Infinitix-BOS Trial: Multi-Center, Randomised, Double-Blind Placebo-Controlled Trial of Nintedanib in Lung Transplant Recipients with Bronchiolitis Obliterans Syndrome (BOS) Grade 0-p and Grade 1-2

IntroductionTransbronchial lung biopsy (TBLB) is frequently performed in single-lung and double-lung transplant recipients for evaluation of clinical and radiological findings as well as routine surveillance for acute cellular rejection. While rates of clinically significant TBLB-related haemorrhage are <1% for all comers, the incidence in lung transplant recipients is reported to be higher, presumably due to persistent allograft inflammation and alterations in allograft blood flow. While routinely performed by some bronchoscopists, the efficacy and safety profile of prophylactic administration of topical intrabronchial diluted epinephrine for the prevention of TBLB-related haemorrhage has not been explored in a prospective manner.Methods and analysisIn this randomised, double-blind, placebo-controlled multicentre trial (PROPHET Study), single-lung and double-lung transplant adult recipients from participating institutions who are scheduled for bronchoscopy with TBLB for clinical indications will be identified. Potential participants who meet inclusion and exclusion criteria and sign an informed consent will be randomised to receive either diluted epinephrine or placebo prior to performance of TBLB. The degree of TBLB-related haemorrhage will be graded by the performing bronchoscopist as well as independent observers. The primary analysis will compare the rates of severe and very severe bleeding in participants treated with epinephrine or placebo. The study will also evaluate the safety profile of prophylactic topical epinephrine including the occurrence of serious cardiovascular and haemodynamic adverse events. Additional secondary outcomes to be explored include rates of non-severe TBLB-related haemorrhage, overall yield of the bronchoscopic procedure and non-serious cardiovascular and haemodynamic adverse effects.Ethics and disseminationThe study procedures were reviewed and approved by institutional review boards in participating institutions. This study is being externally monitored, and a data and safety monitoring committee has been assembled to monitor patient safety and to evaluate the efficacy of the intervention. The results of this study will be published in peer-reviewed scientific journals and presented at relevant academic conferences.Trial registration numberNCT03126968; Pre-results.

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Effect of Maintenance Azithromycin on Established Bronchiolitis Obliterans Syndrome in Lung Transplant Patients

Canadian Respiratory Journal ◽

10.1155/2008/158681 ◽

2008 ◽

Vol 15 (4) ◽

pp. 199-202 ◽

Cited By ~ 20

Author(s):

Nancy R Porhownik ◽

Wael Batobara ◽

Wayne Kepron ◽

Helmut W Unruh ◽

Zoheir Bshouty

Keyword(s):

Bronchiolitis Obliterans ◽

Lung Transplant ◽

Treatment Initiation ◽

Controlled Trial ◽

Pulmonary Function Tests ◽

Bronchiolitis Obliterans Syndrome ◽

Transplant Recipients ◽

Transplant Patients ◽

Lung Transplant Recipients ◽

Mean Time

BACKGROUND: Bronchiolitis obliterans syndrome (BOS), the main cause of late mortality following lung transplantation, is defined as an irreversible decline in forced expiratory volume in 1 s (FEV1).Previous studies using azithromycin for BOS in lung transplant patients have demonstrated a potential reversibility of the decline in FEV1.OBJECTIVES: To examine whether initiating azithromycin reverses decline in FEV1in lung transplant recipients with established BOS of at least three months.METHODS: Pulmonary function tests were performed every three months in seven lung transplant recipients with established BOS of at least three months. FEV1was recorded at six and three months before initiation, at time of initiation, and three, six, nine and 12 months postazithromycin initiation. The primary end point was change in FEV1. During the study, no immunosuppressive medication changes or acute rejection episodes occurred.RESULTS: Mean time from transplant to azithromycin initiation was 64 months (range 17 to 117 months). Mean time from BOS diagnosis to azithromycin initiation was 22 months (range three to 67 months). Rate of FEV1decline from six months before azithromycin initiation, and rates of FEV1increase from initiation to three and 12 months post-treatment initiation, were not statistically significant (P=0.32, P=0.16 and P=0.18, respectively). Following a trend toward improvement in the first three months after treatment initiation, FEV1tended to stabilize.DISCUSSION: Although several studies address the possible benefit of maintenance azithromycin in lung transplant patients with BOS, the role of the drug remains unproven in these patients, and would best be addressed by a large randomized controlled trial.

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