Rationale and study design of OUTSTEP-HF: a randomised controlled study to assess the effect of sacubitril/valsartan and enalapril on physical activity measured by accelerometry in patients with heart failure with reduced ejection fraction

Abstract

AIM: In PARADIGM-HF, sacubitril/valsartan demonstrated superiority to enalapril in reducing mortality and morbidity in patients with heart failure (HF) with reduced ejection fraction (HFrEF). Several patient-centred outcomes like improved physical activity and quality of life have been emphasised as important treatment goals in HF management. OUTSTEP-HF has been designed to evaluate the effect of sacubitril/valsartan compared with enalapril on non-sedentary daytime physical activity in patients with HFrEF. METHODS: OUTSTEP-HF is a randomised, actively controlled, double-blind, double-dummy study that plans to enrol 600 ambulatory patients with symptomatic HFrEF in 19 European countries. Patients will be randomised 1:1 to receive sacubitril/valsartan 97/103 mg bid or enalapril 10 mg bid. The primary objective of the study is to assess changes from baseline (Week 0) to Week 12 in exercise capacity measured by the 6-min walk test and in daily non-sedentary daytime activity. Physical activity and objective sleep parameters will be measured by accelerometry using a wrist-worn device, worn continuously from screening (Week -2) until the end of study (Week 12). As a co-primary outcome, changes from baseline in sub-maximal exercise capacity will be assessed by the 6-min walk test. Patient- and physician-reported questionnaires will be used to assess quality of life, changes in signs and symptoms of HF and sleep parameters. CONCLUSION: OUTSTEP-HF will be the largest randomised trial in HF to date to use non-invasive accelerometry to assess whether treatment with sacubitril/valsartan improves patients' daily physical activity and exercise capacity compared with enalapril.