Frei 1994.

Methods	Randomized, double‐blind, placebo‐controlled trial (parallel arms). Wash‐out (placebo run‐in) period = 4 weeks. Multicenter, Germany
Participants	DBP 95 to 114 mmHg and SBP ≤ 240 mmHg. Mean age: 55.1 years. Males: 50%. Baseline BP was 166/103 mmHg in the HCTZ 25 mg treatment group and 166/102 in the placebo group. Pulse pressure was not reported
Interventions	Moxonidine 0.4 mg/d (N = 38), moxonidine 0.4 mg/d + hydrochlorothiazide 25 mg/d (N = 42), hydrochlorothiazide (HCTZ) 25 mg/d (N = 40) or placebo (N = 41) Treatment duration = 8 weeks
Outcomes	Mean change from the baseline in sitting DBP and SBP; responder rates; blood and urine lab tests
Notes	Sample size calculation was not provided. Patients were permitted to take medication for diseases unrelated to hypertension which is contrary to what most other studies investigating the BP‐lowering effects of thiazides allow. Most other studies either restrict or ban and monitor any use of other medications during the study. Details were not provided. Patients with more serious SBP levels as high as 240 mmHg were permitted to enter the study. The study authors did not state whether there were statistically significant differences between HCTZ and placebo treatment groups in baseline patient demographics and characteristics. Biochemical data measured but not reported. Total AEs not given
Risk of bias
Bias	Authors' judgement	Support for judgement
Random sequence generation (selection bias)	Unclear risk	"The study was designed as a multicenter, double‐blind, placebo‐controlled, parallel‐group, prospectively randomised study..." (line 23 under "Subjects and Methods" p.S26). No further information was given
Allocation concealment (selection bias)	Unclear risk	Not stated by study authors
Blinding (performance bias and detection bias) All outcomes	Unclear risk	"The study was designed as a multicenter, double‐blind, placebo‐controlled, parallel‐group, prospectively randomised study..." (line 23 under "Subjects and Methods" p.S26)
Incomplete outcome data (attrition bias) All outcomes	Low risk	Efficacy analysis was based on an intention‐to‐treat (ITT) technique Exclusions: 14/177 (8%) of patients were excluded from the study during the placebo run‐in period prior to randomization Attrition: 3 patients (3/163 = 1.8%) were not included in the efficacy analysis of the ITT population: 2 patients did not take study medications following randomization and 1 patient was without a post‐baseline measurement. It is not known from which treatment groups these patients came WDAEs: 4/161 (2.5%) of patients withdrew due to adverse events, 1 patient from the placebo group for headache and the remaining 3 from other treatment groups other than the HCTZ 25 mg group (note: safety data were based on an ITT group of 161 patients)
Selective reporting (reporting bias)	High risk	Baseline patient demographics and characteristics did not include weight or vital signs and variability was omitted. Biochemical data were measured but not reported. Mortalities and SAEs were not explicitly stated by study authors. Total AEs were not reported, only the most commonly occurring AEs were included (but no systematic approach to reporting them was taken)
Industry sponsorship	Unclear risk	Sponsor not reported