Bradley 1993.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 2 to 8 weeks (depending on previous use of anti‐hypertensive medication). Conducted in USA | |
| Participants | DBP 90 to 104 mmHg. Non‐smoking men. Mean age 51 years. Males 100%. Baseline BP was 140/92 mmHg in the treatment group and 145/91 mmHg in the control group | |
| Interventions | Chlorthalidone 45 mg/d (N = 16) or placebo (N = 18) Trial duration = 12 weeks | |
| Outcomes | Change from baseline in sitting SBP and DBP; LDL‐3, LDL‐1, LDL‐2, TG, VLDL, TC, HDL‐C, HDL‐2, HDL‐3, pulse rate, body weight; serum biochemistry (i.e. serum potassium, glucose and creatinine) and insulin. WDAEs | |
| Notes | A sample size calculation was based on change in LDL‐3; refer to Discussion p.639. BP was a secondary outcome measure of the study, and therefore statistical powering was based on LDL 3, the primary endpoint. No SD for BP data. Withdrawals due to adverse events were none. Patients were all non‐smoking, hypertensive males with mild hypertension. This inclusion criteria differ compared to studies with no restrictions on smoking and/or gender. A small sample size of 34 patients. There were no statistically significant differences (P value = NS) across treatment groups in patients' lipid levels, BP, glucose, insulin or body weight at baseline | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "...we conducted a randomized, double‐blind, placebo‐controlled, 12 week clinical trial..." (line 7 from bottom of p.636). "Participants were randomly assigned to treatment with 45 mg/day of chlorthalidone or placebo." (line 21 under "Design" p.637). Comment: no further information given on how patients were randomized |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "A double‐blind, placebo‐controlled, parallel group, 12 week trial was conducted." (line 1 under "Design" p.637). "Participants randomized to the chlorthalidone group took three 15 mg tablets once daily while those randomized to placebo took three identical placebo tablets." (line 28 under "Design" p.637) Comment: no further information given |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | Not known whether efficacy analysis was based on an ITT or per‐protocol technique Exclusions: no patients were excluded from study after the wash‐out period prior to randomization Attrition: t here was 1/18 (5.6%) withdrawals from the placebo group due to "symptomatic ulcerative colitis" WDAEs: it is presumed that the 1 patient withdrawal for "symptomatic ulcerative colitis" was considered to be an adverse event, however this is not stated explicitly by the study authors |
| Selective reporting (reporting bias) | High risk | Variability (i.e. SD) of mean change from baseline in BP was not given. Mortality, SAEs and AEs were not reported. Pulse, serum potassium, creatinine, insulin and glucose levels were measured at baseline and endpoint, however the change in mean ± SD at endpoint was not given. Variability for change in weight at endpoint was not given |
| Industry sponsorship | Unclear risk | Sponsor not reported |