Diuretic Comparison Project

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.

Timeline

Start

2016-06-15

Primary completion

2022-10-15

Completion

2022-12-29

Publications

• Background Ishani A, Leatherman SM, Woods P, Hau C, Klint A, Lew RA, Taylor AA, Glassman PA, Brophy MT, Fiore LD, Ferguson RE, Cushman WC. Design of a pragmatic clinical trial embedded in the Electronic Health Record: The VA's Diuretic Comparison Project. Contemp Clin Trials. 2022 May;116:106754. doi: 10.1016/j.cct.2022.106754. Epub 2022 Apr 4.
• Background Ferguson RE, Leatherman SM, Woods P, Hau C, Lew R, Cushman WC, Brophy MT, Fiore L, Ishani A. Practical issues in pragmatic trials: the implementation of the Diuretic Comparison Project. Clin Trials. 2023 Jun;20(3):276-283. doi: 10.1177/17407745231160553. Epub 2023 Mar 29.
• Results Ishani A, Cushman WC, Leatherman SM, Lew RA, Woods P, Glassman PA, Taylor AA, Hau C, Klint A, Huang GD, Brophy MT, Fiore LD, Ferguson RE; Diuretic Comparison Project Writing Group. Chlorthalidone vs. Hydrochlorothiazide for Hypertension-Cardiovascular Events. N Engl J Med. 2022 Dec 29;387(26):2401-2410. doi: 10.1056/NEJMoa2212270. Epub 2022 Dec 14.
• Results Hau C, Efird JT, Leatherman SM, Soloviev OV, Glassman PA, Woods PA, Ishani A, Cushman WC, Ferguson RE. 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 Netw Open. 2023 Sep 5;6(9):e2332049. doi: 10.1001/jamanetworkopen.2023.32049.
• Anand ST, Hau C, Davenport MJ, Ishani A, Cushman WC, Glassman PA, Taylor AA, Lew RA, Ferguson RE, Leatherman SM. Per-Protocol Analysis of Chlorthalidone Versus Hydrochlorothiazide for Cardiovascular Event Prevention-Diuretic Comparison Project. J Am Heart Assoc. 2026 Feb 3;15(3):e046142. doi: 10.1161/JAHA.125.046142. Epub 2026 Jan 30.
• Leatherman SM, Beaudette-Zlatanova B, Robben G, Glassman PA, Woods P, Ferguson RE, Cushman WC, Ishani A. Provider experiences with and attitudes about an embedded pragmatic clinical trial. BMC Prim Care. 2025 Apr 23;26(1):121. doi: 10.1186/s12875-025-02799-w.
• Ishani A, Hau C, Raju S, Wise JK, Glassman PA, Taylor AA, Ferguson RE, Cushman WC, Leatherman SM. Chlorthalidone vs Hydrochlorothiazide and Kidney Outcomes in Patients With Hypertension: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 Dec 2;7(12):e2449576. doi: 10.1001/jamanetworkopen.2024.49576.
• Ishani A, Hau C, Cushman WC, Leatherman SM, Lew RA, Glassman PA, Taylor AA, Ferguson RE. Chlorthalidone vs Hydrochlorothiazide for Hypertension Treatment After Myocardial Infarction or Stroke: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e2411081. doi: 10.1001/jamanetworkopen.2024.11081.
• Klint AL, Leatherman SM, Taylor O, Glassman PA, Ferguson RE, Cushman WC, Ishani A. Telephone informed consent in a pragmatic point-of-care clinical trial embedded in primary care. Contemp Clin Trials. 2023 Aug;131:107239. doi: 10.1016/j.cct.2023.107239. Epub 2023 May 25.
• Raju S, Hau C, Woods P, Flynn M, Sadatis C, McPherson J, Tella A, Ishani A, Ferguson RE, Leatherman SM. Ascertainment of stroke from administrative data to support a pragmatic embedded clinical trial. Contemp Clin Trials. 2023 Jul;130:107214. doi: 10.1016/j.cct.2023.107214. Epub 2023 May 1.
• Leatherman SM, Hau C, Klint A, Glassman PA, Taylor AA, Ferguson RE, Cushman WC, Ishani A. The impact of COVID-19 on a large pragmatic clinical trial embedded in primary care. Contemp Clin Trials. 2023 Jun;129:107179. doi: 10.1016/j.cct.2023.107179. Epub 2023 Apr 7.

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Indications