Carlsen 1990.
| Methods | Randomized, double‐blind, placebo‐controlled dose‐ranging trial (parallel arms). Wash‐out period = 6 weeks. Conducted in New Zealand and Denmark | |
| Participants | DBP 100 to 120 mmHg. Mean age 57.4 years. Males 40%. Baseline BP was 165.2/104 mmHg in the treatment group and 161.9/101.8 in the control group | |
| Interventions | Bendrofluazide 1.25 mg (N = 50), 2.5 mg (N = 52), 5 (N = 52) or 10 mg/d (N = 51), or placebo (N = 52) Treatment duration = 12 weeks | |
| Outcomes | Sitting SBP and DBP (taken at 4, 10 and 12 weeks); BP response rate; heart rate; serum biochemistry | |
| Notes | A sample size calculation was provided based on 50 patients per treatment group to detect a difference in BP of 5 mmHg (SD ± 7 mmHg) between treatments (power level not given). Patients who took less than 80% of their tablets (placebo) during the 6‐week placebo run‐in period were excluded from entering the study. After taking placebo for 6 weeks only patients with DBP between 100 and 120 mmHg were included in the study. The 10 mg bendrofluazide dose was chosen based only on 1 prior trial by the Medical Research Council. The study's authors stated that "there were no large differences" between treatment groups in patients' baseline demographics and characteristics (Table 1 p.976) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "[Patients] were randomly allocated in blocks of 10 on a double‐blind basis to receive placebo or bendrofluazide at a dose of 1.25, 2.5, 5, or 10 mg a day." (line 1 under "Study Design" p.975). No further detail provided |
| Allocation concealment (selection bias) | Unclear risk | Not stated explicitly by study authors |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "[Patients] were randomly allocated in blocks of 10 on a double‐blind basis..." (line 1 under "Study Design" p.975). "Placebo and active tablets were identical in appearance and taste. All patients received four tablets daily, two in the morning and two at lunch. Those receiving fewer than four active tablets daily were given the active tablets in the morning." (line 15 from bottom under "Study Design" p.975) |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Not known whether efficacy analysis was based on an ITT or per‐protocol technique
Exclusions: number of patients excluded from study after the placebo run‐in period and before randomization was not reported Attrition: total withdrawals and reasons for withdrawing were not given WDAEs: 9/257 (3.5%) of patients withdrew due to adverse events (2 in placebo, 1.25, 2.5 and 10 mg group, and 1 in 5 mg group), however the precise reasons were not given |
| Selective reporting (reporting bias) | High risk | Sodium levels and pulse were measured both at beginning and end of study but not reported on. Variability in baseline patient demographics and characteristics was not given. Change in weight from baseline was not reported. Mortalities and SAEs were not documented. Total AEs: BDFZ 1.25 (8 patients), 2.5 (14 patients), 5 (12 patients), 10 mg/d (24 patients) and placebo (9 patients) |
| Industry sponsorship | Unclear risk | Sponsor not reported |