinding The trial statistician will generate randomization codes by study number in blocks for each age/sex group and share with the pharmacist. Because the placebo and praziquantel tablets will be matched, allocation to a given study arm will be concealed to participants and study staff, including ultra-sonographers who are assessing study outcomes.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 15 Years 至 40 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •S. mansoni infection as determined by urine Circulating Cathodic Antigen (CCA)
- •Otherwise healthy as determined by history and physical examination conducted by the study clinician
- •Not Pregnant
- •Age 15-40 years
- •Consent for individuals 18 years of age and older, and parental consent and adolescent assent for participants ages 15-17 years.
- •The presence of hepatic fibrosis due to S. mansoni (Niamey protocol grade C-F) and compensated (without late-stage portal hypertension) after ruling out other causes of hepatic fibrosis as below.
排除标准
- •. History of upper gastrointestinal bleeding
- •Hepatic fibrosis that is not deemed to be due to schistosomiasis based on ultrasound and hepatitis serologies. For example, alcoholic cirrhosis or presence of chronic Hepatitis B or C by point of care test
- •Known neurocysticercosis or ocular cysticercosis
研究组 & 干预措施
Annual treatment (standard) with Praziquantel
Treatment with praziquantel once per year (standard recommendation)
干预措施: Praziquantel 40 mg/kg per dose given once annually (Drug)
Treatment with Praziquantel three times per year
Treatment with praziquantel three times per year (enhanced frequency)
干预措施: Praziquantel 40 mg/kg given three times per year (Drug)
结局指标
主要结局
Improvement in liver fibrosis grade
时间窗: three years
The primary outcome will be any improvement in grade of fibrosis (mild, moderate, severe) from baseline to study close out at three years.
次要结局
- Improvement in Severity of Portal Hypertension(Three years)
- Improvement in grade of liver fibrosis from baseline to two years(Two years)
- Improvement in severity of portal hypertension after two years(Two years)
- Improvement in grade of liver fibrosis at one year(one year)
- Improvement in severity of portal hypertension after one year(one year)
研究者
Jennifer Friedman, MD, PhD
Director, Center for International Health Research & Professor of Pediatrics
Rhode Island Hospital