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Diuretic Comparison Project (DCP)

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ClinicalTrials.gov Identifier: NCT02185417
Recruitment Status : Recruiting
First Posted : July 9, 2014
Last Update Posted : December 11, 2020
Sponsor:
Information provided by (Responsible Party):
VA Office of Research and Development

Tracking Information
First Submitted Date  ICMJE June 30, 2014
First Posted Date  ICMJE July 9, 2014
Last Update Posted Date December 11, 2020
Actual Study Start Date  ICMJE June 15, 2016
Estimated Primary Completion Date October 15, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 4, 2014)
Time to major cardiovascular event [ Time Frame: Randomization to time to event; average follow-up 3 years ]
The Primary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, non-cancer death.
Original Primary Outcome Measures  ICMJE
 (submitted: July 3, 2014)
Time to major cardiovasular event [ Time Frame: Randomization to time to event; average follow-up 3 years ]
The Primary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, non-cancer death.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 27, 2017)
  • Time to event for each component of the composite primary outcome and additional cardiovascular events [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    The Secondary outcomes will include time to event for (1) each of the 5 components of the composite primary outcome, (2) all deaths, (3) the composite outcome substituting all deaths for non-cancer deaths, (4) "possibly vascular deaths," (5) the composite outcome substituting "possibly vascular deaths" for non-cancer deaths, (6) any revascularization of any artery.
  • All Deaths [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    All Deaths
  • Urgent revascularization because of unstable angina [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Urgent revascularization because of unstable angina
  • Hospitalization for acute congestive heart failure [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Hospitalization for acute congestive heart failure
  • Non-cancer death [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Non-cancer death
  • The primary composite outcome substituting 'all deaths' for 'non-cancer deaths' [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    This secondary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, all deaths.
  • Possibly Vascular Deaths [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.
  • The primary composite outcome substituting 'possibly vascular deaths' for 'non-cancer deaths' [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    This secondary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, possibly vascular deaths. 'Possibly vascular deaths' are defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.
  • Any revascularization of any artery [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Any revascularization of any artery
  • Erectile dysfunction (ED) [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Defined as first prescription for phosphodiesterase Type 5 (PDE5) inhibitor or referral for ED
Original Secondary Outcome Measures  ICMJE
 (submitted: July 3, 2014)
  • Time to event for each component of the composite primary outcome and additional cardiovascular events [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    The Secondary outcomes will include time to event for (1) each of the 5 components of the composite primary outcome, (2) all deaths, (3) the composite outcome substituting all deaths for non-cancer deaths, (4) "possibly vascular deaths," (5) the composite outcome substituting "possibly vascular deaths" for non-cancer deaths, (6) any revascularization of any artery.
  • All Deaths [ Time Frame: Randomization to time to event; average follow-up 3 years ]
  • Urgent revascularization because of unstable angina [ Time Frame: Randomization to time to event; average follow-up 3 years ]
  • Hospitalization for acute congestive heart failure [ Time Frame: Randomization to time to event; average follow-up 3 years ]
  • Non-cancer death [ Time Frame: Randomization to time to event; average follow-up 3 years ]
  • The primary composite outcome substituting 'all deaths' for 'non-cancer deaths' [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    This secondary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, all deaths.
  • Possibly Vascular Deaths [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    Defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.
  • The primary composite outcome substituting 'possibly vascular deaths' for 'non-cancer deaths' [ Time Frame: Randomization to time to event; average follow-up 3 years ]
    This secondary outcome measure will be time to a major cardiovascular event, defined as a composite outcome comprised of the first occurrence after randomization of any of the following: stroke, myocardial infarction, urgent coronary revascularization because of unstable angina, hospitalization for acute congestive heart failure, possibly vascular deaths. 'Possibly vascular deaths' are defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.
  • Any revascularization of any artery [ Time Frame: Randomization to time to event; average follow-up 3 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Diuretic Comparison Project
Official Title  ICMJE CSP #597 - Diuretic Comparison Project
Brief Summary The purpose of this study is to determine whether chlorthalidone is more effective than hydrochlorothiazide at preventing cardiovascular outcomes in Veterans over age 65 with hypertension. Both medications are thiazide-type diuretics that have been used for more than 50 years and are considered first-line treatment for hypertension. Patients currently prescribed hydrochlorothiazide will be randomized to either continue taking hydrochlorothiazide or to receive chlorthalidone, and followed for major cardiovascular events, such as myocardial infarction (MI) and stroke. The study will use a new, efficient and less expensive study design termed 'point of care', in which study operations will be conducted centrally and patient data will be collected passively through the electronic medical record.
Detailed Description

Over 1 million Veterans are prescribed a thiazide-type diuretic each year; over 95% receive hydrochlorothiazide, and fewer than 2.5% receive chlorthalidone. Both medications are thiazide-type diuretics that have been used for more than 50 years and are considered first-line treatment for hypertension. Indirect evidence has been accumulating, however, that chlorthalidone may be more effective than hydrochlorothiazide at preventing cardiovascular events. This will be the first randomized head-to-head comparison of the effectiveness of these two drugs. The study plans to enroll 13,500 Veterans over 3 years and follow them on average for 3 years, resulting in a total study duration of 4.5 years. Patients currently prescribed hydrochlorothiazide will be randomized to either continue taking hydrochlorothiazide or to receive an equivalent dose of chlorthalidone. The unique 'point of care' or 'clinically integrated' study design will identify, enroll and follow subjects using the electronic medical record system and national VA and non-VA databases. The primary outcome is an event composite consisting of: stroke, myocardial infarction, non-cancer death, urgent revascularization, and hospitalization for acute congestive heart failure. All patient care, including the study drug, will continue to be managed by the primary care provider.

Primary Care Providers will also be included as participants in this research study. Adding providers as subjects will allow us to study the implementation of the point of care protocol design in addition to the original research question. The study team will collect data on diuretic management within the study and may contact providers by phone or email to learn reasons for declining a particular patient or discontinuing a new chlorthalidone order or an ongoing diuretic prescription.

If cardiovascular events are reduced by even a small amount by chlorthalidone, the public health effect will be considerable because of the large number of patients who take diuretics. A randomized trial, now feasible due to the investigators' efficient and inexpensive design, will provide evidence needed to better inform practice throughout the VA.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Hypertension
Intervention  ICMJE
  • Drug: Hydrochlorothiazide (HCTZ)
    Thiazide-type diuretic. Daily dose of 50 or 25 mg for duration of the study.
    Other Name: HCTZ
  • Drug: Chlorthalidone
    Thiazide-type diuretic. Daily dose of 25 or 12.5 mg for duration of the study.
Study Arms  ICMJE
  • Active Comparator: Hydrochlorothiazide
    Hydrochlorothiazide daily dose of 50 mg or 25 mg for duration of study
    Intervention: Drug: Hydrochlorothiazide (HCTZ)
  • Active Comparator: Chlorthalidone
    Chlorthalidone daily dose of 25 mg or 12.5 mg for duration of study
    Intervention: Drug: Chlorthalidone
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 3, 2014)
13500
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE April 15, 2023
Estimated Primary Completion Date October 15, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

Veterans who:

  • Are over age 65 years
  • Are receiving hydrochlorothiazide from the VA pharmacy at a daily dose of 25 or 50 mg
  • Have a most recent systolic blood pressure (SBP) in CPRS greater than or equal to 120 mm Hg, with no SBP less than 120 mm Hg recorded in CPRS in the previous 90 days

Primary Care Providers will also be included as participants in this research study.

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 EMR 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)
  • K<3.1 meq/L (or K<3.5 meq/L if on digoxin) in the past 90 days
  • Na<130 meq/L in the past 90 days
  • Known to be enrolled in Medicare Part C (assessed on consent phone call). This exclusion will only be employed if the investigators determine that sufficient information from Part C data cannot obtained.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 65 Years and older   (Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Alison L Majkut (857) 364-4885 Alison.Majkut@va.gov
Contact: Gregory A Robben, BA (857) 364-6120 gregory.robben@va.gov
Listed Location Countries  ICMJE Puerto Rico,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02185417
Other Study ID Numbers  ICMJE 597
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: There is no IPD sharing plan description
Responsible Party VA Office of Research and Development
Study Sponsor  ICMJE VA Office of Research and Development
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Chair: Areef Ishani, MD MS Minneapolis VA Health Care System, Minneapolis, MN
Study Chair: William C Cushman, MD Memphis VA Medical Center, Memphis, TN
PRS Account VA Office of Research and Development
Verification Date December 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP