Article

The 6-min walk test (6MW) as an efficacy endpoint in pulmonary arterial hypertension clinical trials: demonstration of a ceiling effect.

Baylor College of Medicine, Houston, TX, United States.
Vascular Pharmacology (impact factor: 1.99). 07/2005; 43(1):36-9. DOI:10.1016/j.vph.2005.03.003 pp.36-9
Source: PubMed

ABSTRACT PAH trials traditionally use 6MW as the primary endpoint. Concerns regarding a "ceiling effect" masking efficacy have led to exclusion of patients with milder disease from most trials (BL 6MW>450 m). STRIDE I evaluated the selective endothelin A receptor antagonist, sitaxsentan (SITAX), in a 12-week randomized, double-blind, trial (178 patients) employing placebo (PBO), 100 mg or 300 mg SITAX orally once daily in PAH and included patients with NYHA class II, congenital heart disease and a BL 6MW>450 m, groups often excluded from previous trials.
We analyzed 6MW effects For All Pts (intention-to treat) and those meeting Traditional enrollment criteria, defined as patients with NYHA class III or IV and 6MW< or =450 m at BL with idiopathic PAH or PAH related to connective tissue disease. The 100 mg and 300 mg SITAX arms are pooled based on similar treatment effects on 6MW.
Existence of a "ceiling effect" is supported by these data. The magnitude of the treatment effect and statistical power when using 6MW as the endpoint. Comparisons between PAH trials that do not adjust for the effects of differing enrollment criteria require caution.

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Keywords

12-week randomized
 
300 mg SITAX arms
 
300 mg SITAX orally
 
ceiling effect
 
congenital heart disease
 
connective tissue disease
 
enrollment criteria
 
idiopathic PAH
 
masking efficacy
 
meeting Traditional enrollment criteria
 
milder disease
 
NYHA class II
 
NYHA class III
 
PAH trials
 
previous trials
 
primary endpoint
 
receptor antagonist
 
similar treatment effects
 
statistical power
 
treatment effect
 

Adaani E Frost