| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Conducted in USA |
| Participants |
DBP 95 to 110 mmHg. Mean age 50.2 years. Males 40%. Baseline BP was 150.2/100.1 mmHg in the treatment group and 149.8/99.6 in the control group |
| Interventions |
Indapamide 1.25 mg daily (N = 98) or placebo (N = 97)
Trial duration = 8 weeks |
| Outcomes |
Change from the baseline in trough mean sitting and standing SBP and DBP (at 2, 4, 6 and 8 weeks); response rate; heart rate, ECG, hematology, urinalysis, serum biochemistry, body weight, vital signs |
| Notes |
A sample size calculation was not provided. Baseline patient characteristics did not include medical history. The study authors did not state whether there were statistically significant differences between indapamide and placebo groups with regard to baseline patient demographics and characteristics. Standard error (SE) given for BP data. SD or SE not given for biochemical data |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"Patients who met the entry criteria were randomised at the end of a four week single‐blind placebo wash‐out period to either 1.25 mg indapamide or placebo..." (line 1 under "Design" p.572). No further information about sequence generation was given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
"Three of the [indapamide] patients received potassium supplements concomitant with double‐blind medication." (line 8 p.575). This could have broken the blinding. Blinding not explicitly stated by study authors |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
Not known whether efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique, however sitting SBP results were based on the "all‐treated population..." (line 22 from top p.573)
Exclusions: number of patients excluded from the study during the placebo run‐in period prior to randomization was not given
Attrition: 16/98 (16%) and 7/97 (7%) of patients from the indapamide and placebo groups, respectively, withdrew from the study. Reasons for withdrawals included (IND versus PLB): 8 ‐protocol violations, 3 ‐ treatment failures, 3 ‐ clinical adverse experiences, 1 ‐ withdrawal of consent and 1 ‐ lost to follow‐up versus 2 ‐ clinical adverse experiences, 2 ‐ lost to follow‐up, 1 ‐ protocol violation, 1 ‐ treatment failure and 1 ‐ other reasons
WDAEs: withdrawals due to "clinical adverse experiences" included: IND group, 3/98 (3.1%) versus placebo group, 2/97 (2.1%) for the following reasons: (rash + abnormal ECG), (dizziness) and (dizziness + headache + nausea + vomiting + photophobia + hypertension) versus (breast carcinoma) and (headache) |
| Selective reporting (reporting bias) |
High risk |
Baseline sitting BP did not include SD or SE; change in sitting BP was reported at endpoint with SE. Variability was not reported for baseline patient characteristics or biochemical data. Baseline standing BP was measured but not reported. Change in heart rate, serum sodium and chloride levels, hematology, urinalysis, vital signs, weight and ECG were measured but not reported at endpoint. Mortalities and SAEs were not clearly documented. Total AEs: 54/98 (55%) patients in indapamide group and 46/97 (47%) in the placebo group. A list of AEs (with description of event) occurring in at least 3% of patients was included |
| Industry sponsorship |
High risk |
Received grants from General Research Support of the School of Public Health, University of Minnesota and from Merck Sharp & Dohme |
