TONE 1998.
| Methods | DESIGN: parallel, 2x2 factorial, randomised, blinded endpoint evaluation design DURATION: 15 to 36 months NUMBER OF STUDY CENTRES: 4 COUNTRY OF PUBLICATION: USA SPONSOR: National Heart , Lung and Blood Institute and National Institute on Aging grants | |
| Participants | WHO PARTICIPATED: elderly, obese, and hypertensive patients; participants were assigned to active intervention: sodium reduction (S+), or weight loss, or sodium reduction (S+) and weight loss vs usual care
SETTING: outpatient clinic MAIN INCLUSION CRITERIA: age 60 to 80 years; BMI ≥ 27.8 kg/m2 (male), BMI ≥ 27.3 kg/m2 (women); SBP < 145 mm Hg and DBP < 85 mm Hg while taking 1 antihypertensive medication or 2 antihypertensive medications if 1 can be stopped during screening phase (combination of 1 diuretic and 1 non‐diuretic drug are considered as 1 drug) MAIN EXCLUSION CRITERIA: heart attack or stroke within preceding 6 months; angina; congestive heart failure; insulin‐dependent diabetes mellitus; BMI > 33 kg/m2 (men), BMI > 37 kg/m2 (women); unexplained or involuntary weight loss of 4.5 kg or greater during previous year; hypercreatinaemia; hyperkalaemia; hyperglycaemia; anaemia Dietary‐intervention (IG‐S‐) vs no dietary‐intervention group (CG‐S‐) NUMBER: 147 vs 147 participants were randomised; no information on numbers of participants analysed, however 96% to 99% were included for analysis at study end GENERAL BASELINE CHARACTERISTICS: MEAN AGE [YEARS]: 66 vs 66 GENDER [% MALE]: 49% vs 41% NATIONALITY: USA ETHNICITY: white: 73% vs 68%; African American: 26% vs 32% WEIGHT [kg]: 87 vs 86 BODY MASS INDEX [kg/m2]: 31 vs 31 SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 130 vs 128 SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 72 vs 72 COMORBID CONDITIONS: ‐ ANTIHYPERTENSIVE TREATMENT: 100% vs 100% DURATION OF HYPERTENSION [YEARS]: 11 vs 12 Dietary intervention and salt restriction (IG‐S+) vs no dietary intervention and salt restriction group (CG‐S+) NUMBER: 147 vs 144 participants were randomised; no information on numbers of participants analysed, however 96% to 99% were included for analysis at study end GENERAL BASELINE CHARACTERISTICS: MEAN AGE [YEARS]: 66 vs 66 GENDER [% MALE]: 56% vs 44% NATIONALITY: USA ETHNICITY: white: 76% vs 70%; African American: 24% vs 30% WEIGHT [kg]: 86 vs 88 BODY MASS INDEX [kg/m2]: 31 vs 31 SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 129 vs 129 SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 72 vs 72 COMORBID CONDITIONS: ‐ ANTIHYPERTENSIVE TREATMENT: 100% vs 100% DURATION OF HYPERTENSION [YEARS]: 12 vs 12 SUBGROUP ANALYSES: age, gender, ethnicity |
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| Interventions | LENGTH OF FOLLOW‐UP: 15 to 36 months DIETARY INTERVENTION: achieving and maintaining a weight loss of 4.5 kg or greater; structured programmes with dietary advice provided to participants mainly in small groups to change their eating behaviours and to motivate participants to achieve and maintain their desired reductions; participants were required to increase amount of physical activity, but no detailed information was provided NO DIETARY INTERVENTION: no study‐related counselling ADDITIONAL TREATMENT: Salt restriction (S+): achieving and maintaining a 24‐hour dietary sodium intake of 80 mmol or less (as measured by 24‐hour urine collection) |
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| Outcomes |
PRIMARY OUTCOMES:
1. MORTALITY: reported
2. CARDIOVASCULAR MORBIDITY: reported
3. ADVERSE EVENTS:
Definition: presumed adverse events were assessed using a standardised approach that included questioning of participants, family members, and physicians and a review of physicians' records with blinded evaluation SECONDARY OUTCOMES: 1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]: ‐ 2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]: ‐ 3. BODY WEIGHT [kg]: reported for the combined groups only (both intervention (IG‐S+ and IG‐S‐) vs both control (CG‐S+ and CG‐S‐) groups) ADDITIONAL OUTCOMES MEASURED IN THE STUDY: 1. Primary study endpoint: failure of antihypertensive drug withdrawal due to: a. occurrence of high blood pressure measured at 1 or more follow‐up visits according predefined values; b. restart of treatment with antihypertensive medication due to other reasons or based on the decision of the treating doctors or study participants; c. occurrence of clinical cardiovascular disease complications during follow‐up. 2. Weight reduction |
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| Notes | ||
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | Quote: "using a computer program ... stratified by clinic and weight status ... blocking of variable length" |
| Allocation concealment (selection bias) | Unclear risk | Comment: Method of concealment is not described |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | Comment: Participants, study personnel were not blinded, but an independent committee masked to intervention assignment evaluated the endpoints |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Comment: Numbers of withdrawals and reasons are missing, however 96% to 99% of participants were included at follow‐up analysis WITHDRAWALS: ‐ REASONS/DESCRIPTIONS: ‐ |
| Selective reporting (reporting bias) | Low risk | Comment: Outcomes are reported as prespecified |
| Other bias | Low risk | ‐ |
BMI: body mass index BP: blood pressure DBP: diastolic blood pressure HDFP: Hypertension Detection an Follow‐up Program HDL: high‐density lipoprotein LOCF: last observation carried forward analysis SBP: systolic blood pressure