Weir 1992.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 to 6 weeks. Multicenter, USA | |
| Participants | Supine DBP 95 to 110 mmHg. Mean age 53.5 years. Males 65%. Baseline BP 152.6/99.8 mmHg in HCTZ group and 152.7/99.5 mmHg in placebo group | |
| Interventions | Diltiazem SR 60 mg, 90 mg or 120 mg bid (all combined, N = 72), diltiazem SR 60 mg, 90 mg or 120 mg bid + HCTZ 6.25 mg or 12.5 mg bid (all combined, N = 75), HCTZ 6.25 mg or 12.5 mg bid (all combined, N = 76), or placebo (N = 75) Trial duration = 12 weeks (3 consecutive 4‐week treatment periods; 1st 8 weeks of data available) | |
| Outcomes | Change from baseline in mean trough standing and supine DBP and SBP (at weeks 4, 8 and 12); BP response rate; heart rate, ECG and serum biochemistry | |
| Notes | A sample size calculation was not provided. Patients in the 6.25 mg indapamide group were subjected to forced titration to 12.5 mg indapamide 8 weeks into DB treatment. Therefore, data after 8 weeks were excluded from the review. The study authors stated that the baseline patient demographics and characteristics (i.e. age, race, smoking status, height and body weight) were similar across treatment groups except for gender. All patients receiving the HCTZ 6.25 mg bid dose were force‐titrated to HCTZ 12.5 mg bid after 8 weeks. Mortalities, SAES and total AEs were not reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "This was a randomised, double‐blind, placebo‐controlled, parallel‐group, multicentre study comparing various doses of DTZ SR/HCTZ combination therapy with DTZ SR and HCTZ monotherapies and placebo... " (line 1 under "Methods‐Study Design" p.134). "...qualifying patients were randomised to a 12‐week double‐blind treatment phase..." (line 13 under "Methods‐Study Design" p.134). 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 | "...qualifying patients were randomised to a 12‐week double‐blind treatment phase..." (line 13 under "Methods‐Study Design" p.134). No further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Unclear risk | The primary efficacy analysis was based on an intention‐to‐treat (ITT) technique with the LOCF (last observation carried forward) Exclusions: 115/413 (28%) of patients were excluded from the study during the placebo run‐in period prior to randomization Attrition: 44/298 (15%) of patients withdrew from the study. Reasons given included "intolerable side effects" and "inability to control BP", however these 2 reasons did not account for all patients withdrawing. Specific reasons were not given and from which group the patients originated is not known WDAEs: if assumed to be equivalent to "intolerable side effects", there were 6 patients from the HCTZ group and 2 from the placebo group who withdrew due to adverse events. Specific reasons were not given |
| Selective reporting (reporting bias) | High risk | ECG was not reported at the study's endpoint. BP data were available in graph form only. SE (not SD) was included in mean BP change. Mortalities, SAEs, total AEs were not documented. Treatment‐related AEs were reported |
| Industry sponsorship | High risk | Funded by research grant from Marion Merrell Dow Inc. |