Capone 1983.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 6 weeks. Multicenter, conducted in USA | |
| Participants | DBP 95 to 114 mmHg. Mean age 52 years. Males 66%. Baseline BP was 152/102.8 mmHg in the treatment group and 153/103.8 in the control group | |
| Interventions | Indapamide 1.0 mg (N = 24), 2.5 mg (N = 23) or 5.0 mg/d (N = 23) or placebo (N = 22) Trial duration = 8 weeks (+ 2 weeks of single‐blind follow‐up) | |
| Outcomes | Standing and supine SBP and DBP (taken at 2‐week intervals); response rate; pulse rate, ECG, body weight, serum biochemistry and urinalysis | |
| Notes | Primary efficacy analysis not stated by study authors. A sample size calculation was not provided. Baseline patient demographics, measurements and other variables were similar across all treatment groups (P value = NS). BP data in graph form only (see Fig. 2 and 4, p.310‐311) with no SD. No SD for metabolic data and number of subjects not provided. Mortalities, SAEs and WDAEs were not explicitly reported | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "The study was conducted according to a randomised, double‐blind, parallel design with four groups receiving once‐daily dosages of placebo or 1mg, 2.5 mg, or 5 mg indapamide. Equal numbers of patients were randomly assigned to each of the four treatment groups." (line 1 under "Methods" p.307). Technique for sequence generation not stated explicitly by study authors |
| Allocation concealment (selection bias) | Unclear risk | Not stated by study authors |
| Blinding (performance bias and detection bias) All outcomes | Unclear risk | "The study was....double‐blind..." (line 1 under "Methods" p.307). No further information on blinding was given |
| Incomplete outcome data (attrition bias) All outcomes | High risk | It is not known whether study was based on an ITT or per‐protocol technique
Exclusions: number of patients excluded from study after the single‐blind placebo run‐in period and before randomization was not reported
Attrition: there were 4/92 (4.3%) patient withdrawals for dizziness (IND 2.5), pancreatitis (IND 1.0), lack of therapeutic response (PLB), and dizziness + lack of response (PLB). In addition, 5/92 (5.4%) patients were excluded from the evaluation of the efficacy of indapamide due to various reasons including poor compliance and headaches (IND 1.0 mg group), increased hypertension (PLB), a stomach lesion (IND 5.0), concomitant use of phenytoin (IND 2.5 mg) and rash (IND 5.0 mg), however, it is not known whether any of these 5 patients were amongst the 4 patients who eventually withdrew WDAEs were not stated explicitly by study authors (but based on information in the results section of the study it was presumed to be: 2 patients from the IND 1.0 mg group, 1 from IND 2.5 mg group, 2 from IND 5.0 and 2 from the placebo group) |
| Selective reporting (reporting bias) | High risk | Baseline patient demographics and characteristics were not reported. Weight and pulse were measured but not reported. BP data were graphed in figures only. No standard deviations (SD) for BP or metabolic data were given. Study authors did not comment on all‐cause mortality, and SAEs and WDAEs were not clearly stated. AEs, regardless of relationship to study drug were not reported. Only drug‐related AEs were reported; for each treatment group there were: PLB = 1/22 (4.5%), IND 1.0 = 4/24 (17%), IND 2.5 = 6/23 (26%) and IND 5.0 = 6/23 (26%) |
| Industry sponsorship | Unclear risk | Sponsor not reported |