Clinical Study Evaluating Two Treatment Protocols for Immunosuppressive Drugs. Looking at 3-year Incidence of CLAD.
- Conditions
- AllograftsLung Transplantation
- Interventions
- Registration Number
- NCT02936505
- Lead Sponsor
- Vastra Gotaland Region
- Brief Summary
A controlled randomized, open-label, multi-centre study evaluating if an immunosuppressive protocol, based on ATG-induction, once daily tacrolimus-dose (Advagraf®), mycophenolate mofetil and corticosteroid reduces the incidence of chronic lung allograft dysfunction (CLAD) after lung transplantation, in comparison with a standard cyclosporin-based protocol.
- Detailed Description
Study purpose:
To evaluate whether the use of a once-daily tacrolimus-dose regimen (Advagraf®), based on anti-thymocyte globulin (Thymoglobulin®) induction, mycophenolate mofetil (MMF) and corticosteroids, reduces the cumulative incidence of CLAD after de novo lung transplantation at 36 months, in comparison with a twice-daily cyclosporin-based protocol, otherwise identical between groups.
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 249
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm B:Tacrolimus Corticosteroids Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids. Arm B:Tacrolimus Mycophenolate mofetil (MMF) Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids. Arm A:Cyclosporine Rabbit Anti thymocyte globulin Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label. Arm A:Cyclosporine Corticosteroids Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label. Arm A:Cyclosporine Mycophenolate mofetil (MMF) Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label. Arm B:Tacrolimus Rabbit Anti thymocyte globulin Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids. Arm A:Cyclosporine Cyclosporine Group A: Cyclosporine A, Mycophenolate mofetil (MMF) and corticosteroids according to local practice and approved label. Arm B:Tacrolimus Tacrolimus Group B: Tacrolimus (Advagraf), Mycophenolate mofetil (MMF) and corticosteroids.
- Primary Outcome Measures
Name Time Method Number of patients with incidence of CLAD 72 months is outcome for continuation study The cumulative incidence of CLAD (including both BOS and RAS, as defined by the Appendix II) at 72 months after lung transplantation.
- Secondary Outcome Measures
Name Time Method Renal function mGFR 36 months Renal function evaluated by measured glomerular filtration rate (mGFR), by Iohexol or Cr-EDTA clearance.
Patient survival 3 year Patient survival
Cumulative incidence of acute allograft rejection and CLAD 3 year The cumulative incidence of acute allograft rejection (AR) and CLAD. - Determined by clinical criteria, computed tomography (CT) and trans bronchial lung biopsy with broncho-alveolar lavage (BAL). - Number of rejections (cellular and antibody mediated), stratified by biopsy and non-biopsy verified rejections.
Proteinuria 36 months Development and magnitude of proteinuria
Lipid profile 36 months Lipid profile (Total cholesterol, LDL-cholesterol, HDL-cholesterol, Triglycerides, TSH, T4, HbA1c)
Safety and tolerability 0-36 months Safety and tolerability
Quality of life assessed by EQ5D Questionnaire 12 months Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions)
Glomerular Filtration Rate 3 months Renal function evaluated by measured glomerular filtration rate
Primary graft dysfunction 72 hours Cumulative incidence of primary graft dysfunction
Composite measure of freedom from AR, CLAD, graft and patient survival 36 months Composite measure of freedom from first event of AR, CLAD, graft survival, and patient
Incidence of primary graft dysfunction 72 hours cumulative incidence of primary graft dysfunction
Cumulative incidence of BOS and RAS 3 year The cumulative incidence of BOS and RAS
Development of donor specific antibodies 36 months Development of donor specific antibodies (DSA) according to specific protocol.
Renal function cGFR 36 months Renal function evaluated by calculated glomerular filtration rate (cGFR), by three different Formulas.
Post Transplantation Diabetes Mellitus 36 months The cumulative incidence of Post Transplantation Diabetes Mellitus (PTDM) after transplantation as defined below -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). Baseline OGTT will be performed pre-transplant.Antidiabetic medication 36 months Use of antidiabetic medication
Antihypertensive and lipid lowering drugs 36 months Incidence and number of antihypertensive and lipid lowering drug
Malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers. 36 months Cumulative incidence of malignancy stratified by post-transplant lymphoproliferative disorder (PTLD) and all other cancers.
Quality of life, assessed by St Georges Respiratory Questionnaire (SGRQ) 36 months Quality of life, the relative difference over time will be investigated after LTx. The SGRQ total score ranges from 0 to 100 where 100 indicates the worst quality of life.
Cytomegalovirus 0-36 months Incidence of Cytomegalovirus (CMV) that required treatment (CMV-infection and CMV syndrome).
Quality of life assessed by St Georges Respiratory Questionnaire (SGRQ) 12 months Quality of life, the relative difference over time will be investigated after LTx. The SGRQ total score ranges from 0 to 100 where 100 indicates the worst quality of life.
Pharmacokinetics of the Tacrolimus drug in patients in the CF sub group 6 months Define the pharmacokinetics as an AUC construction, of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.
Immunological equipotency of tacrolimus and cyclosporine A 0-36 months Immunological equipotency of tacrolimus once daily (OD) and cyclosporine A twice daily (BiD) in vivo and in vitro, according to separate protocol.
Occurrence of treatment failures 0-36 months Occurrence of treatment failures up to or at 36 months; defined as a composite endpoint of graft loss, death, loss to follow up or discontinuation due to lack of efficacy or toxicity (at least one condition must be present).
Quality of life, assessed by EQ5D Questionnaire 24 months Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions).
Quality of life, assessed by EQ5D Questionnaire (SGRQ) 36 months Quality of life, the relative difference over time will be investigated after LTx, where 5 questions are raised and answer is between 11111 (no problems) and 33333 (extreme problems in all dimensions).
Pharmacokinetics, of the Tacrolimus drug in patients in the CF sub group population week 4 Define the pharmacokinetics as an AUC construction, of Tacrolimus in non-CF patients (n=12) and all included CF patients (n=15-20) undergoing primary lung transplantation (LTx) treated with an Advagraf® based-immunosuppression.
Recovery of right heart function 0-36 months Recovery of right heart function irrespective of diagnosis in patients with pulmonary arterial hypertension (PAH, categories 1-5 according to WHO 1-5).
Trial Locations
- Locations (5)
Oslo University Hospital
🇳🇴Oslo, Norway
Rigshospitalet
🇩🇰Copenhagen, Denmark
Skåne University Hospital
🇸🇪Lund, Sweden
Helsinki University Hospital
🇫🇮Helsinki, Finland
Sahlgrenska Univ Hospital
🇸🇪Göteborg, Sweden