Goldberg 1989.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel groups). 3 x 4 factorial design. Wash‐out period = up to 4 weeks on placebo followed by another 4 weeks "qualification phase". Multicenter, conducted in USA | |
| Participants | DBP 95 to 110 mmHg. Mean age 53.6 years. Males 52%. Baseline BP was 151.0/99.9 mmHg. Heart rate 74.1 bpm | |
| Interventions | Pinacidil 12.5 mg (N = 30), 25 mg (N = 34) or 37.5 mg bid (N = 32), pinacidil 12.5 mg, 25 mg or 37.5 mg bid + HCTZ 12.5 mg or 25 mg bid (N = 190, all combinations), HCTZ 12.5 mg (N = 34) or 25 mg bid (N = 33) or placebo (N = 31) Duration of treatment = 8 weeks | |
| Outcomes | Change from the baseline in trough mean supine and standing SBP and DBP; heart rate, body weight; hematology, urinalysis, serum biochemistry, pinacidil and HCTZ plasma concentrations | |
| Notes | Sample size calculation was not provided. The study authors stated that there were no significant differences across treatment groups in the baseline patient characteristics (line 3 under "Results" p.213). Supine BP in graphical form. Mortalities, SAEs and total AEs were not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Low risk | "...a randomised, double‐blind, 4 x 3 factorial, modified fixed‐dose multicenter trial." (see abstract p.208) "...patients were randomly allocated to one of 12 treatments in blocks of 12." (line 15 from top of p.209, left column) Comment: no further information was given. |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Low risk | "...a randomised, double‐blind, 4 x 3 factorial, modified fixed‐dose multicenter trial." (see abstract p.208) "At entry into the study, a placebo was prescribed for all patients (one capsule bid, identical in appearance to eventual double‐blind capsules)." (line 8 under "Study design p.209). No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Efficacy and safety analysis was based on an ITT technique Exclusions: 205/589 (35%) of patients were excluded from study during the placebo run‐in period before randomization Attrition: 87/384 (22.7%) of patients withdrew early from the study of which 9.1% withdrew for "failure to report, protocol violation, or physician/patient decision." The number of withdrawals from each treatment group was not given WDAEs: HCTZ 12.5 mg bid = 1/34 (2.9%) for "other reasons", HCTZ 25 mg bid = 1/33 (3%) for "other reasons" and placebo = 2/31 (6.5%) 1 ‐ weight gain, 1 ‐ "other reasons" |
| Selective reporting (reporting bias) | High risk | Standing SBP and DBP were measured but not reported. Supine SBP and DBP is shown in graphical form only (no standard deviations shown in graph). All‐cause mortality, SAEs and total AEs were not documented |
| Industry sponsorship | High risk | Supported by Eli Lilly and Company |