Rationale, design and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS) – a large-scale cluster randomized controlled trial

Abstract Lowering sodium intake with a reduced-sodium, added potassium salt substitute has been proved to lower blood pressure levels. Whether the same strategy will also reduce the risks of vascular outcomes is uncertain and controversial. The Salt Substitute and Stroke Study (SSaSS) has been designed to test whether sodium reduction achieved with a salt substitute can reduce the risk of vascular disease. The study is a large-scale, open, cluster randomized controlled trial done in 600 villages across five provinces in China. Participants have either a history of prior stroke or an elevated risk of stroke based upon age and blood pressure level at entry. Villages were randomised in a 1:1 ratio to intervention or continued usual care. Salt substitute is provided free-of-charge to participants in villages assigned to the intervention group. Follow-up is scheduled every 6 months for 5 years and all potential endpoints are reviewed by a masked adjudication committee. The primary endpoint is fatal and non-fatal stroke and the two secondary endpoints are total major cardiovascular events and total mortality. The study has been designed to provide 90% statistical power (with two-sided alpha =0.05) to detect a 13% or greater relative risk reduction for stroke. The power estimate assumes a primary outcome event rate of 3.5% per year and a systolic blood pressure difference of 3.0 mmHg between randomized groups. Recruitment is complete and there are 21,003 participants (about 35 per village) that have been enrolled. Mean age is 65 years and 49% are female. There were 73% enrolled on the basis of a history of prior stroke. The trial is well placed to describe the effects of salt substitution on the risks of vascular disease and death and will provide important policy-relevant data.