| Study | Reason for exclusion |
|---|---|
| Amery 1978 | EPWHE study. Combination of 25 to 50 mg HCTZ with triamterene. Exclusion criteria met |
| Anavekar 1979 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). There is no parallel placebo treatment arm |
| Bateman 1979 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. Also there was no wash‐out period in between treatment periods. 1st 4 weeks' data useful but not available. Chlorthalidone 25 mg versus placebo |
| Batterman 1966 | Publication includes 110 trials in 62 patients which used both randomized and double‐blind methods. Blood pressure measurements were not taken under resting condition but determined as soon as the patients were seated |
| Blaufox 1992 | There is no mention of whether this RCT was double‐blinded |
| Boike 1982 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Borghi 1993 | No mention if trial was blinded. Data available only from 6 months onwards. BP and biochemical data from hypertensive patients were not reported separately from those of normotensive patients |
| Carretta 1988a | A single‐blinded, cross‐over trial. Indapamide 2.5 mg versus placebo for 3 months. There was no wash‐out between cross‐over treatment so data from 1st 3 months useful but not available |
| Carretta 1988b | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Chalmers 1976 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Chalmers 1982 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Chalmers 1986 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Christiansen 1981 | Randomized, double‐blind, placebo‐controlled trial. Bendroflumethiazide 5 mg/day versus placebo. Patients were all healthy, postmenopausal women (selection of patients was not based on blood pressure, except if > 170/105 mmHg) |
| Consoli 1985 | Foreign language (Italian). No placebo treatment arm |
| Cranston 1962 | Although it is a double‐blind RCT in 10 patients randomized to chlorthalidone 50 mg/day or placebo, data are available at week 27 and not between 3 and 12 weeks |
| Crowe 1987 | There was a placebo wash‐out period prior to randomization but no parallel placebo treatment arm |
| Datta 1989 | Randomized, double‐blind, placebo‐controlled trial. BP data reported at baseline and 24 weeks. Data requested but not available for other time points in between. The author is deceased |
| Davis 1993 | Subgroup of TAIM study. The TAIM study is a double‐blind RCT. Patients were randomized to placebo, chlorthalidone 25 mg/day or atenolol 50 mg/day. However, the dose was titrated only in non‐responders from 2 weeks onwards |
| Dean 1971 | Although randomized patients to HCTZ and placebo there is no mention of a wash‐out period before randomization |
| Durel 1992 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Eames 2005 | Randomized, double‐blind, placebo‐controlled trial. Bendrofluazide 2.5 mg/d versus placebo. Study duration was 7 days |
| Elliot 1991 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). Indapamide 1.25 mg, HCTZ 25 mg/day or placebo for 4 weeks. No wash‐out between treatments. 1st 4 weeks' data not available |
| Erwteman 1984 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Fagard 1976 | No mention if trial was randomized. In addition to patients with essential hypertension there were 7 with renovascular hypertension and 5 with renal parenchymal hypertension, however separate data for these 3 groups of patients were not available |
| Fernandez 1980 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Flack 2001 | Multicentre randomized, double‐blind, placebo‐controlled trial. Combination therapy consisting of hydrochlorothiazide and losartan versus placebo. HCTZ monotherapy treatment arm absent |
| Gall 1992 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). No wash‐out phase between cross‐over. 12.5 mg/day in 1st 4 weeks after which the dose was doubled in non‐responders only. Therefore, only 1st 4 weeks' data useful but not available |
| Galloway 1974 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. Cross‐over without a wash‐out period in between treatment. 1st 4 weeks' data useful but not available. Bendrofluazide 2.5 mg or placebo for 4 weeks. DBP recorded by phase IV muffle sound |
| Gerber 1985 | This is a single‐blinded RCT and is therefore excluded |
| Gleerup 1996 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). HCTZ 24 mg versus placebo. Since no wash‐out period before cross‐over, data from 1st 4 weeks useful but not available |
| Goldman 1980 | VA study. Randomized, double‐blind, placebo‐controlled trial. Baseline inclusion 85 to 105 mmHg; since mean DBP > 90 mmHg, inclusion was justified. Chlorthalidone 50 mg/day versus placebo. Step 1 data useful. At step 2, dose was doubled in non‐responders only. Data given at the end of 1 year and not the required 3 to 12‐week window |
| Grimm 1981 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Grimm 2002 | Randomized, double‐blind, placebo‐controlled trial. Chlorthalidone 15 mg/day versus placebo. 15 mg dose of CTD was doubled to 30 mg/day in non‐responders only. Also, BP data was not reported separately for the 2 CTD doses |
| Hobbs 1964 | Randomized, double‐blind placebo controlled trial that meets the criteria but provides only mean BP data. Data for SBP and DBP were not provided |
| Horvath 1979 | Bendrofluazide versus placebo in 18 patients with a treatment period of 8 weeks' duration. No wash‐out period. The 1st 8 weeks' data useful but not available. Also BP recorded as mean arterial pressure |
| Jackson 1986 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). HCTZ + amiloride combination was used therefore the trial was excluded. There was no thiazide monotherapy arm |
| Jain 1985 | All patients were started on chlorthalidone 25 mg/day open‐label for 2 weeks and then randomized to added therapy with either guanfacine or clonidine. There was no parallel placebo arm |
| Johnson 1986 | Randomized, double‐blind, placebo‐controlled trial. A cross‐over trial without a wash‐out period between treatment. Data needed from the 1st 4 weeks but not available. HCTZ 100 mg/day versus placebo |
| Jueng 1987 | After 1 week of double‐blind therapy, dose of HCTZ was doubled (from 25 mg to 50 mg) in patients not responding to treatment (defined as a diastolic BP > 90 mmHg). Inclusion criteria not met |
| Koskelainen 1985 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Kuramoto 1981 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. 35/44 patients were treated with thiazide monotherapy (i.e. trichlormethiazide 1 to 4 mg), however the exact number of patients in each arm is not known. Data between weeks 3 and 12 are not reported |
| Kuramoto 1985 | Japanese language trial. No parallel placebo arm, therefore excluded |
| Lechi 1982 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Lutterodt 1980 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. A cross‐over trial without a wash‐out period in between treatment. 1st 12 weeks' data useful but not available. HCTZ 50 mg or placebo. N = 27 of which 16 were eliminated so more than 50% withdrawals. The remaining 11 patients completed the trial. Mean arterial pressure given. SBP or DBP not given |
| Materson 1993 | Randomized, double‐blind, placebo‐controlled trial. Inclusion DBP 95 to 109 mmHg. HCTZ 12.5 mg up to 50 mg/day. Dose titrated every 2 weeks until DBP < 90 mmHg was achieved or maximal pre‐determined dose reached (data, however, were not available in the 1st 4 weeks) |
| Maus 1978 | Foreign language trial (French). No placebo arm |
| Maximilian 1970 | Foreign language trial (Romanian) |
| McCorvey 1993 | Randomized, double‐blind, placebo‐controlled trial (cross‐over trial). No adequate drug wash‐out prior to randomization of patients to either enalapril, propranolol, HCTZ or placebo |
| Merrill 1987 | No placebo arm of study |
| Milliez 1975 | Randomized, double‐blind, placebo‐controlled trial (cross‐over design). Meets criteria but data not available. No wash‐out period in between treatment periods. 1st 6 weeks data useful but not available. Indapamide 5 mg or chlorothiazide 500 mg or placebo for 1 month. WDAE not given |
| Morgan 2001 | Randomized, placebo‐controlled trial. Trial not blinded |
| Moser 1986 | Trial not randomized |
| MRC Working Party 1983 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. Bendrofluazide 5 or 10 mg/day versus placebo. Also the number of patients taking 5 mg or 10 mg not specified |
| Muiesan 1987 | Randomized, placebo‐controlled trial. Single‐blinded, stepped‐up dosage for patients who did not respond after 4 weeks of double‐blind active treatment. Only patients with a DBP < 100 mmHg were permitted to enter a subsequent phase of double‐blind treatment |
| Myers 1982 | Randomized, double‐blind, placebo‐controlled trial. Meets criteria but data not available. Diuretic treatment arms combined together. No wash‐out period prior to double‐blind treatment |
| Myers 1983 | Randomized, double‐blind, placebo‐controlled trial (cross‐over trial). No wash‐out period prior to randomization of patients to double‐blind treatment and no drug wash‐out between treatment periods. It meets the criteria but data from 1st 6 weeks not available. HCTZ 50 mg versus placebo |
| Okun 1978 | Randomized, double‐blind, placebo‐controlled trial with 4 weeks wash‐out period. Ticrynafen 250 mg, HCTZ 50 mg or placebo for 6 weeks. Dose titrated after 2 weeks in patients whose BP did not decrease by more than 10 mmHg |
| Okun 1979 | Randomized, double‐blind, placebo‐controlled trial. Tienilic acid 250 mg, HCTZ 50 mg versus placebo. 2 weeks after randomization dose doubled in patients whose BP did not decrease by 10 mmHg. Does not meet inclusion criteria |
| PATS Col. Group 1995 | Randomized, double‐blind, placebo‐controlled trial. Indapamide 2.5 mg versus placebo. Patients included hypertensive and normotensive with history of a minor or major stroke (cut‐off values for baseline BP were not specified) |
| Petersen 1996 | Randomized, double‐blind, placebo‐controlled trial (a cross‐over trial). HCTZ 6 mg versus placebo. Since no wash‐out period before cross‐over, data from 1st 4 weeks useful but not available |
| Reisin 1997 | Randomized, double‐blind, placebo‐controlled trial where data from first 4 weeks after randomization, before dose was titrated in non‐responders could have been included. Author (Reisin) was contacted by email. He lost the data from this study in hurricane Katrina |
| Russel 1968 | Meets criteria but data not available. Randomized, double‐blind, placebo‐controlled trial cross‐over without wash‐out period in between treatment. 1st 6 weeks' data useful but not available. HCTZ 200 mg versus placebo |
| Safar 1994 | Although it meets the inclusion criteria, data are available only in poster format. Details of the study methodology not available and unable to grade quality of evidence |
| Salvetti 1969 | Randomized, double‐blind, placebo‐controlled trial (cross‐over design). Wash‐out phase between double‐blind treatment not mentioned. Inclusion DBP 101 to 114 mmHg. Chlorthalidone 25 mg/day or placebo for 1 month. Data for 1 month not available |
| Salvetti 1989 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Samson 1965 | Randomized, double‐blind, placebo‐controlled trial. Cross‐over design (3 treatment periods in each patient: chlorthalidone 100 mg/d, polythiazide 4 mg/d, placebo; duration of each period was 2 months ‐ no data between 3 and 12 weeks available). Also, there was no placebo run‐in period |
| Schaller 1985 | This trial, although double‐blind, does not mention whether patients were randomized to indapamide or placebo |
| Shahinfar 1999 | Double‐blind randomized controlled trial. There was no wash‐out period prior to randomization ‐ all patients received HCTZ |
| Shimizu 1977 | A foreign language RCT (Japanese). Non‐blinded in methodology, therefore excluded from this review |
| Siegel 1990 | Patients were withdrawn from diuretic treatment before entering study. Outcome is left ventricular hypertrophy (LVH) on ECG. No data on SBP, DBP or WDAEs |
| Stein 1992 | Dose‐ranging trial in 19 black patients. Each dose of 6.25 mg, 12.5 mg, 25 mg and 50 mg of hydrochlorothiazide or placebo given randomly for 6 weeks. No wash‐out between treatment periods. Data from 1st 6 weeks useful but not available |
| Stornello 1990 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| TOMHS 1991 | Randomized, double‐blind, placebo‐controlled trial. TOMHS (the Treatment Of Mild Hypertension Research) Group, USA. Trial excluded because dose of chlorthalidone was doubled from 15 mg to 30 mg daily in non‐responding patients only (defined as a diastolic BP ≥ 95 mmHg on 3 successive visits or ≥ 105 mmHg at a single visit). Data from the titrated group were not available separately Duplicate publications (e.g. Grimm Jr. JAMA,1996) |
| Valmin 1975 | Randomized, double‐blind, placebo‐controlled trial (cross‐over design). Meets criteria but data not available. No wash‐out period in between treatment periods. 1st 4 weeks' data useful but not available. Furosemide 12.5 mg, 25 mg, 40 mg, or HCTZ 25 mg or placebo for 4 weeks |
| Wassertheil‐Smoller 1992 | TAIM study is a double‐blind RCT with patients randomized to placebo, chlorthalidone 25 mg/day or atenolol 50 mg/day. However, dose was titrated in non‐responders only from 2 weeks onwards |
| Weber 1977 | Randomized, double‐blind, placebo‐controlled trial (cross‐over trial). Meets criteria but data not available. No wash‐out in between treatment periods. 1st 4 weeks' data useful but not available. Xipamide 20 mg, 40 mg or placebo |
| Webster 1980 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Weinberger 1983 | Randomized, placebo‐controlled trial (Study B). Blinding of trial not mentioned nor referenced as blinded in PubMed (MeSH terms) |
| Wiggam 1999 | A double‐blind, cross‐over study in which data are not reported at the end of the first treatment period (parallel placebo control part of the trial) |
| Wilcox 1978 | Randomized, double‐blind, placebo‐controlled trial (cross‐over trial). Does not meet inclusion criteria as treatment below the minimum 3 weeks' duration. Bendrofluazide 5 mg or 10 mg versus placebo. Each dose given for only 2 weeks |
| Wing 1982 | Meets criteria but data not available. Randomized, double‐blind, placebo‐controlled trial, cross‐over study with no wash‐out period in between treatment. 1st 5 weeks' data valid but not available |
| Wing 1997 | Randomized, double‐blind, placebo‐controlled trial (cross‐over trial). No wash‐out period before crossing over treatment. After 1st 2 weeks of double‐blind treatment HCTZ 25 mg titrated to achieve SBP < or = 160 mmHg in non‐responders only |
| Wing 1998 | Randomized, double‐blind trial (cross‐over trial). Not placebo‐controlled. No wash‐out between treatment periods. Last 2 weeks of data provided for each 6‐week phase of treatment. No thiazide monotherapy arm; combination therapy of indapamide plus perindopril only |
| Zachariah 1993 Study #1 | This double‐blind placebo‐controlled RCT meets the inclusion criteria but since the number of patients randomized to each treatment group has not been reported it had to be excluded in the data analysis |
| Zachariah 1993 Study #2 | This double‐blind placebo‐controlled RCT meets the inclusion criteria but since the number of patients randomized to each treatment group has not been reported it had to be excluded in the data analysis |
BP: blood pressure CTD: chlorthalidone d: day DBP: diastolic blood pressure ECG: electrocardiogram HCTZ: hydrochlorothiazide RCT: randomized controlled trial SBP: systolic blood pressure WDAE: withdrawals due to adverse effects