Six-Minute-Walk Test in Chronic Obstructive Pulmonary Disease Minimal Clinically Important Difference for Death or Hospitalization on behalf of the Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) Study Investigators

Rationale: Outcomes other than spirometry are required to assess nonbronchodilator therapies for chronicobstructive pulmonary dis-ease.Estimates oftheminimalclinicallyimportant differencefor the 6-minute-walk distance (6MWD) have been derived from narrow cohorts using nonblinded intervention. Objectives: To determine minimum clinically important difference for change in 6MWD over 1 year as a function of mortality and first hospitalization in an observational cohort of patients with COPD. Methods:DatafromtheECLIPSEcohortwereused(n ¼ 2,112).Deathor firsthospitalizationwereindexevents;wemeasuredchangein6MWDin the 12-month period before the event and related change in 6MWD to lungfunctionandSt.George’sRespiratoryQuestionnaire(healthstatus). Measurement and Main Results: Of subjects with change in the 6MWD data, 94 died, and 323 were hospitalized. 6MWD fell by 29.7 m (SD, 82.9 m) more among those who died than among survivors (P , 0.001). A reduction in distance of more than 30 m con-ferredahazardratioof1.93(95%confidenceinterval,1.29–2.90;P ¼ 0.001) for death. No significant difference was observed for first hospitalization.Weakrelationshipsonlywereobservedwithchange in lung function or health status. Conclusions: A reduction in the 6MWD of 30 m or more is associated withincreasedriskofdeathbutnothospitalizationduetoexacerbation in patientswith chronic obstructivepulmonary diseaseandrepresents a clinically significant minimally important difference.