Clinical trial NCT00131846: Diuretics In the Management of Essential Hypertension (DIME) Study
Official title: Effect of Low Dose Thiazide Diuretics on New Onset Type 2 Diabetes in Patients With Essential Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Hypertension
Keywords: Thiazide diuretics
Essential hypertension
Type 2 diabetes
Randomized clinical trial
Cost-effectiveness
Lead sponsor: Kyoto University
Sponsor class: OTHER
Collaborators: name: University of the Ryukyus
First posted: 2005-08-19
Enrollment: 1130
Sex: ALL
Minimum age (years): 30
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: New onset type 2 diabetes (WHO criteria 1998)
timeFrame: five years
Secondary outcomes:
measure: Treatment resistant hypokalemia less than 3.5mEq/L
timeFrame: five years
measure: Ischemic and hemorrhagic Strokes excluding transient ischemic attacks and secondary causes
timeFrame: five years
measure: Myocardial infarction
timeFrame: five years
measure: Hospitalization due to heart failure
timeFrame: five years
measure: Arteriosclerosis obliterans (ASO)
timeFrame: five years
measure: Total death
timeFrame: five years
measure: Blood pressure
timeFrame: five years
measure: Lipid profile
timeFrame: five years
measure: HbA1c
timeFrame: five years
measure: Fasting blood sugar
timeFrame: five years
measure: Direct Cost
timeFrame: five years
measure: Gout (American College of Rheumatology 1997 criteria C)
timeFrame: five years
Other outcomes:
Locations:
city: Nishihara-cho
country: Japan
facility: University of the Ryukyus
state: Okinawa
Study officials:
affiliation: Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus
name: Shinichiro Ueda, MB, ChB, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ueda S, Morimoto T, Ando S, Takishita S, Kawano Y, Shimamoto K, Ogihara T, Saruta T; DIME Investigators. A randomised controlled trial for the evaluation of risk for type 2 diabetes in hypertensive patients receiving thiazide diuretics: Diuretics In the Management of Essential hypertension (DIME) study. BMJ Open. 2014 Jul 16;4(7):e004576. doi: 10.1136/bmjopen-2013-004576.