NCT00895583已完成4 期
Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- Pfizer
- 入组人数
- 254
- 试验地点
- 1
- 主要终点
- Percentage of Participants With Improvement of Greater Than or Equal to [≥]5 Milliliters Per Minute Per 1.73 Square Meters (mL/Min/m^2) in Calculated Glomerular Filtration Rate (GFR) at 24 Months Post-Transplantation (On-Therapy Analysis)
研究概览
简要总结
This study will look at the effect on long-term kidney function using tacrolimus right after a transplant and then switching to sirolimus at 3 to 5 months after the transplant.
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
- •At Screening:
- •Male or female subjects aged 18 years or older.
- •Recipients who are 14 days prior to transplantation up through 14 days after transplantation.
- •Recipients of a primary, living- or deceased-donor renal allograft.
- •All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 3 months after the last dose of test article. A subject is biologically capable of having children even if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.
- •At Randomization:
- •Ninety (90) to 150 days post-transplantation.
- •Treatment with tacrolimus and an inosine monophosphate dehydrogenase (IMPDH) inhibitor initiated less than or equal to 30 days of transplantation and has remained on both for the 30 days prior to randomization.
排除标准
- •At Screening:
- •Recipients of multiple organ transplants (i.e., any prior or concurrent transplantation of any organs including prior renal transplant. )
- •Recipients of adult or pediatric en bloc kidney transplants.
- •Recipients who required or will require desensitization protocols.
- •Known history of focal segmental glomerulosclerosis (FSGS) or membranoproliferative glomerulonephritis (MPGN).
- •Evidence of active systemic or localized major infection, as determined by the investigator.
- •Received any investigational drugs or devices less than or equal to 30 days prior to transplantation.
- •Known or suspected allergy to sirolimus (SRL), tacrolimus (TAC), inosine-monophosphate dehydrogenase (IMPDH) inhibitor, macrolide antibiotics, iothalamate, iodine, iodine-containing products, including contrast media other compounds related to these products/classes of medication, or shellfish.
- •History of malignancy less than or equal to 3 years of screening (except for adequately treated basal cell or squamous cell carcinoma of the skin).
- •Recipients who are known to be human immunodeficiency virus (HIV) positive.
- •Women who are biologically capable of having children with a positive urine or serum pregnancy test at screening.
- •Breastfeeding women.
- •At Randomization:
- •Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study, or could preclude the evaluation of the subject's response.
- •Planned treatment with immunosuppressive therapies other than those described in the protocol.
- •Subjects who underwent corticosteroids withdrawal or avoidance and did not receive antibody induction at the time of transplantation with anti-thymocyte globulin (rabbit) (rATG) (Thymoglobulin®), anti-thymocyte globulin (equine) (Atgam®), or alemtuzumab (Campath®).
- •Subjects who have had corticosteroid (CS) discontinued less than or equal to 30 days before randomization.
- •Calculated glomerular filtration rate (GFR) less than 40 mL/min/1.73m2 using the simplified Modification of Diet in Renal Disease (MDRD) formula less than or equal to 2 weeks prior to randomization.
- •Spot urine protein to creatinine ratio (UPr/Cr) greater than or equal to 0.5 less than or equal to 2 weeks prior to randomization.
- •Banff (2007) grade 2 or higher acute T-cell-mediated or any acute antibody-mediated rejection at any time post-transplantation.
- •Any acute rejection (biopsy-confirmed or presumed) less than or equal to 30 days before randomization.
- •More than 1 episode of acute rejection (biopsy-confirmed or presumed).
- •Known Banff (2007) interstitial fibrosis and tubular atrophy (IF/TA) greater than or equal to grade 2 or recurrent/de novo glomerular disease.
- •Major surgery less than or equal to 2 weeks prior to randomization.
- •Active post-operative complication, e.g. infection, delayed wound healing.
- •Total white blood cell count less than 2,000/mm3 or absolute neutrophil count (ANC) less than 1000 or platelet count less than 100,000/mm3 less than or equal to 2 weeks prior to randomization.
- •Fasting triglycerides greater than 400 mg/dL (greater than 4.5 mmol/L) or fasting total cholesterol greater than 300 mg/dL (greater than 7.8 mmol/L) less than or equal to 2 weeks prior to randomization regardless of whether or not on lipid-lowering therapy.
- •Women who are biologically capable of having children with a positive urine or serum pregnancy test at randomization.
- •Breastfeeding women.
研究组 & 干预措施
Group I - Planned transition to sirolimus from tacrolimus
Experimental
干预措施: Tacrolimus (Drug)
Group I - Planned transition to sirolimus from tacrolimus
Experimental
干预措施: Sirolimus (Drug)
Group II - Continuation of tacrolimus
Active Comparator
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Percentage of Participants With Improvement of Greater Than or Equal to [≥]5 Milliliters Per Minute Per 1.73 Square Meters (mL/Min/m^2) in Calculated Glomerular Filtration Rate (GFR) at 24 Months Post-Transplantation (On-Therapy Analysis)
时间窗: Baseline, Month 24
GFR was calculated using the Modified Diet in Renal Disease (MDRD) equation using either serum creatinine traceable to isotope dilution mass spectrometry (IDMS) or serum creatinine not traceable to IDMS.
次要结局
- Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis)(Baseline, Month 12)
- Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation (Intent-to-Treat [ITT] Analysis)(Baseline, Months 12 and 24)
- Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation(Baseline, Months 12 and 24)
- Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation(Baseline, Months 12 and 24)
- Calculated GFR Using MDRD (On-Therapy Analysis)(Baseline, Months 6, 12, 18, and 24)
- Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)(Baseline, Months 6, 12, 18, and 24)
- Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)(Baseline, Month 24)
- Serum Creatinine (On-Therapy Analysis)(Baseline, Months 6, 12, 18, and 24)
- Change From Randomization in Serum Creatinine (On-Therapy Analysis)(Baseline, Months 6, 12, 18, and 24)
- Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation(Post-randomization to Month 24 post-transplantation)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])(Baseline, Month 12)
- Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization(Post-randomization to Months 12 and 24 Post-Transplantation)
- Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation(Post-Randomization to 6, 12, 18, and 24 months Post-Transplantation)
- Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months(Months 12 and 24)
- Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant(Months 6, 12, 18, and 24)
- Percentage of Participants With Antibody Use in Treatment of Acute Rejection(On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation))
- Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia(Baseline, Months 12 and 24)
- Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L])(Baseline, Months 12 and 24)
- Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)(Baseline, Months 12 and 24)
- Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)(Baseline and Months 12 and 24)
- Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use(Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation))
- Percentage of Participants With Stomatitis(From randomization up to 24 months after transplantation (On-Therapy))
- Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type(On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation))
- Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)(Baseline, Month 12)
- Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])(Baseline, Month 12)
- Percentage of Participants With New-Onset Diabetes(From Baseline to On-Therapy Month 12, from Baseline to On-Therapy Month 24, and from On-Therapy Month 12 up to On-Therapy Month 24)
- Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)(12 Months and 24 Months)
- Percentage of Participants With Infection(From randomization up to 24 months after transplantation (On-Therapy))
- Percentage of Participants With Cytomegalovirus (CMV) Infection(From randomization up to 24 months after transplantation (On-Therapy))
- Percentage of Participants With Polyomavirus Infection(From randomization up to 24 months after transplantation (On-Therapy))
- Percentage of Participants With Malignancy(From randomization up to 24 months after transplantation (On-Therapy))
研究者
研究点 (1)
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