Frishman 1995.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 to 6 weeks. Multicenter, conducted in USA | |
| Participants | Sitting DBP 95 to 115 mmHg. Mean age: not given. % patients < 60 years: HCTZ 25 mg group = 61% versus placebo = 69%. Males: HCTZ 25 mg = 62% versus placebo = 64%. Non‐black race: HCTZ 25 mg = 84% versus placebo = 80%. Baseline sitting BP was 151/101 mmHg in HCTZ 25 mg group and 152/100 in placebo group. Sitting heart rate = 76 versus 75 |
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| Interventions | Bisoprolol 5 mg/d (N = 158), bisoprolol 5 mg/d + HCTZ 6.25 mg/d (N = 160), HCTZ 25 mg/d (N = 148) or placebo (N = 81) Trial duration = 4 weeks | |
| Outcomes | Mean change from baseline in trough sitting DBP and SBP at 3 and 4 weeks; analyses of the effects of age, sex, race, smoking status and baseline sitting DBP on change in BP; response rates; serum biochemistry | |
| Notes | A sample size calculation was provided based on 120 patients in each treatment group and 60 patients in the placebo group to detect a difference of at least 2.5 mmHg between active treatments and 3.1 mmHg between active treatment and placebo with 80% power. The study authors stated that there were no statistically significant differences across treatment groups in the baseline patient demographics and characteristics. SD for BP data (change from baseline) not given; it was reported as SE | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "This was a multicenter, randomised, placebo‐controlled, parallel‐group study..." (line 1 under "Methods‐Study Design" p.183). Eligible patients were randomized to treatment (see line 9 under "Methods‐Study Design" p.183). No further information was given |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "This was a multicenter, randomised, placebo‐controlled, parallel‐group study...followed by a 4‐week double‐blind treatment period..." (line 1 under "Methods‐Study Design" p.183). Eligible patients entered the 4‐week, double‐blind treatment period (line 20 from top of p.183). No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | Efficacy analysis was based on an ITT technique Exclusions: the number of patients who were excluded from the study during the single‐blind, placebo run‐in period prior to randomization was not given Attrition: 38/547 (7%) patients were not included in the BP analysis. It is not known how many patients withdrew from the study and for what reasons WDAEs: 9/547 (1.6%) patients withdrew due to "clinical adverse experiences" for the following reasons: 7 ‐ "related to underlying medical conditions or concomitant illness" and 1 ‐ "bradycardia" and 1 ‐ "impotence". 2 other patients withdrew due to "laboratory findings" (not clearly explained). Note that the WDAE data were pooled, not presented as separate for each treatment group |
| Selective reporting (reporting bias) | High risk | Heart rate was measured but not reported at the end of the study. ECG, a vital sign, was not reported. Variability in metabolic data was not reported. Glucose levels were measured but not reported All‐cause mortality and SAEs were not documented. Total AEs were not reported; drug‐related "adverse experiences" were |
| Industry sponsorship | High risk | Supported by a grant from American Cyanamid Company |