Improvement in exercise duration, lung function and well-being in G551D-Cystic Fibrosis patients: a double-blind, placebo-controlled, randomised, cross-over study with ivacaftor.
Study design (if review, criteria of inclusion for studies)
Single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor.
Participants
Twenty G551D-CF patients.
Interventions
Ivacaftor
Outcome measures
Exercise capacity . Variables measured included percentage change from baseline (%Delta) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, BMI, sweat chloride, and disease specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %DeltaVO2max was unchanged compared to placebo as was %Deltaminute ventilation.
Main results
%Deltaexercise time (mean 7.3, CI 0.5-14,1, p=0.0222) significantly increased as did %DeltaFEV1 (11.7%, range 5.3-18.1, p<0.005) and %DeltaBMI (1.2%, range 0.1-2.3, p=0.0393) whereas sweat chloride decreased (mean -43.4; range -55.5-18.1 mmol.L-1, p<0.005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in VO2max and VE despite other positive changes including spirometric lung function and exercise time with a 28 day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort.
Authors' conclusions
Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time.