A Pilot Study Comparing the Safety and Efficacy of Zortress (Everolimus) With Low Dose Tacrolimus to Early Conversion to Calcineulin Inhibitor-Free Regimen and Mycophenolic Acid With Standard Dose Tacrolimus in Recipients of ECD/DCD Kidneys
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 发起方
- 入组人数
- 25
- 试验地点
- 1
- 主要终点
- Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months
研究概览
简要总结
The purpose of this pilot study is to evaluate concentration-controlled everolimus with low dose tacrolimus compared to early conversion to CNI-free regimen and MMF/MPA with standard dose tacrolimus in de novo renal transplant recipients of ECD/DCD kidneys. Given tacrolimus and MMF/MPA is a widely prescribed immunosuppressive regimen in the United States, comparisons of tacrolimus and MMF/MPA regimens to investigational therapies and treatment regimens are needed. Also, considering the fact that ECD/DCD is a fast growing fraction of donors, evaluation of various regimens' effects on rather delicate ECD/DCD kidneys is necessary.
详细描述
The purpose of this pilot study is to evaluate concentration-controlled everolimus with low dose tacrolimus compared to early conversion to CNI-free regimen and MMF/MPA with standard dose tacrolimus in de novo renal transplant recipients of ECD/DCD kidneys. Given tacrolimus and MMF/MPA is a widely prescribed immunosuppressive regimen in the United States, comparisons of tacrolimus and MMF/MPA regimens to investigational therapies and treatment regimens are needed. Also, considering the fact that ECD/DCD is a fast growing fraction of donors, evaluation of various regimens' effects on rather delicate ECD/DCD kidneys is necessary.
The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.
The key secondary objective is to compare renal function of the everolimus treatment arms to the MMF/MPA treatment arm at 12 and 24 months post-transplantation. Renal function will be measured by the calculated glomerular filtration rate (GFR), using the MDRD (Modification of Diet in Renal Disease) formula (20).
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
- •Male or female recipients 18-65 years of age undergoing primary or secondary kidney transplantation
- •Recipients of primary or secondary cadaveric, ECD/DCD kidney (defined as follows)
- •Donor whose heart has irreversibly stopped beating, previously referred to as non-heart-beating or asystolic donation
- •Brain-dead donor > 60 years old
- •Donor aged 50-59 years old with two of the following criteria:
- •History of hypertension
- •Terminal serum creatinine ≥ 1.5 mg/dL
- •Death resulting from cerebrovascular accident
- •Patients who have given written informed consent to participate in the study
排除标准
- •Cold ischemic time (CIT) > 30 hours
- •Patients who are ABO incompatible transplants, or T, or B cell crossmatch positive transplant
- •Patients with a known hypersensitivity to any of the study drugs or to drugs of similar chemical class
- •Non-controlled DCD
- •Donor age >70
- •Patients with BMI >32 at baseline before surgery
- •Pregnant or lactating females
- •Females of childbearing potential unwilling to use an effective means of contraception or are planning to become pregnant
- •Patients with platelet count <100,000/mm3 at the evaluation before randomization.
- •Patients with an absolute neutrophil count of < 1,500/mm³ at baseline before surgery or white blood cell count of < 4,500/mm³
- •Patients who are recipients of multiple solid organ transplants
- •Patients who have severe hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >5.6 mmol/L). Patients with controlled hyperlipidemia are acceptable
- •Patients who have an abnormal liver profile such as ALT, AST, Alk Phos or total bilirubin >3 times the upper normal limit
- •Patients who are treated with drugs that are strong inducers or inhibitors of cytochrome P450 3A4, such as terfenadine, astemizole, cisapride, erythromycin, azithromycin, itraconazole, rifampin or lovastatin
- •Patients who received an investigational drug or who have been treated with a non-protocol immunosuppressive drug or treatment within 30 days or 5 half-lives prior to randomization
- •Patients with a history of malignancy of any organ system, treated or untreated, within the past 2 years whether or not there is evidence of local recurrence or metastases, with the exception of localized basal cell carcinoma of the skin
- •Patients who are HIV-positive or Hepatitis C (PCR+ only) or B surface antigen positive
- •Recipients of organs from donors who test positive for Hepatitis B surface antigen or Hepatitis C (PCR+ only) are excluded
- •Patients with a history of severe diarrhea, active peptic ulcer disease, or uncontrolled diabetes mellitus (Hgb A1c <7.0 %) at baseline
- •Patients who have any surgical or medical condition, which in the opinion of the investigator, might significantly alter the absorption, distribution, metabolism and excretion of study medication, and/or the presence of severe diarrhea or active peptic ulcer
- •Patients who have cardiac failure (e.g. resting dyspnea, symptoms with less than ordinary activity, marked limitation of activity) at time of screening or any other severe cardiac disease as determined by the investigator
- •Patients with abnormal physical or laboratory findings of clinical significance within 3 months of randomization which would interfere with the objectives of the study
- •Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation therapy after transplantation (Low dose aspirin treatment is allowed)
- •Patients with known history of focal segmental glomeruloscrelosis
- •Presence of psychiatric illness (i.e., schizophrenia, bipolar, major depression) that, in the opinion of the investigator, would interfere with study requirements
研究组 & 干预措施
ERL & TAC
Concentration controlled everolimus(ERL) & Low dose tacrolimus(TAC) + corticosteroid withdraw
干预措施: Everolimus (Drug)
Standard dose TAC + MMF/MPA
Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw
干预措施: Mycophenolate mofetil (MMF/MPA) (Drug)
ERL & TAC
Concentration controlled everolimus(ERL) & Low dose tacrolimus(TAC) + corticosteroid withdraw
干预措施: Tacrolimus (Drug)
ERL & TAC --> MMF/MPA
Concentration controlled everolimus & low dose tacrolimus --> mycophenolate mofetil (MMF) at Month 3 + corticosteroid
干预措施: Everolimus (Drug)
ERL & TAC --> MMF/MPA
Concentration controlled everolimus & low dose tacrolimus --> mycophenolate mofetil (MMF) at Month 3 + corticosteroid
干预措施: Tacrolimus (Drug)
ERL & TAC --> MMF/MPA
Concentration controlled everolimus & low dose tacrolimus --> mycophenolate mofetil (MMF) at Month 3 + corticosteroid
干预措施: Mycophenolate mofetil (MMF/MPA) (Drug)
Standard dose TAC + MMF/MPA
Standard dose of tacrolimus + mycophenolate mofetil + corticosteroid withdraw
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Evaluate Concentration-controlled Everolimus and Low Dose Tacrolimus Compared to MMF/MPA With Standard Dose Tacrolimus at 24 Months
时间窗: 24 months
The primary objective of this study is to evaluate concentration-controlled everolimus and low dose tacrolimus compared to MMF/MPA with standard dose tacrolimus at 24 months post-transplant with respect to the composite efficacy failure rates (treated biopsy proven acute rejection episodes (BPAR), graft loss, death, loss to follow-up) in de novo renal transplant recipients.
次要结局
- Compare Renal Function of the Everolimus Treatment Arms to the MMF/MPA Treatment Arm at 12 and 24 Months Post-transplantation(24 months)
研究者
Matthew Cooper
Dr. Matthew Cooper
Georgetown University