Transplant Trial Watch

A randomised single-centre trial of inhaled liposomal cyclosporine for bronchiolitis obliterans syndrome post-lung transplantation.

Iacono, A., Wijesinha, M. et al. (2019).

Erj Open Research 5(4).

This study aimed to investigate the effects of inhaled liposomal cyclosporine (L-CsA) to prevent bronchiolitis obliterans syndrome (BOS) following lung transplantation.

Patients with BOS were assigned to either receive L-CsA, twice daily at doses of 5mg or 10mg for 24 weeks with standard-of-care (SOC) oral immunosuppression, tacrolimus (0.06 mg·kg−1·day−1), mycophenolate mofetil (2000 mg·day−1) and prednisone (10–20 mg·day−1) (L-CsA group) or SOC (SOC-alone group).

21 recipients of a single or bilateral pulmonary allograft, ≥18 years of age who were clinically diagnosed BOS grade 1 or 2 and receiving tacrolimus-based immunosuppression.

There were two primary end-points being measured: 1) a composite of BOS progression-free survival, defined as time from randomisation to ≥20% decline in FEV1, re-transplantation or death (prolonged mechanical ventilation and irreversible respiratory failure equivalent to ≥20% decline of FEV1), and 2) BOS grade progression by grade changes from randomisation to study completion. A decline in FEV1 was validated for absence of concurrent illness.

24 weeks

CET Conclusions
This is a well written report of a good quality phase II study. The study was terminated early due to lower than expected enrolment rates, including 21 patients rather than the target of 30. There was no significant difference in the primary outcome, however the absolute values indicate that in a larger study a significant effect might be seen. L-CsA seemed to stabilise FEV1 and FVC compared to standard treatment alone and improve levels of the cytokines IL-2, IL-10and IFN-gamma. There were no adverse events that required cessation of the study drug. This was an exploratory study and further trials are now needed, indeed the phase III multicentre trial using L-CsA for bronchiolitis obliterans has begun.

Jadad score

Data analysis
Strict intention-to-treat analysis

Allocation concealment

Trial registration - NCT01650545

Funding source
Not reported