Recipients of primary bilateral lung transplant allograft
Conditions
Interventions
Trade Name: Advagraf (tacrolimus)
Pharmaceutical Form: Capsule
Trade Name: Sandimmun Neoral (cyklosporine A)
Pharmaceutical Form: Capsule
Sponsors
Transplantationscntrum, Sahlgrenska Universitetssjukhuset
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Male or female lung recipients 18-70 years of age undergoing primary double (including size reduction) lung Transplantation (LTx). 2. Patient willing and capable of giving written informed consent for study participation and anticipated to be able to participate in the study for 36 months. 3. Patient that is suitable to receive induction therapy with ATG (Thymoglobulin®). Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 242 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Recipient of multi-organ transplants or previously transplanted organs. 2. Patients with donor greater than 75 years. 3. Donor lung cold ischemic time > 12 hours. 4. Patients who are recipients of ABO incompatible transplants. 5. Patients with platelet count < 50,000/mm3 at the evaluation before transplantation. 6. Patient who have received an unlicensed drug or therapy within one month prior to study entry or if such therapy is to be instituted post-transplant. 7. Patients with hypersensitivity to, or other reasons to not be able to take the immunosuppressive drugs used in the study. 8. Patients who previously have been treated with anti-thymocyte globuline preparations (e.g. ATG-Fresenius®, Thymoglobulin®). 9. Patient unable to participate in the study for the full 36-month period. 10. Patients with any past (within the past 3-5 years) or present malignancy (other than excised basal cell carcinoma). 11. Females capable of becoming pregnant must have a negative pregnancy test prior to randomization and are recomended to practice a medically approved method of birth control for the duration of the study and a period of 8 weeks following discontinuation of study medication, even where there has been a history of infertility. 12. Patients who are unlikely to comply with the study requirements. 13. Patients, and/or those receiving organs from donors, who are positive for HIV, Hepatitis B surface antigen or Hepatitis C virus.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To study the cumulative incidence of Chronic Lung Allograft Dysfunction (CLAD) (including both Bronchioloitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS), as defined by the ISHLT-criteria, Appendix II) at 36 months after lung transplantation (LTx). ;Secondary Objective: To compare the efficacy between treatment regimes by assessing the difference in mGFR, at 3 months. The cumulative incidence of PGD at 72 hours. Patient survival at 1 and 3 year. The cumulative incidence of AR and CLAD at 6 months, 1 and 3 year. Number of rejections. The cumulative incidence of BOS and RAS at 6 months, 1 and 3 year. The composite measure of freedom from AR, CLAD, graft survival, and patient survival at 12, 24 and 36 months. Development of donor specific antibodies (DSA) at 12, 24 and 36 months, according to specific protocol. Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance, at 12, 24 and 36 months. Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different formulas, at 3, 12, 24 and 36 months. ;Primary end point(s): Cumulative incidence of Chronic Lung Allograft Dysfunction (CLAD) (including both Bronchioloitis Obliterans Syndrome (BOS) and Restrictive Allograft Syndrome (RAS), as defined by the ISHLT-criteria, Appendix II) at 36 months after lung transplantation (LTx). ;Timepoint(s) of evaluation of this end point: After 3 years of treatment with study drug. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance at 3 months. 2. The cumulative incidence of primary graft dysfunction (PGD) at 72 hours. 3. Patient survival at 1 and 3 year. 4. The cumulative incidence of acute allograft rejection (AR) and CLAD at 6 months, 1 and 3 year. 5. Determined by clinical criteria, computed tomography (CT) and trans bronchial lung biopsy with broncho-alveolar lavage (BAL). 6. Number of rejections (cellular and antibody mediated), stratified by biopsy and non-biopsy verified rejections. 7. The cumulative incidence of BOS and RAS at 6 months, 1 and 3 year. 8. The composite measure of freedom from AR, CLAD, graft survival, and patient survival at 12, 24 and 36 months after transplantation. The diagnosis of AR will be based on either clinical signs or histological biopsy confirmation using the ISHLT Working Classification of Lung Transplant Pathology. 9. Development of donor specific antibodies (DSA) at 12, 24 and 36 months, according to specific protocol. 10. Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance, at 12, 24 and 36 months. 11. Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different formulas, at 3, 12, 24 and 36 months. 12. The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) at 6, 12, 24 and 36 months after transplantation as defined below; o Cumulative incidence of: ? =2 Fasting Plasma Glucose (FPG) =7,0 mmol/L = 30 consecutive days apart. ? Oral hypoglycaemic treatment =30 consecutive days. ? Insulin =30 consecutive days. ? HgbA1c =6.5% (according to American Diabetes Association – ADA) ? Symptoms of Diabetes and Random Plasma Glucose (RPG) = 11.1 mmol/L. ? 2-hour Plasma Glucose (2-hPG) = 11.1 mmol/L during an oral glucose tolerance test (OGTT). 13. Use of antidiabetic medication at 6, 12, 24 and 36 months. 14. Incidenc | — |
Countries
Denmark, Finland, Sweden
Contacts
Public ContactDennis Lindholm
Gothia Forum
Outcome results
None listed