A Randomized, Open-label,Controlled Phase II b Study to Demonstrate Efficacy and Safety of Sirolimus Chronic Rejection After Lung Transplant
试验速览
- 阶段
- 2 期
- 状态
- 撤回
- 主要终点
- Death
研究概览
简要总结
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).To assess the efficacy and safety of sirolimus plus tacrolimus and prednisone
(S) compared to standard therapy (tacrolimus, mycophenolate mofetil
(MMF) and prednisone) (ST) for chronic rejection, defined as grades 1 and 2
bronchiolitis obliterans syndrome (BOS); BOS defined as ≥ 20% decline
from maximal post-transplant FEV1.
详细描述
This is a prospective single-center, open-label, randomized, controlled pilot
study in the treatment of chronic rejection (CR), defined as grade 1 and 2
BOS, in adult recipients of a pulmonary allograft (single or double lungs).
Patients meeting entry criteria shall demonstrate a sustained decline in FEV1
having met stage 1 or 2 BOS. Patients randomized to the study arm, will be
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
- •Age: 18 or older.
- •Recipient of a single or double pulmonary allograft at least twelve months before study entry.
- •Clinically diagnosed BOS grade 1 or 2
- •Receiving oral TAC-based immunosuppression according to institutional standards.
- •Capable of understanding the purposes and risks of the study, has given written informed consent and agrees to comply with the study requirements and capable of protocol adherence.
- •Women of childbearing potential must have a negative serum pregnancy test within 7 days prior to study entry.
- •Stable to enable routine pre and post-transplant bronchoscopy with BAL and biopsy.
- •Fasting cholesterol < 250 mg/dL, fasting triglycerides < 250 mg/dL -
排除标准
- •Active bacterial, viral or fungal infection not successfully resolved at least 4 weeks prior to study entry.
- •Mechanical ventilation.
- •At screening FEV1 < 1 liter and/or < FEV1 of 25 % predicted.
- •Pregnant women or women who are unwilling to use appropriate birth control to avoid pregnancy.
- •Women who breastfeed.
- •Known hypersensitivity to sirolimus.
- •Serum creatinine value of > 2.5 mg/dL or chronic dialysis use or liver disease with a bilirubin > 2 mg/dL.
- •Subjects with severe underlying disease other than BOS that is thought to become fatal within four months of clinical assessment.
- •Receipt of an investigational drug as part of a clinical trial within 4 weeks prior to study entry. This is defined as any treatment that is implemented under an Investigational New Drug.
- •Psychiatric disorders or altered mental status precluding understanding of the informed consent process and/or completion of the necessary procedures.
- •Any co-existing medical condition that in the Investigator's judgment will substantially increase the risk associated with the patient's participation in the clinical trial.
- •Clinically significant bronchial strictures unresponsive to dilatation procedures.
- •Subjects with malignancy diagnosed within one year prior to screen (with the exception of skin cancers).
- •Lipid panel fasting cholesterol > 250 mg/dL, fasting triglycerides >250 mg/dL
研究组 & 干预措施
Sirolimus and Tacrolimus and prednisone
Assigned Interventions Sirolimus (Rapamune) Tacrolimus (Prograft) Prednisone (Deltasone, Prednicot, Rayos, Sterapred)
干预措施: Assigned Interventions (Drug)
Standard of Care
Arm1:) sirolimus and tacrolimus and prednisone group:
Tacrolimus, The patient will receive 0.1-0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 5-12 ng/ml.
Mycophenolate mofetil (NA )Stopped upon sirolimus initiation Sirolimus:1-5 mg/day PO if >40 kg / 1 mg/m²/day if <40 kg trough blood levels 5-12 ng/ml Prednisone:20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effects.
Arm 2) Standard Therapy Tacrolimus:0.1 to 0.15 mg/kg/day PO in 2 divided doses Adjust trough blood 8-12 ng/ml Mycophenolate mofetil:750-1250 mg bid PO and adjust to tolerance (WBCs and GI side effects Sirolimus: NA Prednisone: Prednisone dose 20 mg/day PO if >40 kg and 10 mg/day if <40 kg, adjust based on adverse effect
干预措施: Assigned Interventions (Drug)
结局指标
主要结局
Death
时间窗: 2 years
Increase in motility
FEV1 (Forced Respiratory Volume in 1 second)
时间窗: 2 years
Greater or equal to 20% decline in FEV1 from randomization
Re-Transplantation
时间窗: 2 years
Increase in re-transplantation from baseline
次要结局
- FVC (Forced Vital Capacity)(2 years)
- FEF (forced expiratory flow)(2 years)