AZI003: Peri-operative Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation
Study Details
Study Description
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
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.
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: 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). |
Drug: Azithromycin
Zithromax® oral suspension 200 mg/ 5 mL (Pfizer, UK):
Zithromax® 1000 mg syrup per os once at recipient intake for lung transplantation (day 0); followed by Zithromax® 250 mg syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31).
Other Names:
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| Placebo Comparator: 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). |
Drug: Ora-Plus
Ora-Plus® oral suspension (Paddock Laboratories, 3940 Quebec Avenue N, Minneapolis, MN 55427, USA; NDC-number: 0574-0303-16):
Ora-Plus® 25mL syrup per os once at recipient intake for lung transplantation (day 0); followed by Ora-Plus® 6.25 mL syrup via (naso)gastric tube or per os every other day until one month after lung transplantation (days 1,3,5,7,9,11,13,15, 17,19,21,23,25,27,29 and 31).
Other Names:
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Outcome Measures
Primary Outcome Measures
- 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
- Length of intubation [at 1 month after lung transplantation]
- Length of Intensive Care Unit (ICU) stay [at 3 months 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
Other Outcome Measures
- Chronic lung allograft dysfunction [at 1 and 2 years after lung transplantation]
- Intra-operative respiratory and hemodynamic parameters [at day 1 after lung transplantation]
Intra-operative respiratory parameters (vent. mode (PCV/VCV), Pinsp (PCV), Tidal Volume (VCV/PCV), Ppeak (VCV), Pplat (VCV), Pmean (VCV), PEEP, I:E ratio, One Lung Ventilation (Y/N), Bilateral Lung Ventilation, FiO2, PaO2, PaCO2, End-Tidal CO2, MVSO2) and hemodynamic parameters (PAP (S/D/Mean), BP (S/D/Mean), CO, Heart Rate, CVD) and use of Cardio Pulmonary Bypass or Extra Corporeal Membrane Oxygenation at T0 (after induction) and after 1, 2, 3, 4, 5, 6, 7, 8, etc. hours during transplantation and at the end of operation.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
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
Exclusion Criteria:
-
Known previous allergy for azithromycin (including skin reactions such as rash, urticaria or Stevens- Johnson syndrome, angioneurotic oedema and anaphylaxis)
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Retransplantation or multi-organ (other than heart-lung) transplantation
-
Inclusion in Transmedics® Organ Care System (OCS™ LUNG) study (OCS-LUN-03-2010)(S53795).
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | University Hospitals Leuven | Leuven | Belgium | B-3000 |
Sponsors and Collaborators
- Universitaire Ziekenhuizen Leuven
- Fund for Scientific Research, Flanders, Belgium
- KU Leuven
Investigators
- Principal Investigator: Robin Vos, MD, PhD, UZ and KULeuven
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- AZI003
- 2012-003331-32