Peri-operative Azithromycin to Improve Early Allograft Function and Outcome After Lung Transplantation

Disorder Related to Lung Transplantation Clinical Trial

— AZI003  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01915082
• Other study ID #: AZI003
• Secondary ID: 2012-003331-32
• Status: Completed
• Phase: Phase 4
• First received: July 4, 2013
• Last updated: November 10, 2015
• Start date: September 2013

Study information

• Verified date: September 2013
• Source: Universitaire Ziekenhuizen Leuven
• Contact: n/a
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 70
• Est. primary completion date: October 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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).

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Disorder Related to Lung Transplantation

Intervention

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).
• 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).

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven

Sponsors (3)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven	Fund for Scientific Research, Flanders, Belgium, Katholieke Universiteit Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Chronic lung allograft dysfunction		at 1 and 2 years after lung transplantation	No
Other	Intra-operative respiratory and hemodynamic parameters	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.	at day 1 after lung transplantation	No
Primary	Mean forced expiratory volume at one second (FEV1, %pred)	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)	at 3 months after lung transplantation	No
Secondary	Length of intubation		at 1 month after lung transplantation	No
Secondary	Length of Intensive Care Unit (ICU) stay		at 3 months after lung transplantation	No
Secondary	Length of hospital stay		at 3 months after lung transplantation	No
Secondary	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	No
Secondary	Primary graft dysfunction (PGD) prevalence and score		at 0, 24, 48 and 72 hours after lung transplantation	No
Secondary	6-minute walking distance		at 1 month after lung transplantation	No
Secondary	Acute rejection (grade A; grade B) prevalence/severity		at 1, 3 and 6 months after lung transplantation	No
Secondary	Broncho-alveolar lavage neutrophilia and cytokine/protein profile		at day 1 and at 1, 3 and 6 months after lung transplantation	No
Secondary	Airway colonization	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.	at day 1 and 1, 3 and 6 months after lung transplantation	No
Secondary	Plasma C-reactive protein levels		at day 1, 3, 5, 7, 14 and 1, 3 and 6 months after lung transplantation	No
Secondary	Mortality		at 1, 3 and 6 months after lung transplantation	No
Secondary	Ventilator-free days	days alive and free from mechanical ventilation	at 6 months after transplantation	No
Secondary	Mean forced expiratory volume at one second (FEV1, %pred)	Mean FEV1 (%pred) during the first 6 months after lung transplantation	at 6 months after lung transplantation	No