Curry 1986.
| Methods | Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out period ≤ 4 weeks. Multicenter, conducted in USA | |
| Participants | Sitting DBP 90 to 110 mmHg. Age range: 30 to 71 years. Males 43%. 59% Black race. Baseline BP 146 to 154/97 in the 3 treatment groups and 151/99 in the control group | |
| Interventions | Metolazone 0.5 mg (N = 26), 1 mg (N = 25), 2 mg/d (N = 27) or placebo (N = 27) Treatment duration = 6 weeks | |
| Outcomes | Sitting and standing SBP and DBP (at 2‐week intervals); response rate; ECG, hematology, serum biochemistry and urinalysis | |
| Notes | A sample size calculation was not provided. Anomalously high DBP response (‐31 mmHg) from 1 patient in the placebo group increased the mean and variability in that group substantially enough to lessen the magnitude of statistical difference compared to active treatment (analysis was done including this outlier patient). There were no significant differences between treatment groups in baseline demographics. Medical history was not included in baseline characteristics. All AE data grouped together. Detailed reporting of biochemical data restricted to potassium levels only. Mortalities, SAEs and total AEs were not reported. Publication consisted of 2 studies (the positive‐controlled study did not include a placebo arm, therefore this study will not be discussed further in this review) | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Random sequence generation (selection bias) | Unclear risk | "In the placebo‐controlled study, patients were randomly assigned to receive single daily doses of placebo, or 0.5, 1.0, or 2.0 mg of...metolazone." (line 3 under "Drugs" p.49). 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 | "...a double‐blind, parallel clinical [study]" (line 17 from top under "Introduction" p.48). No further information given of how the study was blinded |
| Incomplete outcome data (attrition bias) All outcomes | High risk | Not known whether efficacy analysis was based on an ITT or per‐protocol technique
Exclusions: 43/148 (29%) of patients were excluded from the study during the placebo run‐in phase prior to randomization Attrition: 7/105 (6.7%) of patients withdrew from the study. Reasons for withdrawals included: 1 ‐ voluntary withdrawal, 4 ‐ increased blood pressure and 2 ‐ missed visit WDAEs: 0/105 (0%) of patients withdrew due to adverse events (termed "adverse experiences"), however the precise reasons were not given. Note: data from each treatment group were pooled (not presented separately) |
| Selective reporting (reporting bias) | High risk | Except for potassium levels, the following were measured but not reported on: serum hematology, glucose, lipids, electrolytes, ECG and urinalysis. Mean and SD for baseline patient demographics and characteristics were not given. Mortalities, SAEs and total AEs were not documented (see line 1 under "Adverse Experiences" p.55) |
| Industry sponsorship | Unclear risk | Sponsor not reported |