Abstract
G551D a CFTR mutation results in impaired chloride channel function in Cystic Fibrosis (CF).Ivacaftor, a CFTR potentiating agent improves FEV1 and sweat chloride(SC) but its effect on exercise is unproven.
Aims and Objectives: To evaluate exercise capacity in response to correction of the chloride channelopathy with ivacaftor.
Methods: In a placebo-controlled crossover study (EndX) of ivacaftor over 4 months with a 3 month open label extension (OLE) we performed cardiopulmonary exercise tests (CPET) at six time points on twenty patients. Primary outcome was VO2max as a percentage of baseline at EndX and OLE periods.
Results: FEV1, SC and exercise time showed a statistically significant difference versus placebo at EndX. Other parameters (VO2max) improved only after OLE.VO2 max & exercise time increased versus baseline at EndX and OLE in treated patients.FEV1 and SC also improved as expected.
| Endpoint | Placebo | Ivacaftor | Treatment Effect | P-Value |
| %ΔFEV1 | 1.3 (-3.2-5.9) | 13.0 (8.5-17.6) | 11.7 (5.3-18.1) | <0.001 |
| %Δ SC | 0.5 (-8.0-9.0) | -42.9 (-51.4--34.4) | -43.4 (-55.5--31.3) | <0.001 |
| %Δ Ex Time | 1.0 (-3.7-5.7) | 8.3 (3.4-13.2) | 7.3 (0.5-14.1) | 0.036 |
| %Δ VO2max | 5.6 (1.2-10.0) | 5.2 (0.5-9.9) | -0.4 (-6.8-6.0) | 0.89 |
End X Results
| Endpoint | End X | OLE |
| % Δ Ex Time | 8.0 (1.34-14.6)* | 12.1 (5.8-18.4)*** |
| %Δ VO2 max | 6.7 (2.7-10.8) ** | 12.6 (6.3-18.9)*** |
| %Δ Watts | 5.0 (1.4-8.6)** | 10.9 (5.6-16.3) |
P <0.05*; P<0.01**; P<0.001***
OLE Results
Conclusions: Early improvements in FEV1 and SC only improved exercise time, but prolonged treatment resulted in elevated VO2max.Results suggest other factors (likely muscular) add to cardiorespiratory improvements seen with ivacaftor treatment.
- Copyright ©ERS 2015
