China Salt Substitute and Stroke Study (SSaSS)

A LARGE-SCALE CLUSTER RANDOMIZED TRIAL TO DETERMINE THE EFFECTS OF SODIUM REDUCTION ON STROKE: THE CHINA SALT SUBSTITUTE AND STROKE STUDY (SSaSS)

The study is a large scale cluster randomised trial to evaluate the effects of sodium reduction based upon the use of salt substitute on the risk of stroke defined as the occurrence of stroke and stroke deaths. The corresponding null hypothesis that will be tested is that sodium reduction will have no effect upon stroke risk. The secondary objectives are to determine effects of sodium reduction on major vascular events and total mortality.

Study Overview

• Status: Completed
• Conditions: Stroke
• Intervention / Treatment: Behavioral: Dietary sodium reduction

Detailed Description

Lowering sodium intake and the use of salt substitute have been proved to lower blood pressure levels. Effects on the risks of vascular outcomes have not been defined in an adequately powered randomised trial. Rural Chinese are known to consume very large quantities of sodium and to suffer from very high rates of hypertension and stroke. This study is a large scale cluster randomised trial done in rural areas of China. The study will define the effects of a salt substitute-based sodium reduction strategy on the primary outcome of stroke. Secondary endpoints will include major cardiovascular events and total mortality. The study will be conducted in 600 rural villages across five Northern Chinese provinces and Tibet. The study will recruit 35 individuals at elevated risk of stroke from each village for a total of 21,000 participants. The participating villages will be randomised into intervention and control group with 1:1 allocation. Recruitment will prioritise individuals with a history of stroke but also include older individuals with high blood pressure. Follow up is scheduled for 5 years. Individuals in intervention villages will receive repeated dietary advice and a supply of low sodium salt substitute while individuals in control villages will receive dietary advice at baseline only. Every 6 months throughout follow-up each individual will be contacted by phone call to inquire about the occurrence of stroke, hospitalisation for any cause and diagnoses of any other serious illnesses. The interview will be structured and done by individuals masked to the randomised assignment of each individual. For all deaths identified and all events that might possibly be non-fatal strokes a home visit will be made. A series of process indicators including urinary sodium, urinary potassium, blood pressure, knowledge about sodium and use of salt substitute will also be measured on a random sample of at least 20 individuals drawn from a random selection of 60 villages at baseline and every year thereafter.

• Study Type: Interventional
• Enrollment (Actual): 20996
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Hebei
    • Shijiazhuang, Hebei, China, 71000
      • Hebei Province Centre for Disease Control and Prevention
  • Liaoning
    • Shenyang, Liaoning, China, 110001
      • China Medical Universtity
  • Ningxia
    • Yinchuan, Ningxia, China, 750004
      • Ningxia Medical University
  • Shaanxi
    • Xi'an, Shaanxi, China, 710049
      • Xi'an Jiaotong University
  • Shanxi
    • Changzhi, Shanxi, China, 046000
      • Changzhi Medical Colledge

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Disease history
• Prior stroke and/or
• Aged 60 years or over and with uncontrolled high blood pressure (systolic blood pressure >=140 millimeters of mercury (mmHg) at visit if on blood pressure lowering medication; systolic blood pressure>=160 millimeters of mercury (mmHg) if not on blood pressure lowering medication)
• Ownership of a phone by the participant or a household member

Exclusion Criteria:

• Participant or family member is using a potassium-sparing diuretic
• Participant or family member is using a potassium supplement
• Participant or family member has serious renal impairment
• Participant or family member has other reason for concern about use of salt substitute
• Participant eats most meals outside the home
• Participant is not expected to live longer than 6 months from the date of assessment as estimated by the village doctor
• Another family member living in the same household has already been included in the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control; Dietary advice at baseline only
Experimental: Dietary sodium reduction; Dietary advice and reduced-sodium added-potassium salt substitute	Behavioral: Dietary sodium reduction; Ongoing dietary advice and a supply of a reduced-sodium added-potassium salt substitute; Other Names: Reduced-sodium added-potassium salt substitute

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke	The primary outcome will be stroke defined according to standard criteria on the basis of an acute disturbance of focal neurological function and resulting in death or symptoms lasting more than 24 hours. Imaging, clinical and laboratory data will be collected wherever possible.	5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total mortality		5 years
Total major vascular events	The composite of stroke, acute coronary syndrome or vascular death	5 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood Pressure		5 years
Urinary sodium excretion		5 years
Urinary Potassium		5 years
Knowledge about sodium and salt substitute	Knowledge about sodium and salt substitute will be measured using the following questions at baseline and follow-up:. Is a high salt intake good for your health? Does how much salt you eat affect your blood pressure? Does how much salt you eat affect your risk of stroke? What is the daily recommended salt intake for adults? Do you try to reduce the amount of salt you eat? Do you eat pickled vegetables most days? Do you add salt to most meals? Do you add mono-sodium glutamate to most meals? Do you try to eat less of a food if it is very salty? Have you heard about low sodium salt? If yes,does your household use low-sodium salt?	5 years

Collaborators and Investigators

• Sponsor: The George Institute
• Collaborators: Peking University; China Medical University, China; Northwestern University; Imperial College London; Health Science Center of Xi'an Jiaotong University; Ningxia Medical University; Changzhi Medical College; Centers for Disease Control and Prevention, China
• Investigators: Principal Investigator: Bruce C Neal, PhD, The George Institute for Global Health, Australia; Principal Investigator: Yangfeng Wu, PhD, The George Institute for Global Health at Peking University Health Science Centre; Principal Investigator: Darwin Labarthe, PhD, Northwestern University Feinberg School of Medicine; Principal Investigator: Paul Elliott, PhD, School of Public Health, Imperial College London; Principal Investigator: Lijing L Yan, PhD, The George Institute for Global Health at Peking University Health Science Centre; Principal Investigator: Nicole Y Li, PhD, The George Institute for Global Health, Australia

Publications and helpful links

General Publications

• Neal B, Wu Y, Feng X, Zhang R, Zhang Y, Shi J, Zhang J, Tian M, Huang L, Li Z, Yu Y, Zhao Y, Zhou B, Sun J, Liu Y, Yin X, Hao Z, Yu J, Li KC, Zhang X, Duan P, Wang F, Ma B, Shi W, Di Tanna GL, Stepien S, Shan S, Pearson SA, Li N, Yan LL, Labarthe D, Elliott P. Effect of Salt Substitution on Cardiovascular Events and Death. N Engl J Med. 2021 Sep 16;385(12):1067-1077. doi: 10.1056/NEJMoa2105675. Epub 2021 Aug 29.
• Li KC, Tian M, Neal B, Huang L, Yu J, Liu Y, Yin X, Zhang X, Wu Y, Li N, Elliott P, Yan L, Labarthe D, Hao Z, Shi J, Feng X, Zhang J, Zhang Y, Zhang R, Zhou B, Li Z, Sun J, Zhao Y, Yu Y, Si L, Lung T. Protocol for the economic evaluation of the China Salt Substitute and Stroke Study (SSaSS). BMJ Open. 2021 Jul 20;11(7):e045929. doi: 10.1136/bmjopen-2020-045929.

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2014
• Primary Completion (Actual): September 4, 2020
• Study Completion (Actual): September 4, 2020

Study Registration Dates

• First Submitted: March 12, 2014
• First Submitted That Met QC Criteria: March 17, 2014
• First Posted (Estimate): March 19, 2014

Study Record Updates

• Last Update Posted (Actual): April 8, 2021
• Last Update Submitted That Met QC Criteria: April 5, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Keywords: China; stroke; cluster randomized trial; salt substitute; sodium reduction
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: SSaSS; Grant ID 1049417 (Other Grant/Funding Number: Australian National Health and Medical Research Council)