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

NCT ID: NCT01915082

Last Updated: 2015-11-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-09-30

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.

Conditions

Disorder Related to Lung Transplantation

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

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).

Group Type: EXPERIMENTAL

Azithromycin

Intervention Type: DRUG

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

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).

Group Type: PLACEBO_COMPARATOR

Ora-Plus

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: 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).

Intervention Type: DRUG

Other Intervention Names

Zithromax®; Ora-Plus®

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).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fund for Scientific Research, Flanders, Belgium

OTHER

Sponsor Role: collaborator

KU Leuven

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Robin Vos, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UZ and KULeuven

Locations

University Hospitals Leuven

Leuven, , Belgium

Countries

Belgium

References

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.

Reference Type: DERIVED

PMID: 30686699 (View on PubMed)

Other Identifiers

2012-003331-32

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

AZI003

Identifier Type: -

Identifier Source: org_study_id