| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 6 weeks. Johannesburg, South Africa |
| Participants |
DBP 95 to 115 mmHg. Mean age 61 years. Males 7%. Baseline standing BP was 157/96 in the treatment group and 158/96 in the control group |
| Interventions |
Indapamide 2.5 mg/d or placebo. N = 35 randomized
Trial duration = 8 weeks (followed by another 8 weeks of magnesium chloride added onto IND or PLB in patients with low serum potassium levels; not discussed in this review) |
| Outcomes |
Mean standing and supine SBP and DBP at weeks 4, 8, 12 and 16; heart rate; body weight, serum biochemistry; RBC Na+, K+ and Mg2+
|
| Notes |
Incomplete reporting of total withdrawals. WDAEs, mortalities, SAEs and total AEs were not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"....patients were randomly allocated, in double‐blind fashion, to indapamide 2.5 mg daily or matching placebo." (line 2 under "Trial Design" p.274). No further information given |
| Allocation concealment (selection bias) |
Unclear risk |
Not stated by study authors |
| Blinding (performance bias and detection bias)
All outcomes |
Unclear risk |
No further information given on how blinding was achieved. "After 7 weeks both groups received magnesium chloride presented as enteric‐coated slow‐release 535 mg tablets, taken in two doses, 3 at breakfast and 3 at dinner, for a further 8 weeks." (line 6 under "Trial Design" p.274). It was further stated that, "Although magnesium chloride was not given in double‐blind form it appears to have had no additive effect, either alone or with indapamide, on the blood pressure in these elderly patients with mild hypertension." (line 6 from bottom p.276). Comment: adding another active medication at the midpoint of the trial could have compromised patient blinding. Some patients, those with low serum potassium levels, were administered supplemental potassium medication |
| Incomplete outcome data (attrition bias)
All outcomes |
High risk |
The study authors did not state whether the primary efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique
Exclusions: it is not known if any patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: 8/35 (23%) of patients withdrew from the study, 2 ‐ "tachycardia", 4 ‐ "developed diastolic pressure > 115 mmHg (1 ‐ indapamide, 3 ‐ placebo) and 2 ‐ "left for domestic reasons."
WDAEs: not given |
| Selective reporting (reporting bias) |
High risk |
Heart rate, serum creatinine, calcium, uric acid and hematology were measured but not reported on at the end of the study. Results were expressed as mean ± SEM. Mortalities, SAEs and total AEs were not reported |
| Industry sponsorship |
High risk |
Supported by Servier Laboratories SA (Pty) Ltd and the South African Medical Research Council |
