Skip to main content
. 2022 Aug 10;2022(8):CD015207. doi: 10.1002/14651858.CD015207

Yu 2021.

Study characteristics
Methods Study design: Randomised controlled trial
Study grouping: Parallel group
Country: India
Setting: Intervention conducted in villages in northern region of the Indian state of Telangana; outcomes measured during face‐to‐face follow‐up visits of households
Comments: Salt Substitute in India Study (SSiIS)
Aim of study: The primary aim of SSiIS is to evaluate the effect of a 3‐month reduced‐sodium, added‐potassium salt substitute intervention on SBP among patients with hypertension in rural India. The secondary aims are to determine the effects of the salt substitute on DBP, urinary sodium and potassium excretion, as well as to assess dietary sources of sodium and the acceptability of the salt substitute.
Unit of allocation: Adults (age 18 years and older)
Start date: November 2019
End date: April 2020
Relevant study limitations as reported by study authors: Short intervention duration; findings may not be generalisable to urban Indian hypertensive populations; exclusion of hypertensive patients with kidney disease; cannot rule out presence of undetected hyperkalaemia in some participants; no collection of 24‐hour urine biomarkers at one month follow‐up to determine trajectory of changes in urinary sodium and potassium over the study period, and did not assess the completeness of 24‐hour urine collections by administration of para‐aminobenzoic acid
Sample size calculation: Estimated sample size was 498 participants, at 80% power and a significance level of 5% (one‐sided test). The power estimate assumed a mean baseline SBP of 140 mmHg (SD 20 mmHg) and a 20% loss to follow‐up. The study was powered to detect a 5 mmHg or greater difference in mean SBP between groups.
Participants Baseline Characteristics
LSSS intervention

  • Age: in years, mean (SD): 61.5 (11.1)

  • Gender: Female, % (n/N): 58.3 (147/252)

  • Ethnicity/race: Asian

  • Smoking: Current smoking, % (n/N): 6.3 (16/252); past smoking, % (n/N): 8.3 (21/252)

  • Body Mass Index (BMI): in kg per m2, mean (SD): 23.1 (4.7)

  • Blood pressure status: Hypertensive, % (n/N): 100 (252/252)

  • Antihypertensive medication used: Any hypertensive medication use, % (n/N): 97.2 (245/252); diuretic, % (n/N): 0 (0/252); calcium channel blockers, % (n/N): 2.4 (6/252); ACE inhibitor or ARB, % (n/N): 27.8 (70/252); beta‐blockers, % (n/N): 25.0 (63/252); alpha‐blocker, % (n/N): 42.5 (107/252)

  • Cardiovascular disease or stroke: History of CVD, % (n/N): 1.2 (3/252)

  • Diabetes mellitus: History of DM, % (n/N): 23.4 (59/252)

  • Renal impairment: Acute or chronic kidney disease, % (n/N): 0 (0/252)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: in grams (24 hours), mean (SD): 0.82 (0.45)

  • Urinary sodium excretion: in grams (24 hours), mean (SD): 3.80 (1.86)


Control

  • Age: in years, mean (SD): 61.7 (12.9)

  • Gender: Female, % (n/N): 59.2 (148/250)

  • Ethnicity/race: Asian

  • Smoking: Current smoking, % (n/N): 5.6 (14/250); past smoking, % (n/N): 8.0 (20/250)

  • Body Mass Index (BMI): in kg per m2, mean (SD): 23.6 (4.2)

  • Blood pressure status: Hypertensive, % (n/N): 100 (250/250)

  • Antihypertensive medication used: Any hypertensive medication use, % (n/N): 94..4 (236/250); diuretic, % (n/N): 0.4 (1/250); calcium channel blockers, % (n/N): 3.6 (9/250); ACE inhibitor or ARB, % (n/N): 32.0 (80/250); beta‐blockers, % (n/N): 20.0 (50/250); alpha‐blocker, % (n/N): 39.0 (97/250)

  • Cardiovascular disease or stroke: History of CVD, % (n/N): 1.6 (4/250)

  • Diabetes mellitus: History of DM, % (n/N): 20.5 (51/250)

  • Renal impairment: Acute or chronic kidney disease, % (n/N): 0 (0/250)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: in grams (24 hours), mean (SD): 0.86 (0.53)

  • Urinary sodium excretion: in grams (24 hours), mean (SD): 3.64 (1.73)


 
Overall

  • Age: NR

  • Gender: NR

  • Ethnicity/race: Asian

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: NR

  • Antihypertensive medication used: NR

  • Cardiovascular disease or stroke: NR

  • Diabetes mellitus: NR

  • Renal impairment: Acute or chronic kidney disease, % (n/N): 0 (0/502)

  • Renal impairment: NR

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: NR

  • Urinary sodium excretion: NR


Inclusion criteria: Adults aged 18 years or over with a history of hypertension diagnosed by a health professional (hypertension may be self‐reported and antihypertensive drugs may or may not be used for management) who eat most of their meals at home.
Exclusion criteria: Participants or any of their household members with self‐reported acute or chronic kidney disease (according to standard diagnostic clinical criteria; verified by study physician at baseline), who used potassium‐sparing diuretics, potassium supplements, who were not expected to live longer than 6 months from the baseline assessment, or where another household member was already enrolled in the study
Pretreatment: Baseline clinical and demographic characteristics of participants were similar between the intervention and the control group.
Method of recruitment of participants: Villages were purposively selected based on their willingness to be involved and their proximity to the infrastructure necessary for the study, including delivery of the intervention salts and being accessible to study personnel. After we approached the households, each household decided for themselves which of the adult members of the household (who also met eligibility criteria) would be the study participant.
Informed consent obtained: Yes (written consent)
Clusters: n/a
Subgroups planned/measured: NR
Subgroups reported: Age < 65 years vs. >= 65 years; male vs. female; diabetes vs. no diabetes
 
Participant flow
Assessed for eligibility: n = 1923
Excluded (number with reasons): n = 1421 (n = 286 eat most meals outside the home; n = 21 withdrew consent; n = 350 had concerns about use of LSSS; n = 206 used a potassium‐sparing diuretic; n = 193 used potassium supplements; n = 117 had kidney disease; n = 132 another household member already enrolled; n = 101 not interested)
Randomised: n = 502
Allocated to LSSS intervention(s): n = 252
Allocated to control: n = 252
Received allocated LSSS intervention(s): NR
Did not receive allocated LSSS intervention(s): NR
Lost to follow‐up (LSSS intervention group): n = 3 at 1 month (n = 2 lost contact; n = 1 death); n = 6 at 3 months (n = 4 lost contact; n = 2 hospitalised)
Discontinued intervention (LSSS intervention group): n = 1 at 3 months
Analysed (LSSS intervention group): SBP; DBP: n = 242; urinary sodium and potassium (24‐hour urine): n = 238; questionnaire: n = 242
Excluded from analysis (LSSS intervention group): Urinary sodium and potassium: n = 26 excluded due to incomplete urine samples
Received allocated control: NR
Did not receive allocated control: NR
Lost to follow‐up (control group): n = 3 at 1 month (n = 3 lost contact); n = 7 at 3 months (n = 7 lost contact)
Discontinued intervention (control group): n = 3 at 1 month; n = 3 at 3 months
Analysed (control group): SBP, DBP: n = 234; urinary sodium and potassium (24‐hour urine): 224; questionnaire: 234
Excluded from analysis (control group): Urinary sodium and potassium: n = 29 excluded due to incomplete urine samples
Interventions Intervention Characteristics
LSSS intervention

  • Theoretical basis: LSSS may lower SBP and DBP through reduced dietary sodium and increased potassium consumption.

  • Description: Reduced‐sodium, added‐potassium salt substitute (70% sodium chloride; 30% potassium chloride)

  • LSSS category: ≥ 30% KCl

  • Contains fortificant: iodine

  • Delivery: discretionary use

  • Duration of run‐in period: none

  • Duration of active intervention: 3 months

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 3 months

  • Timing: LSSS provided to replace all household salt, and be used in cooking, seasoning and food preservation throughout the study

  • Implementation: Provision of a 3‐month supply by study personnel during second face‐to‐face study visit to household (calculated as an average of 20 g/person/day to a maximum of 5 kg per 3 months for a household)

  • Providers: Siddharth Starch Pvt. Ltd. company based in Maharashtra, India blended and supplied the LSSS.

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Acceptability and adherence assessed with questionnaire. Reported LSSS use at 1 month: No. of days in week prior, mean (SD): 6.5 (1.6). No. of meals per typical day, mean (SD): 2.7 (0.8). Reported LSSS use at 3 months: No. of days in week prior, mean (SD): 6.3 (1.8). No. of meals per typical day, mean (SD): 2.6 (0.6)


Control

  • Theoretical basis: To enable comparison of LSSS intervention with standard practice

  • Description: Regular salt (100% sodium chloride)

  • Contains fortificant: iodine

  • Delivery: discretionary use

  • Duration of run‐in period: none

  • Duration of active intervention: 3 months

  • Duration of follow‐up (as reported): none

  • Total duration of study (as reported): 3 months

  • Timing: Regular salt provided to replace all household salt, and be used in cooking, seasoning and food preservation throughout the study

  • Implementation: Provision of a 3‐month supply by study personnel during second face‐to‐face study visit to household (calculated as an average of 20 g/person/day to a maximum of 5 kg per 3 months for a household)

  • Providers: Siddharth Starch Pvt. Ltd. company based in Maharashtra, India supplied regular salt.

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Acceptability and adherence assessed with questionnaire. Reported LSSS use at 1 month: No. of days in week prior, mean (SD): 6.4 (1.6). No. of meals per typical day, mean (SD): 2.6 (0.5). Reported LSSS use at 3 months: No. of days in week prior, mean (SD): 6.3 (1.8). No. of meals per typical day, mean (SD): 2.5 (0.7)
Outcomes Primary outcomes: 

  • Diastolic Blood Pressure (DBP): Outcome measurement: measured three times for each participant, in a sitting position in a quiet room, using an automated BP monitor (A&D Medical) according to standardised methods and criteria, and the mean of the last two measurements was recorded. Time points: 1, 3 months

  • Systolic Blood Pressure (SBP): Outcome measurement: measured three times for each participant, in a sitting position in a quiet room, using an automated BP monitor (A&D Medical) according to standardised methods and criteria, and the mean of the last two measurements was recorded. Time points: 1, 3 months

  • Hypertension (as reported, or SBP > 140 mmHg or DBP > 85 mmHg): NR

  • Blood pressure control (achieving blood pressure threshold or 'control' as prespecified): NR

  • Cardiovascular events‐stroke: NR

  • Cardiovascular events‐myocardial infarction: NR

  • Cardiovascular events‐other: NR

  • Cardiovascular mortality: NR

  • Blood potassium: NR

  • Hyperkalaemia: Outcome measurement: Investigation of suspected clinical cases of hyperkalaemia (methods NR); time points: 1, 3 months

  • Hypokalaemia: NR


 
Secondary outcomes: 

  • All‐cause mortality: NR

  • Adverse events: Outcome measurement: Recording of all adverse events among study participants or household members, whether likely to be related to the study intervention or not; time points: 1, 3 months

  • Antihypertensive medication use: NR

  • Body Mass index (BMI): NR

  • Serum creatinine: NR

  • Albuminuria: NR

  • Urinary albumin‐to‐creatinine ratio (uACR): NR

  • Fasting blood glucose: NR

  • Blood triglycerides: NR

  • Total blood cholesterol: NR

  • 24‐h urinary sodium excretion: 24‐hour urine sample. Time points: 3 months

  • 24‐h urinary potassium excretion: 24‐hour urine sample. Time points: 3 months
Notes Funding source: The George Institute for Global Health Seed Grant (grant number 0141030). Regular salt used in the study was provided free of charge by Siddharth Starch Pvt. Ltd. company.
Authors name: Jie Yu
Institution: The George Institute for Global Health, University of New South Wales, Sydney, New South Wales, Australia and Department of Cardiology, Peking University Third Hospital, Beijing, China
Email: jyu1@georgeinstitute.org.au
Possible conflicts of interest (for study authors): The authors reported no conflicts of interest.
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk The authors stated that random assignment occurred through a central computerised process, done by an independent biostatistician.
Allocation concealment (selection bias) Low risk Participants were allocated to either group according to a prepared random allocation sequence list, drawn up by an independent biostatistician.
Blinding of participants and personnel (performance bias)
All outcomes Low risk Participants and study personnel were blinded. LSSS and regular salt were provided as masked, identical packages, with only the unique identification number on each pack.
Blinding of outcome assessment (detection bias)
All outcomes Low risk Study personnel who collected outcome data were blinded.
Incomplete outcome data (attrition bias)
All outcomes Low risk BP data were available for 96 % (242/252) and 92.6% (234/250) of intervention and control participants, respectively. In addition, the study authors demonstrated that there were no differences in demographic and clinical characteristics of participants who completed the study, compared to those who did not (supplementary data).
Selective reporting (reporting bias) Unclear risk Primary and secondary outcomes reported according to the published study protocol. Pulse rate and medication use were indicated as outcomes at one and three months, but were not reported. Dietary recall (24 h) was also indicated as an outcome at three months, but was not reported. The authors reported a subgroup analysis which was not prespecified.
Other bias Low risk None identified
Overall risk of bias Low risk Low risk of bias for allocation concealment and incomplete outcome data