Study design (if review, criteria of inclusion for studies)
Double-blind, randomized multicenter trial.
Participants
CF subjects aged 6-21 years with a forced expiratory volume in 1 second (FEV1) >/=25% to
Interventions
Patients were randomized to receive TIP or placebo (1:1) twice daily for one treatment cycle (28.5 days on drug, 28 days off drug).
Outcome measures
The primary endpoint was relative change in forced expiratory volume in 1 second (FEV1) % predicted from baseline to Day 29. A pre-specified sensitivity analysis evaluated absolute change in FEV1 % predicted. Other endpoints included Pa sputum density and safety.
Main results
A total of 62 patients out of a target of 100 (mean age 12.9 years, baseline FEV1 59.2% predicted, Pa sputum density 7.4 log10 colony forming units [CFU]) per gram were randomized. Mean treatment differences (TIP-placebo) were 5.9% (p=0.148) and 4.4% (p<0.05) for relative and absolute change in FEV1 % predicted respectively. TIP significantly reduced Pa sputum density by -1.2 log10 CFU (p=0.002). Treatment with TIP was well tolerated.
Authors' conclusions
Relative change in FEV1 % predicted with TIP treatment was in the expected range based on the literature, but did not reach statistical significance versus placebo. Placebo control and use of treatment naive patients led to significant recruitment challenges and an underpowered study with consequent impact on the generated data. However, significant improvements in other outcomes including absolute change in FEV1 % predicted and reduction in Pa sputum density indicate that TIP is efficacious and well tolerated in CF patients.