NCT Number: NCT02185417
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.
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Notify Me65 year and older
All sexes
Interventional
Phase 3
VA Caribbean Healthcare System, San Juan, PR, San Juan, Puerto Rico
Thiazide-type diuretics have been in use for more than 50 years and are considered as the first-line treatment for hypertension. Of the more than 1 million Veterans prescribed a thiazide-type diuretic each year, more than 95% receive hydrochlorothiazide, and fewer than 2.5% receive chlorthalidone. However, indirect evidence has been accumulating for many years that chlorthalidone may be more effective than hydrochlorothiazide at preventing cardiovascular events.
The Diuretic Comparison Project was conducted with a clinically integrated design (termed a "point of care" or "pragmatic embedded" trial). The key feature of our design was that, instead of employing local investigators, the investigators developed centralized trial procedures and implemented into the VA electronic health record (EHR) and healthcare delivery systems. This approach enabled us to conduct trial-related interactions and randomization with the use of data in the EHRs, centralize recruitment efforts without the use of site staff, eliminate the need for trial-related visits and procedures, and centralize data capture from administrative databases.
This study was performed to answer a question of whether chlorthalidone is more effective than hydrochlorothiazide at preventing cardiovascular outcomes. Consent was obtained from eligible participants who were willing to participate and their primary care providers. With provider assented to the patient undergoing randomization, 3,523 older patients with hypertension were randomized across 72 VA health care systems. Patients across the US (including Puerto Rico and District of Columbia) were enrolled. Participants were randomly assigned to continue with existing hydrochlorothiazide treatment regimen (25/50mg daily) or switch to a dose equivalent chlorthalidone (12.5/25 mg daily).
The primary outcome was the first occurrence of a composite outcome consisting of a nonfatal cardiovascular event or non-cancer related death. Nonfatal cardiovascular events included nonfatal myocardial infarction, stroke, hospitalization for heart failure, or urgent coronary revascularization for unstable angina.
Healthy volunteers accepted: No
Only the study team can determine whether someone qualifies for participation.
Inclusion criteria
Exclusion criteria
Trial activities following study randomization were considered as usual care. Prescriptions of the allocated drug were managed by the primary care providers and patients would receive the prescribed mediations through the VA outpatient pharmacy services.
Other names: HCTZ
Trial activities following study randomization were considered as usual care. Prescriptions of the allocated drug were managed by the primary care providers and patients would receive the prescribed mediations through the VA outpatient pharmacy services.
Other names: CTD
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Time to study primary outcome was defined as years from randomization to the first occurrence of a composite endpoint, consisting of a nonfatal cardiovascular event or non-cancer related death. Nonfatal cardiovascular events included nonfatal myocardial infarction, stroke, hospitalization for heart failure, or urgent coronary revascularization for unstable angina. For participants who had a primary outcome, time to event was determined as the earliest admission or death date. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
The primary outcome was the first occurrence of a composite endpoint consisting of a nonfatal cardiovascular event or non-cancer related death. Nonfatal cardiovascular events included nonfatal myocardial infarction, stroke, hospitalization for heart failure, or urgent coronary revascularization for unstable angina. Time to the first event was computed based on the earliest hospital admission or death dates. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Secondary outcomes were the individual components of the primary outcome. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Secondary outcomes were the individual components of the primary outcome. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Secondary outcomes were the individual components of the primary outcome. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Collection of outcome data were performed from randomization until participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Secondary outcomes were the individual components of the primary outcome. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
Time frame: Outcome data collection was performed from study randomization until the participants deceased, withdrawn, or reached end of study (Up to 5.4 years for the first patient enrolled and an average of 2.4 years for all participants).
Secondary outcomes were the individual components of the primary outcome. Ascertainment of study outcomes was made with the use of administrative and clinical data obtained from VA EHRs through June 1, 2022, from records of Medicare claims obtained from the Centers for Medicare and Medicaid Services through 2021, and from National Death Index records through 2019. Trial outcomes were ascertained with the use of validated EHR phenotypes and, when needed, manual adjudication. Manually adjudicated outcomes were evaluated by investigators and staff who were unaware of group assignment.
VA Office of Research and Development
Fed
CSP #597 - Diuretic Comparison Project
Acronym: DCP
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