NCT01638559已完成2 期
Immunosuppression Withdrawal for Stable Pediatric Liver Transplant Recipients
National Institute of Allergy and Infectious Diseases (NIAID)12 个研究点 分布在 2 个国家目标入组 161 人开始时间: 2012年8月14日最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 161
- 试验地点
- 12
- 主要终点
- Number of Operationally Tolerant Participants
研究概览
简要总结
The primary objective of this study is to assess the efficacy of immunosuppression withdrawal (ISW) in pediatric liver transplant (tx) recipients.
详细描述
Anti-rejection medicines, also known as immunosuppressive drugs, are prescribed to organ transplant recipients to prevent rejection of the new organ. Long-term use of these medicines places transplant recipients at higher risk of serious infections and certain types of cancer.
This study seeks to:
- Find out if it is safe to slowly reduce and then completely stop the immunosuppression taken by children who have received liver transplants. This process is called 'immunosuppression withdrawal'or ISW.
- Find blood or liver biopsy tests that can help transplant doctors in the future to predict if it is safe to decrease or stop immunosuppression drugs in children who have had a liver transplant.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- — 至 18 Years（Child, Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject and/or parent guardian must be able to understand and provide informed consent;
- •Is the recipient of a living or deceased donor liver tx when subject was less than or equal to 6 years of age;
- •Is at least 4 years post-tx at the time of study enrollment;
- •Has normal allograft function defined as Alanine aminotransferase (ALT) < 50 IU/l and gamma-glutamyl transferase (GGT) < 50 IU/l;
- •Has no evidence of acute rejection (AR) or chronic rejection (CR) within the past 2 years, based on medical history;
- •Is stable on IS monotherapy with a calcineurin inhibitor (CNI);
- •For female subjects of childbearing potential, subject must have a negative pregnancy test upon study entry;
- •For female and male subjects with reproductive potential, subject must agree to use FDA approved methods of birth control for the duration of the study;
- •Must be negative for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection within one year of enrollment;
- •Must have screening biopsy that fulfills, based on central pathology reading, the following criteria:
- •Portal inflammation and interface activity: Preferably absent, but minimal to focal mild portal mononuclear inflammation may be present. Interface necro-inflammatory activity is absent or equivocal/minimal and, if present, involves a minority of portal tracts.
- •Centrizonal/peri-venular inflammation: Preferably absent, but minimal to focal mild perivenular mononuclear inflammation may be present. Perivenular necro-inflammatory activity is absent or equivocal/minimal and, if present, involves a minority of terminal hepatic venules.
- •Bile duct changes: No lymphocytic bile duct damage, ductopenia and biliary epithelial senescence changes, unless there is an alternative, non-immunologic explanation (e.g. biliary strictures).
- •Fibrosis: < Ishak Stage 3 (i.e. not more than occasional portal-to-portal bridging). Perivenular fibrosis should be less than "moderate", according to Banff Criteria.
- •Arteries: Negative for obliterative or foam cell arteriopathy.
排除标准
- •Have received a liver tx for autoimmune liver disease, including autoimmune hepatitis or primary sclerosing cholangitis;
- •Have received a liver tx for hepatitis B or hepatitis C;
- •Have received a second organ transplant before, simultaneously, or after liver tx;
- •Have a calculated glomerular filtration rate (modified Schwartz formula) of less than 60 mL/min/1.73 m^2;
- •Have had a 50 percent (%) dose increase in CNI within 6 months of screening;
- •Have discontinued a second IS agent within 12 months of screening;
- •Have any systemic illness requiring or likely to require chronic or recurrent use of IS;
- •Is pregnant or breastfeeding;
- •Is unwilling or unable to adhere with study requirements and procedures;
- •Have mental illness or history of drug or alcohol abuse that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements;
- •Is unwilling or unable to provide consent or comply with the study protocol;
- •Has used investigational drugs within 4 weeks of enrollment;
- •Is receiving treatment for HIV infection;
- •Has received any licensed or investigational live attenuated vaccine(s) within two months of enrollment;
- •Has any medical condition that, in the opinion of the investigator, will interfere with safe participation in the trial.
研究组 & 干预措施
Immunosuppression withdrawal
Experimental
Gradual withdrawal of immunosuppressive treatment withdrawal as per protocol.
干预措施: Immunosuppression withdrawal (Drug)
结局指标
主要结局
Number of Operationally Tolerant Participants
时间窗: 12 Months after complete immunosuppression withdrawal
Number of participants that are operationally tolerant, defined as those who successfully withdraw from immunosuppression and maintain normal allograft status as assessed by liver biopsy and liver tests 12 months after complete immunosuppression withdrawal.
次要结局
- Number of Participants With Clinical Complications Usually Attributed to Immunosuppression(Time from immunosuppression withdrawal through a minimum of 36 months and a maximum of 48 months of follow-up)
- Clinical Severity of Acute Rejection(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
- Time to Increased Immunosuppression or Re-Initiation of Immunosuppression(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
- Number and Severity of Biopsies Read as Histologic Acute Rejection(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
- Reason for Discontinuation of Withdrawal(Time from start of immunosuppression withdrawal through discontinuation of withdrawal, a maximum of 52 weeks)
- Change in Immunosuppression Medication (Calcineurin Inhibitor) Dose From Start of Immunosuppression Withdrawal to the Time of Immunosuppression Withdrawal Failure(Time from starting immunosuppression withdrawal until immunosuppression withdrawal failure, maximum 52 weeks)
- Time to Resolution of Rejection(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
- Change in Child Health Related Quality of Life Scores Between Tolerant and Non-tolerant Subjects(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
- Impact of Immunosuppression Withdrawal (ISW) on Allograft Histology(Time from screening biopsy to end of study (month 48) biopsy)
- Duration of Operational Tolerance(Time from immunosuppression withdrawal through a minimum of 36 months and a maximum of 48 months of follow-up)
- Change in Immunosuppression Medication Dose From Study Initiation of Withdrawal to the End of the Study(Time from immunosuppression withdrawal through a minimum of 36 months and maximum of 48 months of follow-up)
研究者
研究点 (12)
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