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Diuretics In the Management of Essential Hypertension (DIME) Study

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
University of the Ryukyus
Information provided by (Responsible Party):
Takeshi Morimoto, Kyoto University
ClinicalTrials.gov Identifier:
NCT00131846
First received: August 17, 2005
Last updated: August 22, 2012
Last verified: August 2012
History of Changes
  Purpose

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 Intervention Phase
Hypertension
 Drug: Thiazide diuretics
Drug: No diuretics
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Effect of Low Dose Thiazide Diuretics on New Onset Type 2 Diabetes in Patients With Essential Hypertension

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Kyoto University:

Primary Outcome Measures:
  • New onset type 2 diabetes (WHO criteria 1998) [ Time Frame: five years ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Treatment resistant hypokalemia less than 3.5mEq/L [ Time Frame: five years ] [ Designated as safety issue: Yes ]
  • Ischemic and hemorrhagic Strokes excluding transient ischemic attacks and secondary causes [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Myocardial infarction [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Hospitalization due to heart failure [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Arteriosclerosis obliterans (ASO) [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Total death [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Blood pressure [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Lipid profile [ Time Frame: five years ] [ Designated as safety issue: No ]
  • HbA1c [ Time Frame: five years ] [ Designated as safety issue: Yes ]
  • Fasting blood sugar [ Time Frame: five years ] [ Designated as safety issue: Yes ]
  • Direct Cost [ Time Frame: five years ] [ Designated as safety issue: No ]
  • Gout (American College of Rheumatology 1997 criteria C) [ Time Frame: five years ] [ Designated as safety issue: Yes ]

Enrollment: 1130
Study Start Date: January 2004
Estimated Study Completion Date: December 2012
Estimated Primary Completion Date: December 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   30 Years to 79 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00131846

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

No publications provided

Responsible Party: Takeshi Morimoto, Professor of Medicine, Kyoto University
ClinicalTrials.gov Identifier: NCT00131846     History of Changes
Other Study ID Numbers: H15-choju-003
Study First Received: August 17, 2005
Last Updated: August 22, 2012
Health Authority: Japan: Ministry of Health, Labor and Welfare

Keywords provided by Kyoto University:
Thiazide diuretics
Essential hypertension
Type 2 diabetes
Randomized clinical trial
Cost-effectiveness

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

ClinicalTrials.gov processed this record on May 21, 2013