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Phase 3 Completed N=17,651 Randomized Treatment

Diuretic Comparison Project

Source: ClinicalTrials.gov NCT02185417 ↗
Enrolled (actual)
17,651
Serious AEs
29.3%
Results posted
May 2024
Primary outcomePrimary: Time From Randomization to Composite Primary Outcome — 1.5; 1.5 Years — p=0.45
◆ Published Evidence
Highly cited
149citations · ~37 / year
Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.
The New England journal of medicine · 2022 · Open access · High-confidence link

Summary

The Diuretic Comparison Project aimed to evaluate whether chlorthalidone, as compared with hydrochlorothiazide, would reduce the risk of major nonfatal cardiovascular disease outcomes and non-cancer-related deaths in older patients with hypertension who were receiving hydrochlorothiazide at baseline. The investigators incorporated the pragmatic methods used by the Department of Veterans Affairs (VA) Healthcare System to provide a real-world assessment of the effectiveness of chlorthalidone as compared with hydrochlorothiazide in routine clinical care.

Linked Publications (5)

  • Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events.
    The New England journal of medicine · 2022 · 149 citations · Open access · High-confidence link
  • A Centralized EHR-Based Model for the Recruitment of Rural and Lower Socioeconomic Participants in Pragmatic Trials: A Secondary Analysis of the Diuretic Comparison Project.
    JAMA network open · 2023 · 6 citations · Open access · High-confidence link
  • Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial.
    JAMA network open · 2024 · 4 citations · Open access · Likely link
  • Per-Protocol Analysis of Chlorthalidone Versus Hydrochlorothiazide for Cardiovascular Event Prevention-Diuretic Comparison Project.
    Journal of the American Heart Association · 2026 · 0 citations · Open access · Likely link
  • Provider experiences with and attitudes about an embedded pragmatic clinical trial.
    BMC primary care · 2025 · 0 citations · Open access · Likely link

Outcome Measures

OutcomeResultp-value
PRIMARY
Time From Randomization to Composite Primary Outcome
1.5; 1.5 0.45
PRIMARY
Proportion of Participants Had a Composite Primary Outcome
675; 702
SECONDARY
Proportion of Participants Had Nonfatal Myocardial Infarction
140; 142
SECONDARY
Proportion of Participants Had Nonfatal Stroke
83; 83
SECONDARY
Proportion of Participants Had Hospitalization for Heart Failure
232; 242
SECONDARY
Proportion of Participants Had Unstable Angina Leading to Urgent Coronary Revascularization
13; 20
SECONDARY
Proportion of Participants Deceased and Not Related to Cancer
354; 359

Eligibility Criteria

Inclusion criteria

  • over age 65 years
  • receiving hydrochlorothiazide from the VA pharmacy at a daily dose of 25 or 50 mg
  • most recent SBP ≥120 mm Hg and no records of SBP <120 mm Hg in the past 90 days

Exclusion criteria

  • impaired decision-making capacity rendering the patient unable to provide informed consent (i.e., if there is any question during the nurse's EHR chart review that the individual does not have the ability to make an autonomous decision or the PCP declines permission to randomize)
  • death expected within 6 months (inferred by PCP permission to randomize)
  • blood potassium level <3.1 or 3.5 (if taking digoxin) meq/L in the past 90 days
  • blood sodium level <130 meq/L in the past 90 days
  • enrolled in Medicare Part C (This exclusion only applied if there might be insufficient EHR data available to the study team)
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT02185417) and the linked publication. Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.

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