Burris 1990.
| Methods | Randomized, double‐blind, placebo‐controlled trial. Wash‐out period 4 to 6 weeks. Multicenter, conducted in USA | |
| Participants | Supine DBP 95 to 110 mmHg. Patients 18 to 70 years. Mean age 52 years. Males 62%. Baseline supine BP was 151.6/99.4 mmHg. The majority of patients were male (62%) with an average weight of 94 kg, indicating that they were obese | |
| Interventions | Diltiazem SR 60 mg (N = 15), 90 mg (N = 15), 120 mg (N = 15) or 180 mg bid (N = 15), diltiazem 60 mg, 90 mg, 120 mg or 180 mg bid + HCTZ 6.25 mg, 12.5 mg or 25 mg bid (all combined, N = 180), HCTZ 6.25 mg (N = 15), 12.5 mg (N = 15) or 25 mg bid (N = 15), or placebo (N = 15) Treatment duration = 6 weeks | |
| Outcomes | Change from baseline in trough mean supine DBP (primary) and SBP (secondary); heart rate, ECG, serum biochemistry, liver function | |
| Notes | A sample size calculation was provided based on 15 patients per treatment group to detect a difference in DBP reduction of 4 mmHg (SD ± 7.5 mmHg) between treatments (combination therapy versus HCTZ monotherapy) at a power of 94%. The study authors stated that there were no statistically significant differences across treatment groups in the baseline patient demographics and characteristics. 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, factorial‐design, placebo‐controlled, parallel‐group, multicenter study..." (line 1 under "Methods‐Study Design" p.1508). "...qualifying patients were randomised to a 6‐week double‐blind treatment phase..." (line 19 under "Methods‐Study Design" p.1508) 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 | Unclear risk | "This was a randomised, double‐blind, factorial‐design, placebo‐controlled, parallel‐group, multicenter study..." (line 1 under "Methods‐Study Design" p.1508). "...qualifying patients were randomised to a 6‐week double‐blind treatment phase..." (line 19 under "Methods‐Study Design" p.1508) Comment: no further information was given |
| Incomplete outcome data (attrition bias) All outcomes | Low risk | The efficacy analysis was based on an intention‐to‐treat technique Exclusions: 127/424 (30%) of patients were excluded from the study during the single‐blind placebo run‐in period prior to randomization Attrition: 36/297 (12%) of patients withdrew from the study for the following reasons: 10 patients for "intolerable side effects from medication", 7 for "inadequate BP control", 19 for "administrative reasons". Data were pooled, therefore it could not be determined from which treatment groups the patients originated WDAEs: 2% of patients from all HCTZ groups (6.25, 12.5 and 25 mg) combined. Reasons were not specified |
| Selective reporting (reporting bias) | High risk | SBP, heart rate, ECG, body weight, hematology, liver function and serum biochemical values (except for serum glucose and cholesterol levels) were measured, but not reported at endpoint of the study. Variability in DBP was not given. Effects of HCTZ 6.25, 12.5 and 25 mg on DBP at time points between week 0 and 6 were not shown. Mortality: none; SAEs: not given; and total AEs were not reported only those related to treatment. Reporting of AEs was incomplete |
| Industry sponsorship | High risk | The study was supported by grants and statistical services provided by Marion Laboratories |