De novo pulmonary and cardio-pulmonary transplantation MedDRA version: 9.1 Level: LLT Classification code 10025127 Term: Lung transplant MedDRA version: 9.1 Level: LLT Classification code 10028141 Term: Mucoviscidosis
Conditions
Interventions
Trade Name: PROGRAF
Pharmaceutical Form: Capsule*
INN or Proposed INN: TACROLIMUS
CAS Number: 104987113
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 0.5-
Trade
Sponsors
CHU de Limoges
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Males and females aged 18 years or more 2. CF and non-CF patients receiving single-lung or double-lung or heart-lung transplantation for the first time 3. Patients on oral tacrolimus and MMF (administration via a naso-gastric tube possible if necessary) 4. Patients without progressive chronic pathology jeopardizing short term patient and graft survival 5. Patients accepting to comply with at least the evaluation visits planned in the investigation center over the first year post-transplantation, including bronchoscopy with lung biopsy and BAL (D14, M1, M3, M6, M12); monthly TDM can be performed in a different hospital 6. Patients giving their free and informed written consent to participate to this study 7. Patients with a health insurance policy or registered under a health insurance program 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 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients aged less than 18 years or patients over 18 years under guardianship 2. Patients disagreeing with this research 3. Patients with a contra-indication to receiving tacrolimus or MMF 4. Patients on cyclosporine, sirolimus or everolimus 5. Patients who already benefited from a solid organ transplantation in the past (including lung or heart-lung transplantation) 6. Patients infected by Burkholderia cenocepacia (Burkholderia cepacia genomovar III) 7. Patients receiving HIV protease inhibitors (major pharmacokinetic interaction with tacrolimus) 8. Pregnant or breastfeeding women or those of child-bearing age who do not use an efficient contraceptive method 9. Drug users or patients suffering from neuro-psychiatric disorders preventing them from both proper comprehension of the protocol and reliable consent 10. Patients already participating in another clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the impact of optimized tacrolimus and MMF TDM and dose adjustment in patients receiving tacrolimus and MMF for lung or heart-lung transplantation during the three first years post-transplantation on the incidence of treatment failure (defined by the occurrence of at least one of the following events: death, graft loss, BPAR, BOS, discontinuation for more than 7 days or termination of either tacrolimus or MMF). ;Secondary Objective: 1) Evaluate the impact of optimized TDM vs. current strategies during the three first years post-transplantation on the efficacy score, the toxicity score, and the benefit/risk ratio, defined in accordance with the recommendations which will be elaborated by a consensus conference 2) Evaluate the impact of optimized TDM vs. current strategies during the three first years post-transplantation on: - the occurrence of each event constituting the primary criterion (death, graft loss, BPAR, BOS, discontinuation for more than 7 days or termination of either tacrolimus or MMF). - the severity of ARE and BOS as well as the evolution of pulmonary function (FEV1) - the incidence of treated infections - the evolution of renal function ;Primary end point(s): The primary endpoint is a composite criterion named “immunosuppressive treatment failure” defined by the occurrence of any of the following events during the study: 1) Histologically proven ARE Any ARE suspicion will be confirmed, if possible, by a bronchoscopy with TBB (transbronchial biopsy) and BAL (broncho-alveolar lavage) within 72 hours following the beginning of the episode. TBB will be analyzed on site by the histopathologist and graded following the international classification of ISHLT (International Society of Heart and Lung Transplantation). TBB and BAL will secondarily be reanalyzed by an independent group of histopathologists, blinded from the randomization group of each patient. ARE diagnosis will be retained in the following cases: • Positive TBB o | — |
Countries
France
Outcome results
None listed