<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT02185417</url>
  </required_header>
  <id_info>
    <org_study_id>597</org_study_id>
    <nct_id>NCT02185417</nct_id>
  </id_info>
  <brief_title>Diuretic Comparison Project</brief_title>
  <acronym>DCP</acronym>
  <official_title>CSP #597 - Diuretic Comparison Project</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to determine whether chlorthalidone is more effective than&#xD;
      hydrochlorothiazide at preventing cardiovascular outcomes in Veterans over age 65 with&#xD;
      hypertension. Both medications are thiazide-type diuretics that have been used for more than&#xD;
      50 years and are considered first-line treatment for hypertension. Patients currently&#xD;
      prescribed hydrochlorothiazide will be randomized to either continue taking&#xD;
      hydrochlorothiazide or to receive chlorthalidone, and followed for major cardiovascular&#xD;
      events, such as myocardial infarction (MI) and stroke. The study will use a new, efficient&#xD;
      and less expensive study design termed 'point of care', in which study operations will be&#xD;
      conducted centrally and patient data will be collected passively through the electronic&#xD;
      medical record.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Over 1 million Veterans are prescribed a thiazide-type diuretic each year; over 95% receive&#xD;
      hydrochlorothiazide, and fewer than 2.5% receive chlorthalidone. Both medications are&#xD;
      thiazide-type diuretics that have been used for more than 50 years and are considered&#xD;
      first-line treatment for hypertension. Indirect evidence has been accumulating, however, that&#xD;
      chlorthalidone may be more effective than hydrochlorothiazide at preventing cardiovascular&#xD;
      events. This will be the first randomized head-to-head comparison of the effectiveness of&#xD;
      these two drugs. The study plans to enroll 13,500 Veterans over 3 years and follow them on&#xD;
      average for 3 years, resulting in a total study duration of 4.5 years. Patients currently&#xD;
      prescribed hydrochlorothiazide will be randomized to either continue taking&#xD;
      hydrochlorothiazide or to receive an equivalent dose of chlorthalidone. The unique 'point of&#xD;
      care' or 'clinically integrated' study design will identify, enroll and follow subjects using&#xD;
      the electronic medical record system and national VA and non-VA databases. The primary&#xD;
      outcome is an event composite consisting of: stroke, myocardial infarction, non-cancer death,&#xD;
      urgent revascularization, and hospitalization for acute congestive heart failure. All patient&#xD;
      care, including the study drug, will continue to be managed by the primary care provider.&#xD;
&#xD;
      Primary Care Providers will also be included as participants in this research study. Adding&#xD;
      providers as subjects will allow us to study the implementation of the point of care protocol&#xD;
      design in addition to the original research question. The study team will collect data on&#xD;
      diuretic management within the study and may contact providers by phone or email to learn&#xD;
      reasons for declining a particular patient or discontinuing a new chlorthalidone order or an&#xD;
      ongoing diuretic prescription.&#xD;
&#xD;
      If cardiovascular events are reduced by even a small amount by chlorthalidone, the public&#xD;
      health effect will be considerable because of the large number of patients who take&#xD;
      diuretics. A randomized trial, now feasible due to the investigators' efficient and&#xD;
      inexpensive design, will provide evidence needed to better inform practice throughout the VA.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 15, 2016</start_date>
  <completion_date type="Actual">December 29, 2022</completion_date>
  <primary_completion_date type="Actual">October 15, 2022</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Time to major cardiovascular event</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to event for each component of the composite primary outcome and additional cardiovascular events</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>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) &quot;possibly vascular deaths,&quot; (5) the composite outcome substituting &quot;possibly vascular deaths&quot; for non-cancer deaths, (6) any revascularization of any artery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>All Deaths</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>All Deaths</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The primary composite outcome substituting 'all deaths' for 'non-cancer deaths'</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Possibly Vascular Deaths</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>Defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The primary composite outcome substituting 'possibly vascular deaths' for 'non-cancer deaths'</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Any revascularization of any artery</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>Any revascularization of any artery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Erectile dysfunction (ED)</measure>
    <time_frame>Randomization to time to event; average follow-up 3 years</time_frame>
    <description>Defined as first prescription for phosphodiesterase Type 5 (PDE5) inhibitor or referral for ED</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">13523</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Hydrochlorothiazide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Hydrochlorothiazide daily dose of 50 mg or 25 mg for duration of study</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Chlorthalidone</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Chlorthalidone daily dose of 25 mg or 12.5 mg for duration of study</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Hydrochlorothiazide (HCTZ)</intervention_name>
    <description>Thiazide-type diuretic. Daily dose of 50 or 25 mg for duration of the study.</description>
    <arm_group_label>Hydrochlorothiazide</arm_group_label>
    <other_name>HCTZ</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Chlorthalidone</intervention_name>
    <description>Thiazide-type diuretic. Daily dose of 25 or 12.5 mg for duration of the study.</description>
    <arm_group_label>Chlorthalidone</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Veterans who:&#xD;
&#xD;
          -  Are over age 65 years&#xD;
&#xD;
          -  Are receiving hydrochlorothiazide from the VA pharmacy at a daily dose of 25 or 50 mg&#xD;
&#xD;
          -  Have a most recent systolic blood pressure (SBP) in CPRS greater than or equal to 120&#xD;
             mm Hg, with no SBP less than 120 mm Hg recorded in CPRS in the previous 90 days&#xD;
&#xD;
        Primary Care Providers will also be included as participants in this research study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Impaired decision-making capacity rendering the patient unable to provide informed&#xD;
             consent (i.e., if there is any question during the nurse's EMR chart review that the&#xD;
             individual does not have the ability to make an autonomous decision or the PCP&#xD;
             declines permission to randomize)&#xD;
&#xD;
          -  Death expected within 6 months (inferred by PCP permission to randomize)&#xD;
&#xD;
          -  K&lt;3.1 meq/L (or K&lt;3.5 meq/L if on digoxin) in the past 90 days&#xD;
&#xD;
          -  Na&lt;130 meq/L in the past 90 days&#xD;
&#xD;
          -  Known to be enrolled in Medicare Part C (assessed on consent phone call). This&#xD;
             exclusion will only be employed if the investigators determine that sufficient&#xD;
             information from Part C data cannot obtained.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>65 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Areef Ishani, MD MS</last_name>
    <role>Study Chair</role>
    <affiliation>Minneapolis VA Health Care System, Minneapolis, MN</affiliation>
  </overall_official>
  <overall_official>
    <last_name>William C Cushman, MD</last_name>
    <role>Study Chair</role>
    <affiliation>Memphis VA Medical Center, Memphis, TN</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Birmingham VA Medical Center, Birmingham, AL</name>
      <address>
        <city>Birmingham</city>
        <state>Alabama</state>
        <zip>35233</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Alaska VA Healthcare System, Anchorage, AK</name>
      <address>
        <city>Anchorage</city>
        <state>Alaska</state>
        <zip>99504</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Veterans Health Care System of the Ozarks, Fayetteville, AR</name>
      <address>
        <city>Fayetteville</city>
        <state>Arkansas</state>
        <zip>72703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Central Arkansas VHS John L. McClellan Memorial Veterans Hospital, Little Rock, AR</name>
      <address>
        <city>Little Rock</city>
        <state>Arkansas</state>
        <zip>72205-5484</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Central California Health Care System, Fresno, CA</name>
      <address>
        <city>Fresno</city>
        <state>California</state>
        <zip>93703</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Long Beach Healthcare System, Long Beach, CA</name>
      <address>
        <city>Long Beach</city>
        <state>California</state>
        <zip>90822</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Palo Alto Health Care System, Palo Alto, CA</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304-1290</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Greater Los Angeles Healthcare System, West Los Angeles, CA</name>
      <address>
        <city>West Los Angeles</city>
        <state>California</state>
        <zip>90073</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rocky Mountain Regional VA Medical Center, Aurora, CO</name>
      <address>
        <city>Aurora</city>
        <state>Colorado</state>
        <zip>80045</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Grand Junction VA Medical Center, Grand Junction, CO</name>
      <address>
        <city>Grand Junction</city>
        <state>Colorado</state>
        <zip>81501</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Connecticut Healthcare System West Haven Campus, West Haven, CT</name>
      <address>
        <city>West Haven</city>
        <state>Connecticut</state>
        <zip>06516</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilmington VA Medical Center, Wilmington, DE</name>
      <address>
        <city>Wilmington</city>
        <state>Delaware</state>
        <zip>19805</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Washington DC VA Medical Center, Washington, DC</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20422</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Bay Pines VA Healthcare System, Pay Pines, FL</name>
      <address>
        <city>Bay Pines</city>
        <state>Florida</state>
        <zip>33744</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>North Florida/South Georgia Veterans Health System, Gainesville, FL</name>
      <address>
        <city>Gainesville</city>
        <state>Florida</state>
        <zip>32608</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Pacific Islands Health Care System, Honolulu, HI</name>
      <address>
        <city>Honolulu</city>
        <state>Hawaii</state>
        <zip>96819-1522</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Boise VA Medical Center, Boise, ID</name>
      <address>
        <city>Boise</city>
        <state>Idaho</state>
        <zip>83702</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Illiana Health Care System, Danville, IL</name>
      <address>
        <city>Danville</city>
        <state>Illinois</state>
        <zip>61832</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edward Hines Jr. VA Hospital, Hines, IL</name>
      <address>
        <city>Hines</city>
        <state>Illinois</state>
        <zip>60141-5000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Captain James A. Lovell Federal Health Care Center, North Chicago, IL</name>
      <address>
        <city>North Chicago</city>
        <state>Illinois</state>
        <zip>60064</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Richard L. Roudebush VA Medical Center, Indianapolis, IN</name>
      <address>
        <city>Indianapolis</city>
        <state>Indiana</state>
        <zip>46202-2884</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Central Iowa Health Care System, Des Moines, IA</name>
      <address>
        <city>Des Moines</city>
        <state>Iowa</state>
        <zip>50310-5774</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Iowa City VA Health Care System, Iowa City, IA</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52246-2208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Maine VA Medical Center, Augusta, ME</name>
      <address>
        <city>Togus</city>
        <state>Maine</state>
        <zip>04330</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rehabilitation R&amp;D Service, Baltimore, MD</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Edith Nourse Rogers Memorial Veterans Hospital, Bedford, MA</name>
      <address>
        <city>Bedford</city>
        <state>Massachusetts</state>
        <zip>01730</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Boston Healthcare System Jamaica Plain Campus, Jamaica Plain, MA</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02130</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Aleda E. Lutz VA Medical Center, Saginaw, MI</name>
      <address>
        <city>Saginaw</city>
        <state>Michigan</state>
        <zip>48602</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis VA Health Care System, Minneapolis, MN</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55417-2309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Minneapolis VA Health Care System, Minneapolis, MN</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55417</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Cloud VA Health Care System, St. Cloud, MN</name>
      <address>
        <city>Saint Cloud</city>
        <state>Minnesota</state>
        <zip>56303</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Gulf Coast Veterans Health Care System, Biloxi, MS</name>
      <address>
        <city>Biloxi</city>
        <state>Mississippi</state>
        <zip>39531</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kansas City VA Medical Center, Kansas City, MO</name>
      <address>
        <city>Kansas City</city>
        <state>Missouri</state>
        <zip>64128</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>St. Louis VA Medical Center John Cochran Division, St. Louis, MO</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Omaha VA Nebraska-Western Iowa Health Care System, Omaha, NE</name>
      <address>
        <city>Omaha</city>
        <state>Nebraska</state>
        <zip>68105-1873</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manchester VA Medical Center, Manchester, NH</name>
      <address>
        <city>Manchester</city>
        <state>New Hampshire</state>
        <zip>03104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New Mexico VA Health Care System, Albuquerque, NM</name>
      <address>
        <city>Albuquerque</city>
        <state>New Mexico</state>
        <zip>87108-5153</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Albany VA Medical Center Samuel S. Stratton, Albany, NY</name>
      <address>
        <city>Albany</city>
        <state>New York</state>
        <zip>12208</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Manhattan Campus of the VA NY Harbor Healthcare System, New York, NY</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10010</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Syracuse VA Medical Center, Syracuse, NY</name>
      <address>
        <city>Syracuse</city>
        <state>New York</state>
        <zip>13210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Durham VA Medical Center, Durham, NC</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Fargo VA Healthcare System, Fargo, ND</name>
      <address>
        <city>Fargo</city>
        <state>North Dakota</state>
        <zip>58102</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Cincinnati VA Medical Center, Cincinnati, OH</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45220</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Louis Stokes VA Medical Center, Cleveland, OH</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44106</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Dayton VA Medical Center, Dayton, OH</name>
      <address>
        <city>Dayton</city>
        <state>Ohio</state>
        <zip>45428</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Jackson C. Montgomery VA Medical Center, Muskogee, OK</name>
      <address>
        <city>Muskogee</city>
        <state>Oklahoma</state>
        <zip>74401</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Portland Health Care System, Portland, OR</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Roseburg Healthcare System, Roseburg, OR</name>
      <address>
        <city>Roseburg</city>
        <state>Oregon</state>
        <zip>97471</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Southern Oregon Rehabilitation Center and Clinics, White City, OR</name>
      <address>
        <city>White City</city>
        <state>Oregon</state>
        <zip>97503</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Coatesville VA Medical Center, Coatesville, PA</name>
      <address>
        <city>Coatesville</city>
        <state>Pennsylvania</state>
        <zip>19320</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Pittsburgh Healthcare System University Drive Division, Pittsburgh, PA</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15240</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wilkes-Barre VA Medical Center, Wilkes-Barre, PA</name>
      <address>
        <city>Wilkes-Barre</city>
        <state>Pennsylvania</state>
        <zip>18711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ralph H. Johnson VA Medical Center, Charleston, SC</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29401-5799</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Wm. Jennings Bryan Dorn VA Medical Center, Columbia, SC</name>
      <address>
        <city>Columbia</city>
        <state>South Carolina</state>
        <zip>29209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Black Hills Health Care System Fort Meade Campus, Fort Meade, SD</name>
      <address>
        <city>Fort Meade</city>
        <state>South Dakota</state>
        <zip>57741</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis VA Medical Center, Memphis, TN</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104-2127</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Memphis VA Medical Center, Memphis, TN</name>
      <address>
        <city>Memphis</city>
        <state>Tennessee</state>
        <zip>38104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tennessee Valley Healthcare System Nashville Campus, Nashville, TN</name>
      <address>
        <city>Nashville</city>
        <state>Tennessee</state>
        <zip>37212-2637</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA North Texas Health Care System Dallas VA Medical Center, Dallas, TX</name>
      <address>
        <city>Dallas</city>
        <state>Texas</state>
        <zip>75216</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Michael E. DeBakey VA Medical Center, Houston, TX</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>South Texas Health Care System, San Antonio, TX</name>
      <address>
        <city>San Antonio</city>
        <state>Texas</state>
        <zip>78229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>White River Junction VA Medical Center, White River Junction, VT</name>
      <address>
        <city>White River Junction</city>
        <state>Vermont</state>
        <zip>05009-0001</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hampton VA Medical Center, Hampton, VA</name>
      <address>
        <city>Hampton</city>
        <state>Virginia</state>
        <zip>23667</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Huntington VA Medical Center, Huntington, WV</name>
      <address>
        <city>Huntington</city>
        <state>West Virginia</state>
        <zip>25704</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>William S. Middleton Memorial Veterans Hospital, Madison, WI</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Clement J. Zablocki VA Medical Center, Milwaukee, WI</name>
      <address>
        <city>Milwaukee</city>
        <state>Wisconsin</state>
        <zip>53295-1000</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tomah VA Medical Center, Tomah, WI</name>
      <address>
        <city>Tomah</city>
        <state>Wisconsin</state>
        <zip>54660</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sheridan VA Medical Center, Sheridan, WY</name>
      <address>
        <city>Sheridan</city>
        <state>Wyoming</state>
        <zip>82801</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>VA Caribbean Healthcare System, San Juan, PR</name>
      <address>
        <city>San Juan</city>
        <zip>00921</zip>
        <country>Puerto Rico</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Puerto Rico</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>35390512</PMID>
  </reference>
  <results_reference>
    <citation>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.</citation>
    <PMID>36516076</PMID>
  </results_reference>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 30, 2014</study_first_submitted>
  <study_first_submitted_qc>July 3, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 9, 2014</study_first_posted>
  <last_update_submitted>July 26, 2023</last_update_submitted>
  <last_update_submitted_qc>July 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 1, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Hypertension</keyword>
  <keyword>Diuretic</keyword>
  <keyword>Comparative Effectiveness Research</keyword>
  <keyword>Point of Care Research</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypertension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hydrochlorothiazide</mesh_term>
    <mesh_term>Chlorthalidone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>There is no IPD sharing plan description</ipd_description>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>October 26, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02185417/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>October 27, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02185417/SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 18, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT02185417/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT02185417
org study id: 597
nct id: NCT02185417
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: No
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.
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.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Time to major cardiovascular event
time frame: Randomization to time to event; average follow-up 3 years
description: 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.
measure: 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
description: 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.
measure: All Deaths
time frame: Randomization to time to event; average follow-up 3 years
description: All Deaths
measure: The primary composite outcome substituting 'all deaths' for 'non-cancer deaths'
time frame: Randomization to time to event; average follow-up 3 years
description: 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.
measure: Possibly Vascular Deaths
time frame: Randomization to time to event; average follow-up 3 years
description: Defined as all deaths caused by vascular diseases, diabetes, external causes, and unknown causes.
measure: The primary composite outcome substituting 'possibly vascular deaths' for 'non-cancer deaths'
time frame: Randomization to time to event; average follow-up 3 years
description: 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.
measure: Any revascularization of any artery
time frame: Randomization to time to event; average follow-up 3 years
description: Any revascularization of any artery
measure: Erectile dysfunction (ED)
time frame: Randomization to time to event; average follow-up 3 years
description: Defined as first prescription for phosphodiesterase Type 5 (PDE5) inhibitor or referral for ED
arm group label: Hydrochlorothiazide
arm group type: Active Comparator
description: Hydrochlorothiazide daily dose of 50 mg or 25 mg for duration of study
arm group label: Chlorthalidone
arm group type: Active Comparator
description: Chlorthalidone daily dose of 25 mg or 12.5 mg for duration of study
intervention type: Drug
intervention name: Hydrochlorothiazide (HCTZ)
description: Thiazide-type diuretic. Daily dose of 50 or 25 mg for duration of the study.
arm group label: Hydrochlorothiazide
other name: HCTZ
intervention type: Drug
intervention name: Chlorthalidone
description: Thiazide-type diuretic. Daily dose of 25 or 12.5 mg for duration of the study.
arm group label: Chlorthalidone
criteria: 
gender: All
minimum age: 65 Years
maximum age: N/A
healthy volunteers: No
last name: Areef Ishani, MD MS
role: Study Chair
affiliation: Minneapolis VA Health Care System, Minneapolis, MN
last name: William C Cushman, MD
role: Study Chair
affiliation: Memphis VA Medical Center, Memphis, TN
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country: Puerto Rico
country: United States
citation: 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.
PMID: 35390512
citation: 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.
PMID: 36516076
responsible party type: Sponsor
mesh term: Hypertension
mesh term: Hydrochlorothiazide
mesh term: Chlorthalidone
sharing ipd: No
ipd description: There is no IPD sharing plan description
provided document: 
provided document: 
provided document: 