Peri-operative Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation
- Conditions
- Disorder Related to Lung Transplantation
- Interventions
- Drug: Ora-Plus
- Registration Number
- NCT01915082
- Lead Sponsor
- Universitaire Ziekenhuizen KU Leuven
- Brief Summary
This study investigates possible beneficial effects of peri-operative treatment (i.e. pre-transplant initiation and prompt post-transplant continuation) with azithromycin in lung transplantation. Our hypothesis is that this therapy will improve early allograft function and outcome following human lung transplantation.
- Detailed Description
After a lung transplant recipient is put on the waiting list for subsequent lung transplantation, informed consent will be sought for the current study. If signed informed is obtained, the patient will be enrolled upon admission for transplantation at which moment he/she will be randomised to placebo or azithromycin according to a blinded randomisation-list. In accordance with his/her attributed study-number, each included patient will be assigned to a pre-numbered bottle containing the study-drug, which was pre-filled and blinded for its content and are delivered in advance to the ward by the University Leuven Hospital Pharmacy. From this bottle, a first loading dose of placebo (25 mL po syrup) or azithromycin (25 mL po syrup = 1000 mg) will be given by the nurse during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of placebo (6.25 mL) or azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31) by the nurses taking care of the patient in the early post-transplant period. In case of any serious suspected drug-interactions (however very unlikely) or adverse attributable to the study drug, the study will be promptly stopped in this patient. Serious adverse events will be monitored by the treating lung transplant physicians (blinded for the study-drug) and are defined as allergic reactions including skin reactions (rash, urticaria or Stevens-Johnson syndrome), angioneurotic edema and anaphylaxis, cardiac arrhythmias (ventricular tachycardia or torsades de pointes), neurologic disorders (convulsions). Routine immunosuppressive, prophylactic and necessary antimicrobial treatment according to standardized protocol is given to all patients, independent of study drug. After transplantation, routine follow-up (e.g. biochemical and microbiological blood analyses, chest radiography, pulmonary function testing and bronchoscopic evaluation with broncho-alveolar lavage and/or trans- or endobronchial biopsies will be performed as they are currently routinely being performed as part of the standard, prospective follow-up after lung transplantation.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
- Signed informed consent
- Adult (age at least 18 years old at moment of transplantation)
- Single lung transplantation, sequential single (double) lung transplantation or heart-lung transplantation
- Known previous allergy for azithromycin (including skin reactions such as rash, urticaria or Stevens- Johnson syndrome, angioneurotic oedema and anaphylaxis)
- Retransplantation or multi-organ (other than heart-lung) transplantation
- Inclusion in Transmedics® Organ Care System (OCS™ LUNG) study (OCS-LUN-03-2010)(S53795).
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Ora-Plus Ora-Plus A first dose of placebo (25 mL po syrup) will be given during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of placebo (6.25 mL) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31). Azithromycin Azithromycin A first dose of azithromycin (25 mL po syrup = 1000 mg) will be given during preparation for subsequent lung transplantation (Day 0). After lung transplantation, 'add on' treatment of azithromycin (6.25 mL = 250 mg) syrup will be given via (naso)gastric tube or per os every other day (days 1,3,5,7,9,11,13,15,17,19,21,23,25,27,29 and 31).
- Primary Outcome Measures
Name Time Method Mean forced expiratory volume at one second (FEV1, %pred) at 3 months after lung transplantation Mean FEV1 (%pred) during the first 3 months after lung transplantation (measured at discharge; thereafter twice weekly until 8 weeks post-transplant and weekly from 8 to 12 weeks post-transplant; i.e. total estimated number of 14 spirometries per patient)
- Secondary Outcome Measures
Name Time Method Length of Intensive Care Unit (ICU) stay at 3 months after lung transplantation Length of intubation at 1 month after lung transplantation Length of hospital stay at 3 months after lung transplantation Partial Pressure of Oxygen in Arterial Blood over fraction of inspired oxygen fraction - ratio (PaO2/FiO2) at 0, 24, 48 and 72 hours after lung transplantation Primary graft dysfunction (PGD) prevalence and score at 0, 24, 48 and 72 hours after lung transplantation 6-minute walking distance at 1 month after lung transplantation Acute rejection (grade A; grade B) prevalence/severity at 1, 3 and 6 months after lung transplantation Broncho-alveolar lavage neutrophilia and cytokine/protein profile at day 1 and at 1, 3 and 6 months after lung transplantation Airway colonization at day 1 and 1, 3 and 6 months after lung transplantation Presence (i.e. growth) of Pseudomonas species or Aspergillus species in routine cultures of broncho-alveolar lavage fluid at day 1 and 1, 3 and 6 months after lung transplantation.
Plasma C-reactive protein levels at day 1, 3, 5, 7, 14 and 1, 3 and 6 months after lung transplantation Mortality at 1, 3 and 6 months after lung transplantation Ventilator-free days at 6 months after transplantation days alive and free from mechanical ventilation
Mean forced expiratory volume at one second (FEV1, %pred) at 6 months after lung transplantation Mean FEV1 (%pred) during the first 6 months after lung transplantation
Trial Locations
- Locations (1)
University Hospitals Leuven
🇧🇪Leuven, Belgium