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

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.

Condition or disease Intervention/treatment Phase
Hypertension Drug: Thiazide diuretics Drug: No diuretics Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 1130 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of Low Dose Thiazide Diuretics on New Onset Type 2 Diabetes in Patients With Essential Hypertension
Actual Study Start Date : April 2004
Actual Primary Completion Date : August 2012
Actual Study Completion Date : November 2013

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Active Comparator: 1
Diuretics use
Drug: Thiazide diuretics
Any dosage, frequency, and duration

Active Comparator: 2
No diuretics use
Drug: No diuretics
Any antihypertensive regimen other than diuretics

Primary Outcome Measures :
  1. New onset type 2 diabetes (WHO criteria 1998) [ Time Frame: five years ]

Secondary Outcome Measures :
  1. Treatment resistant hypokalemia less than 3.5mEq/L [ Time Frame: five years ]
  2. Ischemic and hemorrhagic Strokes excluding transient ischemic attacks and secondary causes [ Time Frame: five years ]
  3. Myocardial infarction [ Time Frame: five years ]
  4. Hospitalization due to heart failure [ Time Frame: five years ]
  5. Arteriosclerosis obliterans (ASO) [ Time Frame: five years ]
  6. Total death [ Time Frame: five years ]
  7. Blood pressure [ Time Frame: five years ]
  8. Lipid profile [ Time Frame: five years ]
  9. HbA1c [ Time Frame: five years ]
  10. Fasting blood sugar [ Time Frame: five years ]
  11. Direct Cost [ Time Frame: five years ]
  12. Gout (American College of Rheumatology 1997 criteria C) [ Time Frame: five years ]

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Ages Eligible for Study:   30 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00131846

University of the Ryukyus
Nishihara-cho, Okinawa, Japan, 903-0215
Sponsors and Collaborators
Kyoto University
University of the Ryukyus
Principal Investigator: Shinichiro Ueda, MB, ChB, PhD Department of Clinical Pharmacology & Therapeutics, University of the Ryukyus

Publications automatically indexed to this study by Identifier (NCT Number):
Responsible Party: Takeshi Morimoto, Professor of Medicine, Kyoto University Identifier: NCT00131846     History of Changes
Other Study ID Numbers: H15-choju-003
First Posted: August 19, 2005    Key Record Dates
Last Update Posted: March 15, 2017
Last Verified: March 2017

Keywords provided by Takeshi Morimoto, Kyoto University:
Thiazide diuretics
Essential hypertension
Type 2 diabetes
Randomized clinical trial

Additional relevant MeSH terms:
Vascular Diseases
Cardiovascular Diseases
Sodium Chloride Symporter Inhibitors
Natriuretic Agents
Physiological Effects of Drugs
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action