A Prospective Study to Investigate Mycophenolic Acid (MPA) Exposure Through Area Under the Curve (AUC) in Renal Transplants Recipients Treated With Mycophenolate Mofetil (MMF) and After Conversion to Mycophenolate Sodium (EC-MPS)
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 100
- 试验地点
- 1
- 主要终点
- Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).
研究概览
简要总结
The purpose of this study is investigate mycophenolic acid exposure through area under the curve in renal transplants recipients treated with mycophenolate mofetil and after conversion to mycophenolate sodium.
详细描述
A growing body of evidence has shown that mycophenolate acid (MPA) exposure assessment and dosage adjustment are necessary in patients treated with mycophenolate mofetil (MMF), but there is still limited information about the dose-exposure-effect relationship of the enteric-coated mycophenolate sodium (EC-MPS) formulation that has quite different physicochemical properties (TETT et al., 2011).
Pharmacokinetically guided exposure-controlled area under the concentration-time curve (AUC) approaches are helpful to limit interpatient variability of MPA exposure and to improve the clinical outcome of organ transplant recipients (TETT et al., 2011).
MPA area under the concentration-time curve values between 30 and 60 μg h/mL in the early post-transplant period reduces the risk of acute rejections and seems to be appropriate in renal allograft recipients taking mycophenolate sodium (MPS) and calcineurin inhibitors (GRINYÓ et al., 2009; SOMMERER et al., 2010).
Among the benefits of therapeutic drug monitoring of MPA are the evaluation of interaction between MPA and proton pump inhibitors and association of donor-specific antibodies reduction.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Supportive Care
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years at the time of screening;
- •Subjects above the sixth month post renal transplant;
- •Subjects receiving mycophenolate mofetil;
- •Women of childbearing potential (CBP) with a negative pregnancy test at screening (urine or serum);
- •Women of CBP and men with sexual partners of CBP must agree to use a medically acceptable method of contraception throughout the study.
排除标准
- •Subjects who, in the opinion of the investigator, are not able to complete the study;
- •Recipients of multiple organ transplant (i.e., prior or concurrent transplantation of a non-renal allograft;
- •Use of any investigational drug or treatment up to 4 weeks before enrollment;
- •Subjects with a calculated GFR < 30ml/min (abbreviated MDRD formula);
- •Subjects with a screening total white blood cell count (WBC) ≤ 2000/mm3, hemoglobin ≤ 10g/dL and platelet count ≤ 100000/mm3;
- •TGO/AST, TGP/ALT and bilirubin with values three times higher that reference values;
- •History of malignancy within 3 years enrollment other than adequately treated basal cell or squamous cell carcinoma of the skin;
- •Subjects who are known to be human immunodeficiency virus (HIV), hepatitis B or hepatitis C;
- •Chronic hepatic failure;
- •Planned treatment with immunosuppressive therapies other than those described in the protocol;
- •Recipients who required desensitization protocols.
研究组 & 干预措施
Mycophenolate sodium
Arm1(Conversion):MPA AUC below 30mcg*h ml-1 - MPS+Calcineurin inhibitor+prednisone
干预措施: Mycophenolate sodium (Drug)
Mycophenolate mofetil
Arm2(Maintained):MPA AUC between 30 to 60 mg*h ml-1 or above 60 mg - MMF+Calcineurin inhibitor+prednisone
干预措施: Mycophenolate mofetil (Drug)
结局指标
主要结局
Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg*h ml-1).
时间窗: Baseline
Evaluate the frequency of renal transplants recipients taking mycophenolate mofetil (MMF) with MPA AUC below target level (30mcg\*h ml-1).
次要结局
- Evaluate the interaction between MMF or EC-MPS and the proton pump inhibitor omeprazole through the AUC in patients with MPA below target level (30mcg*h ml-1).(6 months)
- Evaluate the MPA_AUC in renal transplant patients converted to mycophenolate sodium (MPS) with equivalent dose of mycophenolate mofetil (MMF).(Baseline, five days after day one, fourteen days after day one, months 2,4 and 6)
- Evaluate the MPA_AUC in renal transplant patients maintained with mycophenolate mofetil (MMF).(baseline, months 2,4 and 6)
- Evaluate the association of MPA AUC in renal transplant recipients with donor specific antibodies (DSA);(Baseline; month 6.)
- Evaluate the association of MPA AUC with renal function estimated by MDRD formula.(Baseline; day one; months 2, 4 and 6.)
研究者
Valter Duro Garcia
PHYSICIAN NEPHROLOGY
Irmandade Santa Casa de Misericórdia de Porto Alegre