Clinical and Laboratory Evaluation of Acute Rejection, Myocyte Growth, Repair, and Oxidative Stress Following de Novo Cardiac Transplant: A Comparison Between Tacrolimus- and Cyclosporine- Based Immunoprophylactic Regimens With MPA TDM
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 111
- 主要终点
- The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies
研究概览
简要总结
The purpose of this study is to assess the safety and efficacy of tacrolimus in de novo heart transplantation.
详细描述
Subcellular markers will be assessed in relationship to cellular acute rejection in de novo cardiac transplant recipients receiving either tacrolimus or cyclosporine as their primary immunosuppressant
Two parallel active arms.
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
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients (or their legal guardians) who are capable of understanding, and who have been fully informed of the purpose of the study and the risks of participation.
- •Patients (or their legal guardians) who have signed and dated the Informed Consent form and are willing and able to follow the study protocol.
- •Patients who are primary cadaveric heart transplant recipients.
- •Males or females from birth.
- •Female patients of child-bearing potential who have a current negative pregnancy test and agree to practice effective birth control, as judged by the investigator, while participating in the study. Prepubescent pediatric patients will not require pregnancy testing.
- •Patients able to tolerate oral medication and who do not have a gastrointestinal condition likely to affect the absorption kinetics or metabolism of the oral study medications.
排除标准
- •Previous organ transplant recipients.
- •Multi-organ transplant recipients.
- •Recipients of a heart from a donor with incompatible ABO blood type.
- •Patients with significant graft dysfunction and/or significant de novo infection(s) at time of randomization
- •Patients with known hypersensitivity to tacrolimus, cyclosporine, mycophenolate mofetil (MMF), daclizumab, prednisone, cremophor, polysorbate 80 and/or polyoxyl 60 hydrogenated castor oil (HCO-60).
- •Patients who are pregnant or lactating or planning to become pregnant prior to completion of the study.
- •Patients who have consumed an investigational product in the 30 days prior to transplantation or at any time during post-transplantation follow-up.
- •Patients receiving cholestyramine or colestipol.
- •Patients having any one of the following at enrolment:
- •History of malignancy, not chart-documented as cured or active malignancy (with exception of eradicable non-metastatic in-situ basal cell or squamous cell carcinoma).
- •Leukopenia (white cell count < 2500/cu mm).
- •Anemia (hemoglobin < 80 g/L).
- •Positive test for hepatitis B surface antigen and/or hepatitis C.
- •Historical positive test for human immunodeficiency virus (HIV).
- •Serum creatinine > 230 umol/l.
- •Continual elevation of AST and/or ALT to >= 3X the upper limit of normal.
- •Body mass index (weight in kg/height in m2) >
- •Undiagnosed diabetes mellitus as determined by 2 hour (2h) oral glucose tolerance test (OGTT) or fasting glucose test or uncontrolled diabetes mellitus at screening. In either case, the patient may be declared as no longer excluded by this criterion upon establishment of control of the diabetes through appropriate medical management.
- •Blood glucose >= 11.1 mmol/L at pre-operative assessment.
- •Patients having a significant disease, substance dependency, or disability that may prevent adherence to, or understanding of, the protocol and/or the investigator's instructions.
研究组 & 干预措施
Tacrolimus - Adult
Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Tacrolimus (Drug)
Tacrolimus - Adult
Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Mycophenolate mofetil (Drug)
Tacrolimus - Adult
Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Methylprednisolone (Drug)
Tacrolimus - Adult
Adults: 0.05 - 0.10 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Prednisone (Drug)
Cyclosporine - Adult
Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Cyclosporine (Drug)
Cyclosporine - Adult
Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Mycophenolate mofetil (Drug)
Cyclosporine - Adult
Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Methylprednisolone (Drug)
Cyclosporine - Adult
Adults: 3-5 mg/ kg/ day in 2 divided doses starting within 10 days of transplant
干预措施: Prednisone (Drug)
Tacrolimus - Pediatric
Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Tacrolimus (Drug)
Tacrolimus - Pediatric
Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Mycophenolate mofetil (Drug)
Tacrolimus - Pediatric
Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Methylprednisolone (Drug)
Tacrolimus - Pediatric
Pediatrics: 0.05 - 0.30 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Prednisone (Drug)
Cyclosporine - Pediatric
Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Cyclosporine (Drug)
Cyclosporine - Pediatric
Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Mycophenolate mofetil (Drug)
Cyclosporine - Pediatric
Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Methylprednisolone (Drug)
Cyclosporine - Pediatric
Pediatrics: 6 - 10 mg/ kg/ day in 2-3 divided doses starting within 10 days of transplant
干预措施: Prednisone (Drug)
结局指标
主要结局
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies
时间窗: 2 Weeks and 52 Weeks
The markers assessed were p-ERK ½ (phosphorylated extracellular signal-regulated kinase), p-JNK (phosphorylated jun N-terminal kinase) and p-p38 MAPK (phosphorylated mitogen-activated protein kinase). The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Change is defined as Week 52 assessment- Week 2 assessment.
The Change in the Markers of Growth, Apoptosis, Inflammation and Oxidation Measured in Endomyocardial Biopsies (Pediatric Population)
时间窗: 2 Weeks and 52 Weeks
The markers assessed were p-ERK ½, p-JNK and p-p38 MAPK. The data for each biopsy marker were expressed as a ratio of its densitometry / densitometry of glyceraldehyde-3-phosphate dehydrogenase (GAPDH). Change is defined as Week 52 assessment- Week 2 assessment.
次要结局
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: hsCRP(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: T-bars(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: E-selectin(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: MCP-1(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: s-ICAM(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Homocysteine(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: F2 Isoprostanes(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: BNP(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Osteopontin(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Cystatin-C(Pre-Transplant and 52 Weeks)
- Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria(52 Weeks)
- Changes in Circulating Markers of Inflammation and Oxidation: F2 Isoprostanes (Pediatric Population)(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation and Oxidation: hsCRP (Pediatric Population)(Pre-Transplant and 52 Weeks)
- Number of Acute Rejection Episodes by International Society of Heart and Lung Transplantation (ISHLT) Criteria (Pediatric Population)(52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: GSH/GSSG(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Troponin T(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-6(Pre-Transplant and 52 Weeks)
- Time to First Acute Rejection Episode Following de Novo Cardiac Transplant(52 Weeks)
- Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection(52 Weeks)
- Mean Cases of Acute Rejection (MCAR) Per Patient(52 Weeks)
- Number of Patients Requiring Antilymphocyte Antibodies or Steroids for Treatment of Severe Acute Rejection (Pediatric Population)(52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Fibrinogen(Pre-Transplant and 52 Weeks)
- Number of Cardiac Rejection Episodes Requiring Treatment(52 Weeks)
- Changes in Circulating Markers of Inflammation and Oxidation: Cystatin-C (Pediatric Population)(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: Nitrotyrosine(Pre-Transplant and 52 Weeks)
- Changes in Circulating Markers of Inflammation, Oxidation, Growth, Apoptosis, Differentiation and Survival: IL-18(Pre-Transplant and 52 Weeks)
- Number of Patients With Treatment Failure and Crossover for Treatment Failure(52 Weeks)
- Changes in Circulating Markers of Inflammation and Oxidation: Nitrotyrosine (Pediatric Population)(Pre-Transplant and 52 Weeks)
- Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52 (Pediatric Population)(26 Weeks and 52 Weeks)
- Number of Patients With Successful Steroid Taper or Withdrawal at Weeks 26 and 52(26 Weeks and 52 Weeks)
- Number of Patients With Treatment Failure and Crossover for Treatment Failure (Pediatric Population)(52 Weeks)
- Time to First Acute Rejection Episode Following de Novo Cardiac Transplant (Pediatric Population)(52 Weeks)
- Number of Cardiac Rejection Episodes Requiring Treatment (Pediatric Population)(52 Weeks)
- Mean Cases of Acute Rejection (MCAR) Per Patient (Pediatric Population)(52 Weeks)