OSAKA: A multicenter, four arm, randomized, open label clinical studyinvestigating optimized dosing in a Prograf®/Advagraf®-basedimmunosuppressive regimen in kidney transplant subjects.Short Title: OSAKA Study(Optimizing ImmunoSuppression After Kidney Transplantation WithAdvagraf)ISN: PMR-EC-1210Transplantation with ADVAGRAF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 1,200
研究概览
简要总结
Abstract Background: The once-daily (QD), prolonged-release formulation of tacrolimus has been shown to improve adherence versus twice-daily (BD) tacrolimus. Treatment nonadherence in transplant recipients has been associated with poor graft outcomes. Methods: This open-label, parallel-group study randomized adults with end-stage renal disease undergoing primary kidney transplantation or retransplantation to an initial dose of tacrolimus BD 0.2 mg/kg per day (Arm 1; n=309), QD 0.2 mg/kg per day (Arm 2; n=302), QD 0.3 mg/kg per day (Arm 3; n=304) all with mycophenolate mofetil and corticosteroids (tapered) over 24 weeks, or tacrolimus QD 0.2 mg/kg per day with mycophenolate mofetil, basiliximab, and corticosteroids given only perioperatively (Arm 4; n=283). The primary composite endpoint (efficacy failure; per protocol set) was defined as graft loss, biopsy-confirmed acute rejection, or graft dysfunction at week 24. Graft dysfunction was defined as estimated glomerular filtration rate Modification of Diet in Renal Disease-4 formula of less than 40 mL/min/1.73 m(2). The prespecified noninferiority margin was 12.5%. Results: The per protocol set included 976 patients: 237, 263, 246, and 230 patients in Arms 1 to 4, respectively. Noninferiority of the composite endpoint was demonstrated for Arm 2 versus Arm 1; Kaplan-Meier estimates of efficacy failure were 42.2% and 40.6%, respectively (difference, -1.6%; 95% confidence interval [CI], -12.2% to 9.0%). Noninferiority to Arm 1 was not confirmed for Arm 3 (difference, -3.5%; 95% CI, -13.6% to 6.6%) or Arm 4 (difference, -7.1%; 95% CI, -16.1% to 1.9%). Graft dysfunction (estimated glomerular filtration rate <40 mL/min/1.73 m(2)) was the main determinant of composite-endpoint efficacy failure across all arms. Conclusions: In patients representative of the European kidney transplant population, tacrolimus QD-based immunosuppression (0.2 mg/kg/day), without induction, showed similar efficacy to 0.2 mg/kg per day tacrolimus BD. Trial registration: ClinicalTrials.gov NCT00717470.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized controlled study
- 盲法
- Open (masking not used)
入排标准
- 年龄范围
- 18 Years 至 one（—）
- 性别
- All
入选标准
- •Subject is eligible for the study if all of the following apply:
- •1. Age >= 18 years.
- •2. End stage kidney disease and a suitable candidate for primary renal transplantation or
- •re-transplantation (unless the graft was lost from rejection within 12 month).
- •3. Receiving a kidney transplant from a cadaveric or living (non HLA identical) donor
- •with compatible ABO blood type.
- •4. Female subject of childbearing potential must have a negative serum pregnancy test at
- •enrollment and must agree to maintain effective birth control during the study.
- •5. Capable of understanding the purpose and risks of the study, fully informed and given
- •written informed consent (signed Informed Consent has been obtained).
排除标准
- •Subject will be excluded from participation if any of the following apply:
- •1. Receiving or having previously received an organ transplant other than a kidney.
- •2. Cold ischemia time of the donor kidney > 30 hours.
- •3. Receiving a graft from a non-heart-beating donor other than of Maastricht category 3
- •(withdrawn of support awaiting cardiac arrest).
- •4. Significant liver disease, defined as having continuously elevated SGPT/ALT and/or
- •SGOT/AST and/or total bilirubin levels >= 2 times the upper value of the normal range
- •of the investigational site or is receiving a graft from a hepatitis C or B positive donor.
- •5. Requiring initial sequential or parallel therapy with immunosuppressive antibody
- •preparation(s).
- •6. Requiring ongoing dosing with a systemic immunosuppressive drug prior to
- •transplantation.
- •7. Significant, uncontrolled concomitant infections and/or severe diarrhea, vomiting,
- •active upper gastro-intestinal tract malabsorption or active peptic ulcer.
- •8. Pregnant woman or breast-feeding mother.
- •9. Subject or donor known to be HIV positive.
- •10. Known allergy or intolerance to tacrolimus, macrolide antibiotics, corticosteroids,
- •basiliximab or mycophenolate mofetil or any of the product excipients.
- •11. Diagnosis of new-onset malignancy prior to transplantation, with the exception of
- •basocellular or squamous cell carcinoma of the skin which had been treated
- •successfully.
- •12. Currently participating in another clinical trial, and/or has taken an investigational drug
- •within 28 days prior to enrollment.
- •13. Any form of substance abuse, psychiatric disorder or condition which, in the opinion of
- •the investigator, may complicate communication with the investigator.
- •14. Unlikely to comply with the visits scheduled in the protocol.