A randomized controlled trial of liposomal cyclosporine A for inhalation in the prevention of bronchiolitis obliterans syndrome following lung transplantation.

Abstract

Long-term survival after lung transplantation is limited by chronic allograft dysfunction. The aim of this study was to investigate the effect of locally augmented immunosuppression with liposomal cyclosporine A for inhalation (L-CsA-i) for the prevention of bronchiolitis obliterans syndrome (BOS). In a randomized, double-blind, placebo-controlled, multi-center Phase 3 study, 180 LT recipients in BOS grade 0 were planned to receive L-CsA-i or placebo in addition to triple-drug immunosuppression. L-CsA-i was administered twice daily via an Investigational eFlow nebulizer to recipients of single (SLT) and bilateral lung transplants (BLT) within 6-32 weeks posttransplant, and continued for 2 years. The primary endpoint was BOS-free survival. 130 patients were enrolled before the study was prematurely terminated for business reasons. Despite a 2-year actuarial difference in BOS-free survival of 14.1% in favor of L-CsA-i in the overall study population, the primary endpoint was not met (p = .243). The pre-defined per protocol analysis of SLT recipients (n = 24) resulted in a treatment difference of 58.2% (p = .053). No difference was observed in the BLT (n = 48) subpopulation (p = .973). L-CsA-i inhalation was well tolerated. Although this study failed to meet its primary endpoint, the results warrant additional investigation of L-CsA-i in lung transplant recipients.

• Authors: Claus Neurohr, Nikolaus Kneidinger, Alessandro Ghiani, Víctor Monforte, Christiane Knoop, Peter Jaksch, Jasvir Parmar, Piedad Ussetti, Amparo Sole, Joachim Müller-Quernheim, Romain Kessler, Hubert Wirtz, Gerhard Boerner, Oliver Denk, Stefanie Prante Fernandes, Juergen Behr
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 22 Issue 1 Pg. 222-229 (01 2022) ISSN: 1600-6143 [Electronic] United States
• PMID: 34587371 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. American Journal of Transplantation published by Wiley Periodicals LLC on behalf of The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Cyclosporine

Topics

• Administration, Inhalation
• Bronchiolitis Obliterans (drug therapy, etiology, prevention & control)
• Cyclosporine (therapeutic use)
• Humans
• Lung
• Lung Transplantation (adverse effects)