TAIM 1992.

Methods	DESIGN: 3x3 factorial, randomised, open design DURATION: 6 months (phase I) NUMBER OF STUDY CENTRES: 3 COUNTRY OF PUBLICATION: USA SPONSOR: National Heart, Lung and Blood Institute
Participants	WHO PARTICIPATED: obese hypertensive patients The trial consisted of 2 phases. Phase I was performed in a 3*3 factorial design with follow‐up of 6 months. Phase II was performed in a 2*2 factorial design (usual care vs weight‐reducing diet). Since drop‐out in usual‐care group was 29% to 36% for phase II, only phase I will be analysed SETTING: outpatient clinic at 3 university hospitals (Bronx (New York), Birmingham (Alabama), Jackson (Mississippi)) MAIN INCLUSION CRITERIA: age 21 to 65 years; 110% to 116% of ideal body weight; sitting DBP (preliminary screened: treated ≤ 100 mm Hg, untreated 90 to 104 mm Hg; first clinic visit: 90 to 100 mm Hg; second clinic visit: < 115 mm Hg); no antihypertensive medication or discontinuation of current medication for at least 2 weeks before baseline BP measurement MAIN EXCLUSION CRITERIA: myocardial infarction within 1 year before study entry; medical history of stroke, bronchial asthma, insulin‐dependent diabetes mellitus, or allergy to thiazides or ß‐blockers; other major diseases (e.g. kidney disease, liver disease, or cancer); baseline creatinine ≥ 2 mg/dl; pregnancy; scheduled surgery NUMBER: 878 participants randomised Placebo groups (weight loss vs usual diet) NUMBER: 100 vs 100 randomised, 89 vs 90 analysed GENERAL BASELINE CHARACTERISTICS: MEAN AGE [YEARS]: 49 vs 47 GENDER [% MALE]: 59 vs 41 NATIONALITY: USA ETHNICITY: white: 67% vs 65%; black: 33% vs 35% WEIGHT [kg]: 90 vs 86 (199 lbs. vs 190 lbs.) BODY MASS INDEX [kg/m2]: ‐ (% ideal weight 138 vs 136) SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 142 vs 144 SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 93 vs 93 COMORBID CONDITIONS: smokers: 14% vs 15%, alcohol use (≥ 1 drink/week): 35% vs 37% ANTIHYPERTENSIVE TREATMENT: 63% vs 65% DURATION OF HYPERTENSION: ‐ SUBGROUP ANALYSES: ‐ Chlorthalidone groups (weight loss vs usual diet) NUMBER: 95 vs 97 randomised, 86 vs 87 analysed GENERAL BASELINE CHARACTERISTICS: MEAN AGE [YEARS]: 47 vs 49 GENDER [% MALE]: 50 vs 60 NATIONALITY: USA ETHNICITY: white: 67% vs 67%; black: 33% vs 33% WEIGHT [kg]: 87 vs 89 (192 lbs. vs 197 lbs.) BODY MASS INDEX [kg/m2]: ‐ (% ideal weight 138 vs 137) SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 138 vs 142 SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 92 vs 92 COMORBID CONDITIONS: smokers: 18% vs 13%, alcohol use (≥ 1 drink/week): 39% vs 42% ANTIHYPERTENSIVE TREATMENT: 61% vs 70% DURATION OF HYPERTENSION: ‐ SUBGROUP ANALYSES: ‐ Atenolol groups (weight loss vs usual diet) NUMBER: 96 vs 99 randomised, 88 vs 87 analysed GENERAL BASELINE CHARACTERISTICS: MEAN AGE [YEARS]: 48 vs 48 GENDER [% MALE]: 52 vs 64 NATIONALITY: USA ETHNICITY: white: 67% vs 67%; black: 33% vs 33% WEIGHT [kg]: 88 vs 89 (193 lbs. vs 195 lbs.) BODY MASS INDEX [kg/m2]: ‐ (% ideal weight 136 vs 136) SITTING SYSTOLIC BLOOD PRESSURE [mm Hg]: 144 vs 141 SITTING DIASTOLIC BLOOD PRESSURE [mm Hg]: 94 vs 93 COMORBID CONDITIONS: smokers: 14% vs 20%, alcohol use (≥ 1 drink/week): 37% vs 44% ANTIHYPERTENSIVE TREATMENT: 66% vs 63% DURATION OF HYPERTENSION: ‐ SUBGROUP ANALYSES: ‐
Interventions	LENGTH OF FOLLOW‐UP: 6 months (phase I) DIETARY INTERVENTION: weight‐reducing diet (standard program of diet counselling and nutrition education with the goal of a reduction of 10% of baseline weight or 4.54 kg, whichever was greater); 10 weekly group sessions within the first 6 months, subsequently individual or group counselling sessions with a nutritionist at least every 6 weeks, after 12 months dietary counselling on a quarterly basis NO DIETARY INTERVENTION: no diet and nutritional counselling or education ADDITIONAL TREATMENT: pharmacological antihypertensive treatment according to subgroup allocation (placebo or diuretic or ß‐blocker); medication was stepped up if BP reached predefined escape levels; regular monthly clinic visits for the first 6 months, every 3 months thereafter
Outcomes	PRIMARY OUTCOMES: 1. MORTALITY: ‐ 2. CARDIOVASCULAR MORBIDITY: ‐ 3. ADVERSE EVENTS: ‐ SECONDARY OUTCOMES: 1. CHANGES IN SYSTOLIC BLOOD PRESSURE [mm Hg]: Definition: SBP change from baseline to endpoint visit 2. CHANGES IN DIASTOLIC BLOOD PRESSURE [mm Hg]: Definition: DBP change from baseline to endpoint visit 3. BODY WEIGHT [kg]: Definition: body weight change from baseline to endpoint visit ADDITIONAL OUTCOMES MEASURED IN THE STUDY: 1. Change in sodium excretion 2. Change in potassium excretion 3. Quality of life (life satisfaction scale) 4. Symptoms and mental function (symptom checklist) 5. Expected side effects due to use of ß‐blocker (physical complaint inventory)
Notes
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	Comment: No details on sequence generation are provided
Allocation concealment (selection bias)	Unclear risk	Comment: Method of concealment is not described
Blinding (performance bias and detection bias) All outcomes	Low risk	Comment: The term double‐blind in all publications probably refers only to pharmacological treatment; there is no information on blinding concerning dietary interventions
Incomplete outcome data (attrition bias) All outcomes	High risk	WITHDRAWALS: 24 in all 9 groups within first month, 67 participants without BP measurement after 6 months REASONS/DESCRIPTIONS: ‐
Selective reporting (reporting bias)	Low risk	Comment: Outcomes are reported as prespecified
Other bias	High risk	Comment: 1. Step‐up medication: 20% (placebo/usual diet) vs 10% (placebo/weight‐reducing diets); it is unclear how many participants required an additional open‐label antihypertensive treatment; indication for step‐up therapy is presented inconsistently between study related publications 2. Unclear whether detection of endpoints was blinded 3. Number of randomised participants (878) is below calculated sample size (918), although 1940 participants were eligible