Discontinuation versus continuation of hypertonic saline or dornase alfa
SIMPLIFY trial design and results
Design
Two parallel randomised, controlled, non-inferiority trials
Treatment
Discontinuing daily hypertonic saline, or discontinuing dornase alfa
Control
Continuing the treatment
Population
594 unique participants with cystic fibrosis taking elexacaftor-tezacaftor-ivacaftor, mean percentage predicted FEV1 96.9%
Follow-up
6 weeks
Primary endpoint
Absolute 6-week change in percentage predicted FEV1, tested for non-inferiority
Result
Discontinuing treatment was non-inferior to continuing it for the 6-week change in percentage predicted FEV1, in both the hypertonic saline trial (370 randomised) and the dornase alfa trial (477 randomised).
In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.
The trial authors, in the published abstract
How it has aged
The first serious attempt to unwind the accumulated treatment burden that VX17-445-102 made questionable. Six weeks is short and the participants had near-normal lung function, so this is permission to deprescribe in well patients rather than proof of long-term safety.
Publications
Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials
Mayer-Hamblett N, Ratjen F, Russell R, et al. Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials. Lancet Respir Med 2023 Apr;11(4):329-340.
Stopping hypertonic saline was non-inferior to continuing it over 6 weeks
Stopping dornase alfa was likewise non-inferior
Participants had well-preserved lung function and were on triple modulator therapy