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. 2022 Aug 10;2022(8):CD015207. doi: 10.1002/14651858.CD015207

Pan 2017.

Study characteristics
Methods Study design: Randomised controlled trial
Study grouping: Parallel group
Country: Taiwan
Setting: Intervention conducted in households; outcomes measured at 8 clinical centres
Aim of study: To evaluate the effects of potassium‐ and magnesium‐enriched salts on the neurologic performance of stroke patients
Unit of allocation: Adults (age 45 years and older)
Start date: December 2009
End date: May 2013
Relevant study limitations as reported by study authors: Lack of statistical power due to small sample size; synergistic effects of magnesium and potassium may be present; large dropout rate; under‐consumption of intervention salt and collection of first morning urine samples (instead of 24‐hour urine samples)
Sample size calculation: NR
Participants Baseline Characteristics
LSSS intervention (≥ 30% KCl)

  • Age: in years, mean (SD): 64.4 (9.8)

  • Gender: Female, % (n/N): 42.3 (41/97)

  • Ethnicity/race: Taiwanese

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: Hypertensive, %(n/N): 56.7 (55/97)

  • Antihypertensive medication used: NR

  • Cardiovascular disease or stroke: Ischaemic stroke, % (n/N): 94.8 (92/97); stroke, haemorrhagic stroke, % (n/N): 5.2 (5/97); hyperlipidaemia, % (n/N): 37.1 (36/97)

  • Diabetes mellitus: %, (n/N): 33.0 (32/97)

  • Renal impairment: GFR < 60 mL/min, % (n/N): 0 (0/97)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: NR

  • Urinary sodium excretion: NR


LSSS intervention (≥ 30% KCl)

  • Age: in years, mean (SD): 64.7 (9.9)

  • Gender: Female, % (n/N): 34.7 (33/95)

  • Ethnicity/race: Taiwanese

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: Hypertensive, %(n/N): 68.4 (62/95)

  • Antihypertensive medication used: NR

  • Cardiovascular disease or stroke: Ischaemic stroke, % (n/N): 93.7 (89/95); haemorrhagic stroke, % (n/N): 6.3 (6/95); hyperlipidaemia, % (n/N): 44.2 (42/95)

  • Diabetes mellitus: %, (n/N): 30.5 (29/95)

  • Renal impairment: GFR < 60mL/min, % (n/N): 0 (0/95)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: NR

  • Urinary sodium excretion: NR


Control

  • Age: in years, mean (SD): 64.8 (10.3)

  • Gender: Female, % (n/N): 32.3 (32/99)

  • Ethnicity/race: Taiwanese

  • Smoking: NR

  • Body Mass Index (BMI): NR

  • Blood pressure status: Hypertensive, %(n/N): 50.5 (50/99)

  • Antihypertensive medication used: NR

  • Cardiovascular disease or stroke: Ischaemic stroke, % (n/N): 91.9 (91/99); haemorrhagic stroke, % (n/N): 8.1 (8/99); hyperlipidaemia, % (n/N): 39.4 (39/99)

  • Diabetes mellitus: %, (n/N): 40.4 (40/99)

  • Renal impairment: GFR < 60mL/min, % (n/N): 0 (0/99)

  • Dietary potassium intake: NR

  • Dietary sodium intake: NR

  • Urinary potassium excretion: NR

  • Urinary sodium excretion: NR


Inclusion criteria: Adults, aged 45 years and older, who were hospitalised for <= 1 month because of cerebral infarction or haemorrhage, with a modified Rankin scale (mRS) score of <= 4 at the time of discharge, who agreed to prepare foods with salt provided by the study
Exclusion criteria: Patients with poor kidney function (GFR < 60 mL/min), secondary hypertension, cancer, or liver diseases, those with eating disorders; those taking potassium‐sparing medicines, or consuming salt substitutes
Pretreatment: None reported at baseline. However, the proportion of participants with hypertension in the control group (50.5%) was lower compared to the intervention groups, especially the < 50% KCl group (68.4%).
Method of recruitment of participants: Medical practitioners at 8 participating hospitals identified potentially eligible patients.
Informed consent obtained: yes (written)
Clusters: n/a
Subgroups planned/measured: NR
Subgroups reported: NR
Participant flow
Assessed for eligibility: NR
Excluded (number with reasons): NR
Randomised: n = 291
Allocated to LSSS intervention/s: n = 97 (LSSS 50% KCl); n = 95 (LSSS < 50% KCl)
Allocated to control: n = 99
Received allocated LSSS intervention/s: NR
Did not receive allocated LSSS intervention/s: NR
Lost to follow‐up (LSSS intervention group): 
At 3 months: n = 21 (LSSS 50% KCl) ‐ Reasons: Moved away (n = 2), hospital transfer (n = 1), left study (n = 15), lost to follow‐up (n = 3)n = 20; (LSSS < 50% KCl)‐ Reasons: Suicidal death (n = 1), hospital transfer (n = 2), left study (n = 16), lost to follow‐up (n = 1)
At 6 months: n = 14 (LSSS 50% KCl)‐ Reasons: Hospital transfer (n = 3), left study (n = 9), lost to follow‐up (n = 2) n = 11; (LSSS < 50% KCl) ‐ Reasons: Hospital transfer (n = 1), left study (n = 8), lost to follow‐up (n = 2)
Discontinued intervention (LSSS intervention group): At 3 months: n = 15 (LSSS 50% KCl) n = 16 (LSSS < 50% KCl)
At 6 months: n = 9 (LSSS 50% KCl) n = 8 (LSSS < 50% KCl)
Analysed (LSSS intervention group): n = 97 (LSSS 50% KCl); n = 95 (LSSS < 50% KCl) ‐ ITT analysis was performed (the last‐observation‐carried‐forward method)
Excluded from analysis (LSSS intervention group): NR
Received allocated control: NR
Did not receive allocated control: NR
Lost to follow‐up (control group): 
At 3 months: n = 15 Reasons ‐ Suicidal death (n = 1), hospital transfer (n = 1), left study (n = 12), lost to follow‐up (n = 1)
At 6 months: n = 13 Reasons ‐ Hospital transfer (n = 1), left study (n = 10), lost to follow‐up (n = 2)
Discontinued intervention (control group): 
At 3 months: n = 12
At 6 months: n = 10
Analysed (control group): n = 99 ‐ ITT analysis was performed (the last‐observation‐carried‐forward method)
Excluded from analysis (control group): NR
 
Interventions Intervention Characteristics
LSSS intervention (50% KCl)

  • Theoretical basis: Provision of an adequate intake of potassium to stroke patients, for the maintenance of neurologic and cardiovascular health 

  • Description: K salt (NaCl 50%; KCl 50%). Approx. consumption of 6.5g 'K' salt per person/day (1278 mg or 55.6 mmol Na; 1701 mg or 43.6 mmol K)

  • LSSS category: ≥ 30% KCl

  • Contains fortificant: NR

  • Delivery: discretionary use

  • Duration of run‐in period: none

  • Duration of active intervention: 6 months

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

  • Total duration of study (as reported): 6 months

  • Timing: daily household use

  • Implementation: 1 kg salt was provided at study entry and replenished at the 3‐month outpatient visit.

  • Providers: Medical practitioners were responsible for salt distribution; manufacturer NR

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Salt consumption, in grams per 3 months, mean (SD): 361.5 (301.5); n = 71; 328.5 (220.2); n = 60


LSSS intervention (< 50% KCl)

  • Theoretical basis: Provision of an adequate intake of potassium and magnesium to stroke patients, for the maintenance of neurologic and cardiovascular health 

  • Description: 'K/Mg' salt (42.85% NaCl, 42.85% KCl, 14.3% MgSO4). Approx. consumption of 6.5g 'K/Mg' salt per person/day (2785 mg or 47.6 mmol Na; 2785 mg or 44.9 mmol K and 929.5 mg (3.8 mmol))

  • LSSS category: ≥ 30% KCl

  • Contains fortificant: NR

  • Delivery: discretionary use

  • Duration of run‐in period: none

  • Duration of active intervention: 6 months

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

  • Total duration of study (as reported): 6 months

  • Timing: daily household use

  • Implementation: 1 kg salt was provided at study entry and replenished at the 3‐month outpatient visit.

  • Providers: Medical practitioners were responsible for salt distribution; manufacturer NR

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Salt consumption, in grams per 3 months, mean (SD): 328.2 (238.3); n = 72; 350.7 (346.0); n = 59


Control

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

  • Description: Regular salt. Approx. consumption of 6.5 g salt per person/day (2555 mg Na or 111 mmol Na)

  • Contains fortificant: NR

  • Delivery: discretionary use

  • Duration of run‐in period: none

  • Duration of active intervention: 6 months

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

  • Total duration of study (as reported): 6 months

  • Timing: daily household use

  • Implementation: 1 kg salt was provided at study entry and replenished at the 3‐month outpatient visit.

  • Providers: Medical practitioners were responsible for salt distribution; manufacturer NR

  • Co‐interventions: NR

  • Resource requirements: NR

  • Integrity of delivery: Salt consumption, in grams per 3 months, mean (SD): 425.2 (344.4); n = 81; 332.4 (223.3); n = 68
Outcomes Primary outcomes: 

  • Diastolic Blood Pressure (DBP): NR

  • Systolic Blood Pressure (SBP): NR

  • 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: Outcome measurement: NR; time points: 3, 6 months

  • Cardiovascular events‐myocardial infarction: NR

  • Cardiovascular events‐other: NR

  • Cardiovascular mortality: NR

  • Blood potassium: NR

  • Hyperkalaemia: NR

  • Hypokalaemia: NR


Secondary outcomes

  • All‐cause mortality: Outcome measurement: NR; time points: 3, 6 months

  • Adverse events: Outcome measurement (serious AEs): NR; time points: duration of the study

  • 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: NR

  • 24‐h urinary potassium excretion: NR
Notes Funding source: Supported by grants from the Institute of Biomedical Sciences, Academia Sinica, and from the Ministry of Health and Welfare (DOH098‐TD‐F‐113‐098030).
Authors name: Wen‐Harn Pan
Institution: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan
Email: pan@ibms.sinica.edu.tw
Possible conflicts of interest (for study authors): None.
Sources used for data extraction: Journal article with results of the trial
Trial registration details: NCT02910427
Risk of bias
Bias Authors' judgement Support for judgement
Random sequence generation (selection bias) Low risk Computerised block randomisation sequence generation. A stratified randomisation method was used according to a clinical history of ischaemic or haemorrhagic stroke, diabetes or no diabetes, and the use of magnesium‐containing medication or not.
Allocation concealment (selection bias) Low risk Salts were labelled by numbers 1, 2, 3 during manufacturing. Allocation was performed by software once the participant's details were entered.
Blinding of participants and personnel (performance bias)
All outcomes Low risk The study authors reported that participants and personnel, such as the medical practitioners involved in the salt distribution, were blinded.
Blinding of outcome assessment (detection bias)
All outcomes Low risk The medical practitioners performing the patient evaluations were blinded.
Incomplete outcome data (attrition bias)
All outcomes Low risk Incomplete data reported at 6 months were 34% (33/97)(LSSS 50% KCl) and 34.7% (33/95) (LSSS < 50% KCl), compared to 28.3% (28/99) in the control group. The study authors stated that no significant difference was found in baseline characteristics between participants who remained in the study at month 3 and at month 6, compared to those who did not. The study authors conducted an ITT analysis (last‐observation‐carried‐forward).
Selective reporting (reporting bias) Low risk Primary outcomes reported according to those pre‐specified in the study protocol (NCT02910427)
Other bias Low risk None identified
Overall risk of bias Low risk Low risk of bias for allocation concealment and incomplete outcome data