Prisant 2000.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Multicenter, USA | |
| Participants | Supine DBP 95 to 114 mmHg. Mean age 51.6 years. Males 60%. Baseline BP was 156.7/101.8 mmHg in the indapamide 2.5 mg group and 153.4/100.5 mmHg in the placebo group | |
| Interventions | Diltiazem XR 120 mg, 180 mg, 240 mg, or 360 mg/d (all combined, N = 187), diltiazem XR 120 mg, 180 mg or 240 mg/d + indapamide 1.25 mg or 2.5 mg/d (all combined, N = 75), indapamide 1.25 mg (N not reported) or 2.5 mg/d (N = 24), or placebo (N = 43) Trial duration = 6 weeks | |
| Outcomes | Change from baseline in mean trough supine SBP and DBP; 24‐hour ambulatory BP (using an automated monitoring device); ECG, hematology, urinalysis, serum biochemistry | |
| Notes | A sample size calculation was not provided. The small sample in the indapamide treatment group could have biased the results. Forced‐titration schedule for all patients assigned to receive non‐thiazides in the 1st week of DB treatment. Female patients were in the majority in the placebo group (60%), but in the minority in the indapamide 2.5 mg group (25%). Study authors stated that baseline patient demographics of age, race and gender were "evenly distributed" across treatment groups. Study does not report on the patient group receiving 1.25 mg/d indapamide due to large variability relative to effect. Total withdrawals and total AEs not given. |
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| 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, multicenter study in patients with mild to moderate hypertension. After 4 weeks on single‐blind placebo treatment, qualifying patients were randomly assigned to double‐blind medication." (line 1 under "Methods‐Study Design" p.178). 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 | "Blinding was achieved by placing diltiazem XR tablets and indapamide powder in capsules, which were identical in appearance, size, shape and colour to those of their respective placebos. Each patient took three capsules of medication once a day in the morning." (line 11 under "Methods‐Study Design" p.178) |
| Incomplete outcome data (attrition bias) All outcomes | High risk | It was not stated whether the primary efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique Exclusions: the number of patients excluded from the study during the placebo run‐in period prior to randomization was not given. However, because of the high variability in the BP effect in patients receiving indapamide 1.25 mg/day, this treatment arm was excluded from the analysis of results (presumed to be an N = 67 patients) Attrition: not given WDAEs: 29 (7.3%) patients withdrew due to adverse events (referred to by the authors as "adverse clinical events"). The specific reasons were not given and no details were given as to which treatment groups the patients originated from |
| Selective reporting (reporting bias) | High risk | Serum chemistry (except potassium and uric acid levels), hematology, urinalysis and ECG were measured, but actual values were not reported on at endpoint. Statistical analysis of the effects of indapamide on ambulatory 24‐hour BP changes was not performed. Study authors removed patients in the indapamide 1.25 mg treatment group from analysis due to large variability effect in that group. Variability in BP data was not given. Mortalities: None. SAEs: 17 patients (treatment group not specified and reasons not given). Total AEs not reported. There was no detailed list of each AE patients experienced. |
| Industry sponsorship | High risk | study was sponsored by manufacturer |