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Randomized Controlled Trial
. 2024 May;23(3):457-460.
doi: 10.1016/j.jcf.2024.02.003. Epub 2024 Feb 13.

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study

Scott H Donaldson  1 , Timothy E Corcoran  2 , Joseph M Pilewski  2 , Beth L Laube  3 , Peter Mogayzel  3 , Agathe Ceppe  4 , Jihong Wu  4 , Kirby Zeman  4 , Steven M Rowe  5 , David P Nichols  6 , Alex H Gifford  7 , William D Bennett  4 , Nicole Mayer-Hamblett  6 ; SIMPLIFY MCC Study teams  4
Affiliations
Randomized Controlled Trial

The effect of discontinuing hypertonic saline or dornase alfa on mucociliary clearance in elexacaftor/tezacaftor/ivacaftor treated people with cystic fibrosis: The SIMPLIFY-MCC Study

Scott H Donaldson et al. J Cyst Fibros. 2024 May.

Abstract

Many people with CF (pwCF) desire a reduction in inhaled treatment burden after initiation of elexacaftor/tezacaftor/ivacaftor. The randomized, open-label SIMPLIFY study showed that discontinuing hypertonic saline (HS) or dornase alfa (DA) was non-inferior to continuation of each treatment with respect to change in lung function over a 6-week period. In this SIMPLIFY substudy, we used gamma scintigraphy to determine whether discontinuation of either HS or DA was associated with deterioration in the rate of in vivo mucociliary clearance (MCC) in participants ≥12 years of age. While no significant differences in MCC endpoints were associated with HS discontinuation, significant improvement in whole and peripheral lung MCC was observed after discontinuing DA. These results suggest that pwCF on ETI with mild lung disease do not experience a subclinical deterioration in MCC that could later impact health outcomes after discontinuing HS, and in fact may benefit from improved MCC after stopping DA treatment.

Keywords: Clinical trial; Cystic fibrosis; Dornase alfa; Hypertonic saline; Mucociliary clearance; Withdrawal.

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Conflict of interest statement

Declaration of competing interest Unrelated to the submitted work, SHD reports research funding from Chiesi USA, Vertex Pharmaceuticals, Calithera Biosciences, and 4D Molecular Therapeutics, and consulting income from Boehringer Ingelheim and Abbvie. PJM reports grant funding from Vertex Pharmaceuticals and Eloxx. SMR reports grant funding from Vertex Pharmaceuticals, Galapagos/Abbvie, Eloxx, Synspira, Translate Bio, Arcturus, Astra-Zenica, and Ionis, and consulting income from Vertex Pharmaceuticals, Synspira, Renovion, Cystetic Medicines, and Arcturus; all personal conflicts to SMR were resolved or ended in 2022 or before. AHG has clinical trial agreements with AbbVie, 4D Molecular Therapeutics, and Insmed. TEC reports research funding from NIH, Astra Zeneca, Regeneron, Pieris, and the CF Foundation through a Research Development Program award. NMH reports grants from CFF, NIH, and FDA, and DSMB membership for the NIH.

Figures

Figure 1:
Figure 1:. Effect of DA discontinuation and continuation on MCC.
A. Scatter plot of baseline vs. 6-week WLAveClr90 in DA discontinuation cohort. B. Scatter plot of baseline vs. 6-week WLAveClr90 in DA continuation cohort. C. Between group comparison of the absolute change in WLAveCLr90(%)
See this image and copyright information in PMC

References

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