Clinical Outcome of Delayed or Standard Prograf Together With Induction Therapy Followed by Conversion to Advagraf in Donation After Cardiac (or Circulatory) Death (DCD) Kidney Transplant Recipients: A Randomized, Open-label, Multicenter Clinical Trial
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 284
- 试验地点
- 14
- 主要终点
- Incidence of delayed graft function (DGF)
研究概览
简要总结
The purpose of this study is to confirm non-inferiority of delayed Prograf treatment to standard Prograf treatment in the incidence of delayed graft function (DGF) within 1 week between the 2 immunosuppressive (IS) treatment groups: delayed or standard Prograf together with induction therapy, and then convert to Advagraf usage in donation after cardiac (or circulatory) death (DCD) kidney transplant recipients.
This study will also compare the clinical outcome within 6 month post-transplant between the 2 IS treatment groups and compare the safety throughout study period between the 2 IS treatment groups.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has end-stage kidney disease who is a suitable candidate for primary DCD kidney transplantation.
- •Subject is a resident of China.
- •Subject is scheduled to undergo DCD renal allograft transplantation with compatible ABO blood type.
- •Subject has peak panel-reactive antibodies (PRA) < 10% or "Negative" test result.
- •Subject must be a recipient of a DCD kidney and receive the organ distributed by China Organ Transplant Response System only.
- •Female subject must either:
- •Be of non-childbearing potential: Postmenopausal (defined as at least 1 year without any menses for which there is no other obvious pathological or physiological cause) prior to screening, or documented surgically sterile
- •Or, if of childbearing potential: Agree not to try to become pregnant throughout the study period and have a negative blood pregnancy test at screening.
- •A sexually active male or female subject is utilizing highly effective forms of birth control starting at screening and throughout the study period if the risk of conception exists.
- •Subject agrees not to participate in another interventional study while participating in the present study from 1 month before randomization to 1 month after the last dose of investigational drug.
排除标准
- •Subject has previously received or is receiving an organ transplant other than kidney.
- •Subject is receiving double-kidney transplant.
- •Recipients of Maastricht Class I, II, and V donor organs.
- •Recipients of Maastricht Class III and IV donor organs without a full complement of intensive care unit and intraoperative records.
- •Subject has cold ischemia time of allograft > 24 hours before kidney transplantation surgery.
- •Subject has known contraindication to administration of tacrolimus (Prograf or Advagraf), or other macrolides.
- •Subject is unlikely to comply with the visits scheduled in the protocol or has a history of non-compliance.
- •Subject has evidence of active liver disease or the presence of a chronic active hepatitis B or C within 1 month prior to kidney transplant surgery.
- •Recipient or donor is seropositive for human immunodeficiency virus.
- •Subject has active systemic infection requiring the use of antimicrobial agents within 1 week prior to kidney transplant surgery.
- •Subject has current malignancy or a history of malignancy (within the past 5 years), except non- metastatic basal or squamous cell carcinoma of the skin or carcinoma in-situ of the cervix that has been treated successfully.
- •Subject has medical or psychological conditions which would preclude compliance with the study requirements.
- •Subject has any condition, including any uncontrolled disease state other than end-stage kidney disease, that constitutes an inappropriate risk or a contraindication for participation in the study, or that could interfere with the study objectives, conduction, or evaluation.
- •Female subject who breastfeed or donate ova starting at screening and throughout the study period.
- •Male subject who donate sperm starting at screening and throughout the study period.
研究组 & 干预措施
Standard Prograf group
Participants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Tacrolimus immediate-release formulation (Drug)
Standard Prograf group
Participants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Tacrolimus prolonged-release formulation (Drug)
Standard Prograf group
Participants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Induction therapy (Drug)
Standard Prograf group
Participants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Mycophenolic acid drugs (Drug)
Standard Prograf group
Participants received from day 1 tacrolimus immediate-release formulation (Prograf) 0.1 - 0.15 milligrams/kilograms/day (mg/kg/day) orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 nanograms/milliliter(ng/mL) within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Corticosteroids (Drug)
Delayed Prograf group
Participants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Tacrolimus immediate-release formulation (Drug)
Delayed Prograf group
Participants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Tacrolimus prolonged-release formulation (Drug)
Delayed Prograf group
Participants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Induction therapy (Drug)
Delayed Prograf group
Participants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Mycophenolic acid drugs (Drug)
Delayed Prograf group
Participants received from day 3 to 5 Prograf 0.1 - 0.15 mg/kg/day orally at 12-hour interval (twice daily 1 hour before meal or 2 hours after meal) for approximately 1 month. At 1 month after Kidney transplant, Prograf was converted to Advagraf on a 1:1 (mg: mg) total daily dose basis. The Advagraf was administered orally once daily in the morning, 1 hour before the breakfast; the whole blood target trough level for Advagraf was maintained as 6 - 12 ng/mL within months 2 to 3, and 6 - 8 ng/mL within months 4 to 6.
干预措施: Corticosteroids (Drug)
结局指标
主要结局
Incidence of delayed graft function (DGF)
时间窗: Up to Day 7 after transplantation
DGF is defined as dialysis requirement during the first post-transplant week (7 days).
次要结局
- Subject survival(Up to Month 6 after transplantation)
- Incidence of acute rejection (AR)(Up to Month 6 after transplantation)
- Renal function assessed by serum creatinine(Up to Month 6 after transplantation)
- Renal function assessed by estimated glomerular filtration rate (eGFR)(Up to Month 6 after transplantation)
- Renal function assessed by urea nitrogen(Up to Month 6 after transplantation)
- Graft survival(Up to Month 6 after transplantation)
- Number of participants with 12-lead electrocardiograms (ECG) abnormalities and/or AEs(Up to Month 7 after transplantation)
- Safety assessed by incidence of treatment-emergent adverse events (TEAEs)(Up to Month 7 after transplantation)
- Safety assessed by incidence of serious adverse events (SAEs)(Up to Month 7 after transplantation)
- Number of participants with laboratory test abnormalities and/or AEs(Up to Month 7 after transplantation)
- Number of participants with vital sign abnormalities and/or AEs(Up to Month 7 after transplantation)