China Salt Substitute and Stroke Study

NCT ID: NCT02092090

Last Updated: 2021-04-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 20996 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-07-09
• Study Completion Date: 2020-09-04

Brief Summary

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.

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.

Conditions

Stroke

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Control

Dietary advice at baseline only

Group Type: NO_INTERVENTION

No interventions assigned to this group

Dietary sodium reduction

Dietary advice and reduced-sodium added-potassium salt substitute

Group Type: EXPERIMENTAL

Dietary sodium reduction

Intervention Type: BEHAVIORAL

Ongoing dietary advice and a supply of a reduced-sodium added-potassium salt substitute

Interventions

Dietary sodium reduction

Ongoing dietary advice and a supply of a reduced-sodium added-potassium salt substitute

Intervention Type: BEHAVIORAL

Other Intervention Names

Reduced-sodium added-potassium salt substitute

Eligibility Criteria

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

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University

OTHER

Sponsor Role: collaborator

Northwestern University

OTHER

Sponsor Role: collaborator

Imperial College London

OTHER

Sponsor Role: collaborator

China Medical University, China

OTHER

Sponsor Role: collaborator

Changzhi Medical College

OTHER

Sponsor Role: collaborator

Centers for Disease Control and Prevention, China

OTHER_GOV

Sponsor Role: collaborator

Ningxia Medical University

OTHER

Sponsor Role: collaborator

Xi'an Jiaotong University

OTHER

Sponsor Role: collaborator

The George Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Bruce C Neal, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Institute for Global Health, Australia

Yangfeng Wu, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Institute for Global Health at Peking University Health Science Centre

Darwin Labarthe, PhD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University Feinberg School of Medicine

Paul Elliott, PhD

Role: PRINCIPAL_INVESTIGATOR

School of Public Health, Imperial College London

Lijing L Yan, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Institute for Global Health at Peking University Health Science Centre

Nicole Y Li, PhD

Role: PRINCIPAL_INVESTIGATOR

The George Institute for Global Health, Australia

Locations

Hebei Province Centre for Disease Control and Prevention

Shijiazhuang, Hebei, China

China Medical Universtity

Shenyang, Liaoning, China

Ningxia Medical University

Yinchuan, Ningxia, China

Xi'an Jiaotong University

Xi'an, Shaanxi, China

Changzhi Medical Colledge

Changzhi, Shanxi, China

Countries

China

References

Zhang X, Yin X, Yap ML, Li Q, Huang L, Liu Y, Zhou B, Li Z, Zhao Y, Sun J, Yu Y, Yan LL, Wu Y, Neal B, Tian M. Effect of sodium-reduced potassium-enriched salt substitutes on stomach cancer: the Salt Substitute and Stroke Study (SSaSS). BMC Med. 2025 Apr 23;23(1):236. doi: 10.1186/s12916-025-04068-0.

Reference Type: DERIVED

PMID: 40264179 (View on PubMed)

Ding X, Zhang X, Huang L, Xiong S, Li Z, Zhao Y, Zhou B, Yin X, Xu B, Wu Y, Neal B, Tian M, Yan LL. Salt Substitution and Recurrent Stroke and Death: A Randomized Clinical Trial. JAMA Cardiol. 2025 Apr 1;10(4):343-350. doi: 10.1001/jamacardio.2024.5417.

Reference Type: DERIVED

PMID: 39908026 (View on PubMed)

Wang F, Pi Y, Zhao Y, Zhang Y, Zhou B, Li Z, Sun J, Yu Y, Tian M, Yang M, Huang L, Song H, Neal B, Kissock KR. Effect of salt substitution on fracture-a secondary analysis of the Salt Substitute and Stroke Study (SSaSS). BMC Med. 2024 Sep 4;22(1):366. doi: 10.1186/s12916-024-03586-7.

Reference Type: DERIVED

PMID: 39232779 (View on PubMed)

Yu J, Arnott C, Li Q, Di Tanna GL, Tian M, Huang L, Yin X, Zhang X, Pearson SA, Labarthe DR, Elliott P, Yan LL, Zhou B, Wu Y, Neal B. Secondary Analysis of the Salt Substitute and Stroke Study (SSaSS): Effects of Potassium-Enriched Salt on Cardiac Outcomes. Hypertension. 2024 May;81(5):1031-1040. doi: 10.1161/HYPERTENSIONAHA.123.22410. Epub 2024 Mar 11.

Reference Type: DERIVED

PMID: 38465623 (View on PubMed)

Haghdoost F, Gnanenthiran SR, Shan S, Kaistha P, Huang L, Tian M, Liu Y, Yin X, Zhang X, Hao Z, Wu Y, Di Tanna GL, Neal B, Rodgers A. The effect of salt substitution on frequency and severity of headache: results from the SSaSS cluster-randomised controlled trial of 20,995 participants. Eur J Clin Nutr. 2024 May;78(5):401-406. doi: 10.1038/s41430-024-01419-7. Epub 2024 Feb 24.

Reference Type: DERIVED

PMID: 38402353 (View on PubMed)

Yin X, Paige E, Tian M, Li Q, Huang L, Yu J, Rodgers A, Elliott P, Wu Y, Neal B. The Proportion of Dietary Salt Replaced With Potassium-Enriched Salt in the SSaSS: Implications for Scale-Up. Hypertension. 2023 May;80(5):956-965. doi: 10.1161/HYPERTENSIONAHA.122.20115. Epub 2023 Jan 11.

Reference Type: DERIVED

PMID: 36628969 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34459569 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34285006 (View on PubMed)

Other Identifiers

Grant ID 1049417

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SSaSS

Identifier Type: -

Identifier Source: org_study_id