Clinical trial NCT01915082: Peri-operative Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation
Official title: A Prospective, Randomized, Placebo-controlled Trial of Pre-transplant and Prompt Post-transplant Treatment With Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Disorder Related to Lung Transplantation
Keywords: Lung Function
Allograft Outcome
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: Fund for Scientific Research, Flanders, Belgium
name: KU Leuven
First posted: 2013-08-02
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

Eligibility 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)
* Retransplantation or multi-organ (other than heart-lung) transplantation
* Inclusion in Transmedics® Organ Care System (OCS™ LUNG) study (OCS-LUN-03-2010)(S53795).

Primary outcomes:
measure: Mean forced expiratory volume at one second (FEV1, %pred)
timeFrame: at 3 months after lung transplantation
Secondary outcomes:
measure: Length of intubation
timeFrame: at 1 month after lung transplantation
measure: Length of Intensive Care Unit (ICU) stay
timeFrame: at 3 months after lung transplantation
measure: Length of hospital stay
timeFrame: at 3 months after lung transplantation
measure: Partial Pressure of Oxygen in Arterial Blood over fraction of inspired oxygen fraction - ratio (PaO2/FiO2)
timeFrame: at 0, 24, 48 and 72 hours after lung transplantation
measure: Primary graft dysfunction (PGD) prevalence and score
timeFrame: at 0, 24, 48 and 72 hours after lung transplantation
measure: 6-minute walking distance
timeFrame: at 1 month after lung transplantation
measure: Acute rejection (grade A; grade B) prevalence/severity
timeFrame: at 1, 3 and 6 months after lung transplantation
measure: Broncho-alveolar lavage neutrophilia and cytokine/protein profile
timeFrame: at day 1 and at 1, 3 and 6 months after lung transplantation
measure: Airway colonization
timeFrame: at day 1 and 1, 3 and 6 months after lung transplantation
measure: Plasma C-reactive protein levels
timeFrame: at day 1, 3, 5, 7, 14 and 1, 3 and 6 months after lung transplantation
measure: Mortality
timeFrame: at 1, 3 and 6 months after lung transplantation
measure: Ventilator-free days
timeFrame: at 6 months after transplantation
measure: Mean forced expiratory volume at one second (FEV1, %pred)
timeFrame: at 6 months after lung transplantation
Other outcomes:
measure: Chronic lung allograft dysfunction
timeFrame: at 1 and 2 years after lung transplantation
measure: Intra-operative respiratory and hemodynamic parameters
timeFrame: at day 1 after lung transplantation
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
Study officials:
affiliation: UZ and KULeuven
name: Robin Vos, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Van Herck A, Frick AE, Schaevers V, Vranckx A, Verbeken EK, Vanaudenaerde BM, Sacreas A, Heigl T, Neyrinck AP, Van Raemdonck D, Dupont LJ, Yserbyt J, Verleden SE, Verleden GM, Vos R. Azithromycin and early allograft function after lung transplantation: A randomized, controlled trial. J Heart Lung Transplant. 2019 Mar;38(3):252-259. doi: 10.1016/j.healun.2018.12.006. Epub 2018 Dec 14.