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 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 5 provinces in China. Participants have either a history of stroke or an elevated risk of stroke based on age and blood pressure level at entry. Villages were randomized 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 6months for 5years, and all potential endpoints are reviewed by a masked adjudication committee. The primary end point is fatal and nonfatal stroke, and the 2 secondary endpoints are total major cardiovascular events and total mortality. The study has been designed to provide 90% statistical power (with 2-sided α = .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 3.0mm Hg between randomized groups. Recruitment is complete and there are 20,996 participants (about 35 per village) that have been enrolled. Mean age is 65years and 49% are female. There were 73% enrolled on the basis of a history of 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.

Effect of low-sodium salt substitutes on blood pressure, detected hypertension, stroke and mortality

“…Fourth, there was scarce data on important outcomes such as stroke or CV mortality. The ongoing salt substitute SSaSS trial features stroke as primary outcome 28. Fifth, we included RCTs with all ranges of follow-up times.…”

Estimated population wide benefits and risks in China of lowering sodium through potassium enriched salt substitution: modelling study

“…The modelled policy was a nationwide salt substitution intervention based on the Salt Substitute and Stroke Study, a large scale, cluster randomised controlled trial currently being conducted in 600 villages across five provinces in rural areas of northern China (clinicalTrials.gov NCT02092090) to estimate the effect of salt substitutes on risk of stroke 1112. The salt substitute used in the Salt Substitute and Stroke Study, manufactured according to national manufacturing standards (which requires 70±10% sodium chloride and 30±10% potassium chloride), was purchased from a local provider in each county.…”

Rationale, design, and baseline characteristics of the Salt Substitute in India Study (SSiIS): The protocol for a double‐blinded, randomized‐controlled trial

“…The salt substitute used in this study is considered generally safe, but has a potential risk of causing hyperkalemia (defined as serum potassium level more than 6.5 mmol/L) if consumed in very large quantities (more than 50 g/day) 31 . However, this risk is considered to be very low, 32,33 and concordantly, reduced‐sodium and added‐potassium products that are currently available to the general public in India does not carry specific warnings on product packaging 34 . We additionally mitigated potential adverse effects of the salt substitute by excluding participants with renal disease and concurrent use of potassium‐sparing or potassium‐supplementing medicines.…”

“…We additionally mitigated potential adverse effects of the salt substitute by excluding participants with renal disease and concurrent use of potassium‐sparing or potassium‐supplementing medicines. Aside from hyperkalemia, there were no other specific adverse effects anticipated based on prior human trials 19,32 …”