Diuretics In the Management of Essential Hypertension (DIME) Study

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00131846
Recruitment Status : Completed
First Posted : August 19, 2005
Last Update Posted : March 15, 2017
University of the Ryukyus
Information provided by (Responsible Party):
Takeshi Morimoto, Kyoto University

August 17, 2005
August 19, 2005
March 15, 2017
April 2004
August 2012   (Final data collection date for primary outcome measure)
New onset type 2 diabetes (WHO criteria 1998) [ Time Frame: five years ]
New onset type 2 diabetes
Complete list of historical versions of study NCT00131846 on Archive Site
  • Treatment resistant hypokalemia less than 3.5mEq/L [ Time Frame: five years ]
  • Ischemic and hemorrhagic Strokes excluding transient ischemic attacks and secondary causes [ Time Frame: five years ]
  • Myocardial infarction [ Time Frame: five years ]
  • Hospitalization due to heart failure [ Time Frame: five years ]
  • Arteriosclerosis obliterans (ASO) [ Time Frame: five years ]
  • Total death [ Time Frame: five years ]
  • Blood pressure [ Time Frame: five years ]
  • Lipid profile [ Time Frame: five years ]
  • HbA1c [ Time Frame: five years ]
  • Fasting blood sugar [ Time Frame: five years ]
  • Direct Cost [ Time Frame: five years ]
  • Gout (American College of Rheumatology 1997 criteria C) [ Time Frame: five years ]
  • Gout
  • Treatment resistant hypokalemia
  • Stroke
  • Myocardial infarction
  • Hospitalization due to heart failure
  • ASO
  • Total death
  • Blood pressure
  • Lipid profile
  • HbA1c
  • Fasting blood sugar
  • Cost
Not Provided
Not Provided
Diuretics In the Management of Essential Hypertension (DIME) Study
Effect of Low Dose Thiazide Diuretics on New Onset Type 2 Diabetes in Patients With Essential Hypertension
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.
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.
Phase 4
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
  • Drug: Thiazide diuretics
    Any dosage, frequency, and duration
  • Drug: No diuretics
    Any antihypertensive regimen other than diuretics
  • Active Comparator: 1
    Diuretics use
    Intervention: Drug: Thiazide diuretics
  • Active Comparator: 2
    No diuretics use
    Intervention: Drug: No diuretics
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.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
November 2013
August 2012   (Final data collection date for primary outcome measure)

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
Sexes Eligible for Study: All
30 Years to 79 Years   (Adult, Older Adult)
Contact information is only displayed when the study is recruiting subjects
Not Provided
Not Provided
Takeshi Morimoto, Kyoto University
Kyoto University
University of the Ryukyus
Principal Investigator: Shinichiro Ueda, MB, ChB, PhD Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus
Kyoto University
March 2017

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