| Methods |
Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period = 4 weeks. Multicenter, conducted in USA |
| Participants |
Standing DBP 90 to 109 mmHg. Mean age 53.6 years. Males 58%. Baseline BP was 146.1/97.2 mmHg in the treatment group and 145.3/95.8 mmHg in the control group |
| Interventions |
Chlorthalidone 12.5 mg (N = 20), 25 mg (N = 20), 50 mg (N = 20), 75 mg/d (N = 20) or placebo (N = 20)
Treatment duration = 12 weeks |
| Outcomes |
Mean standing and supine SBP and DBP (Korotkoff sounds 4 and 5 reported for DBP) at baseline and end of treatment; BP response rate; ECG; serum biochemistry, urinalysis and body weight |
| Notes |
A sample size calculation was not provided. Patients were excluded based on a disability, geographic location, poor motivation, psychosis and other restrictive criteria which surpassed those of similar trials investigating the BP lowering of thiazides. The mean BP at endpoint was calculated by taking the average of BP readings at the 3 last treatment visits. Normally endpoint measurements are taken from the last evaluable time point in the study. The study authors stated that the baseline patient demographics and characteristics (i.e. BP, body weight and serum biochemical values) were similar across treatment groups (P value = NS). Korotkoff phase 5 was used for determining DBP in this review. Mortalities and SAEs not reported |
| Risk of bias |
| Bias |
Authors' judgement |
Support for judgement |
| Random sequence generation (selection bias) |
Unclear risk |
"...patients were randomly and in a double‐blind fashion placed on one of the following 5 regimens of medication..." (line 7 from bottom of p.193). 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 |
"...patients were randomly and in a double‐blind fashion placed on one of the following 5 regimens of medication taken once daily replacing an identical‐appearing placebo used in the placebo run‐in period..." (line 7 from bottom of p.193) |
| Incomplete outcome data (attrition bias)
All outcomes |
Unclear risk |
It is not known if primary efficacy analysis was based on an intention‐to‐treat (ITT) or per‐protocol technique
Exclusions: the study did not report how many, if any patients were excluded from the study during the placebo run‐in period prior to randomization
Attrition: a total of 6/100 (6%) patients withdrew from the study, this included 3/20 (15%) from the chlorthalidone 50 mg group: 2 patients for "adverse reactions" and 1 for "treatment failure"; 1/20 (5%) from the chlorthalidone 75 mg group for "adverse reactions"; and 2/20 (10%) patients from the placebo group for "treatment failure" and "prolonged hospitalization for low back pain"
WDAEs: 3/100 (3%) patients withdrew due to what study authors referred to as "adverse reactions" (presumed to be adverse events); 2 from the chlorthalidone 50 mg group for "rash" and "severe headaches" and 1 from the chlorthalidone 75 mg for "orthostatic hypotension" |
| Selective reporting (reporting bias) |
High risk |
Heart rate, ECG and urinalysis were measured but not reported on in the study. Variability was not included in baseline patient demographics and characteristics; medical history of patients was not reported. BP and biochemical (i.e. serum potassium, uric acid and glucose) data were expressed as baseline and endpoint averages, not as change from baseline; in addition, SE (standard error of mean), not SD, was given. Baseline weight and serum chloride levels were measured, but the study only reported the mean change from baseline. Mortalities and SAEs were not stated explicitly. Total AEs: in the chlorthalidone 12.5, 25, 50 and 75 mg groups: 3 (15%), 6 (30%), 7 (35%) and 7 (35%) patients; and in the placebo group: 3 patients (15%) |
| Industry sponsorship |
Unclear risk |
Sponsor not reported |
