Diuretics In the Management of Essential Hypertension (DIME) Study

Study Overview
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Brief Summary
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The purpose of DIME is to evaluate the safety (i.e. new onset of diabetes and other metabolic adverse events), efficacy and cost-effectiveness of antihypertensive treatment with low dose diuretics. The researchers' hypothesis is that use of low dose thiazide diuretics is metabolically safe when used with other appropriate antihypertensives, effective in reduction of blood pressure and cheaper than treatment without diuretics. Therefore, this study is an equivalence trial.

Detailed Description
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There has been substantial evidence from clinical trials to support the rationale of use of thiazide diuretics in patients with essential hypertension. Diuretics may be more effective in reduction of blood pressure in Japanese patients than Caucasian because of higher salt intake. Moreover, given a large number of hypertensive population here, diuretics may be the most cost-effective antihypertensive agent. Japanese physicians, however, tend to avoid diuretics even in elderly hypertensive patients because of much concern over metabolic adverse events including new onset diabetes, which is deemed to increase cardiovascular risk. Although it is unlikely that use of low dose (12.5 mg of HCTZ or less) diuretics is associated with metabolic adverse events when they are given with any other appropriate antihypertensive agents (e.g. Ca antagonist, ACE inhibitor, ARB, K sparing diuretics) other than β-blockers, the researchers have to confirm the safety of low dose diuretics in terms of new onset diabetes in Japanese, who are assumed to be diabetes prone based upon thrifty gene hypothesis.

Official Title
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Effect of Low Dose Thiazide Diuretics on New Onset Type 2 Diabetes in Patients With Essential Hypertension

Conditions
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Hypertension

Intervention / Treatment
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* Drug: Thiazide diuretics
* Drug: No diuretics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 30 to 79 years With blood pressure being >150/>90 if they are not on any antihypertensive treatment With blood pressure being >140/>90 if they are already on antihypertensive drugs No history of type 2 diabetes No history of gout Exclusion Criteria: With supine blood pressure being >200/>120 Patients already on antihypertensive treatment if duration of treatment and drugs used are not identified Patients already on thiazide diuretics With type 2 diabetes With gout or hyperuricaemia (>8.0 mg/dl) With hypokalemia（<3.5mmol/L） With erectile dysfunction With renal dysfunction (s-creatinine > 2.0 mg/dL) With history of serious adverse reaction to thiazide diuretics With history of stroke or myocardial infarction within 6 months With history of percutaneous coronary intervention (PCI) or coronary artery bypass graft (CABG) within 6 months or in whom these interventions are planned With heart failure or left ventricular dysfunction (ejection fraction<40%) Patients who should be on thiazide diuretics With history of malignant tumor within 5 years Pregnant, possibility of pregnancy, or during breast feeding Patients who are deemed not eligible for this study for any reason

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Diuretics use | Drug: Thiazide diuretics<br>* Any dosage, frequency, and duration<br>|
| Active Comparator: 2<br>No diuretics use | Drug: No diuretics<br>* Any antihypertensive regimen other than diuretics<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| New onset type 2 diabetes (WHO criteria 1998) |  | five years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment resistant hypokalemia less than 3.5mEq/L |  | five years | 
| Ischemic and hemorrhagic Strokes excluding transient ischemic attacks and secondary causes |  | five years | 
| Myocardial infarction |  | five years | 
| Hospitalization due to heart failure |  | five years | 
| Arteriosclerosis obliterans (ASO) |  | five years | 
| Total death |  | five years | 
| Blood pressure |  | five years | 
| Lipid profile |  | five years | 
| HbA1c |  | five years | 
| Fasting blood sugar |  | five years | 
| Direct Cost |  | five years | 
| Gout (American College of Rheumatology 1997 criteria C) |  | five years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Thiazide diuretics, Essential hypertension, Type 2 diabetes, Randomized clinical trial, Cost-effectiveness