<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/NCT04455178</url>
  </required_header>
  <id_info>
    <org_study_id>SIRRHF</org_study_id>
    <nct_id>NCT04455178</nct_id>
  </id_info>
  <brief_title>The Comparison Between Spironolactone and Indapamide Monotherapy or in Combination With Amlodipine to Reduce the Risk of Heart Failure</brief_title>
  <acronym>SIRRHF</acronym>
  <official_title>The Comparison Between Spironolactone and Indapamide Monotherapy or in Combination With Amlodipine to Reduce the Risk of Heart Failure</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Jiao Tong University School of Medicine</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Jiao Tong University School of Medicine</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      1. Study name: The comparison between spironolactone and indapamide monotherapy or in&#xD;
           combination with amlodipine to reduce thr risk of heart failure (SIRRHF)&#xD;
&#xD;
        2. Medicine: spironolactone (20mg/tablet), indapamide (1.5mg/tablet) and amlodipine&#xD;
           (5mg/tablet).&#xD;
&#xD;
        3. Rationale: Our hypothesis of the present trial is that spironolactone is superior to&#xD;
           indapamide in cardiovascular prevention in hypertensive patients, with the possible&#xD;
           addition of amlodipine. Before a clinical outcome trial is considered, the present&#xD;
           feasibility trial is designed to compare the efficacy of antihypertensive regimens based&#xD;
           on these two drugs on blood pressure and several measurements of organ damage.&#xD;
&#xD;
        4. Objective: To evaluate the effects of spironolactone (either with or without&#xD;
           amlodipine), in comparison with indapamide (either with or without amlodipine), on the&#xD;
           extent of blood pressure reduction.&#xD;
&#xD;
        5. Study design: Multi-center (five sites), prospective, randomized, open-label,&#xD;
           blinded-end point study with active treatment arm (study duration - 12 weeks)&#xD;
&#xD;
        6. Study population: Men and Women aged over 45 years (n=200) meeting the&#xD;
           inclusion/exclusion criteria.&#xD;
&#xD;
        7. Randomization and treatment: After stratification by centers, eligible patients will be&#xD;
           randomly divided into two groups, taking spironolactone (20mg tablet) once a day or&#xD;
           indapamide (1.5mg tablet) once a day. Spironolactone may be up-titrated to 40mg daily&#xD;
           and indapamide may be up-titrated to 3mg daily at 4-week or 8-week visit. At 8-week&#xD;
           visit, if needed, we will add amlodipine at 5 or 10 mg once daily.&#xD;
&#xD;
        8. Follow up: 12 weeks.&#xD;
&#xD;
        9. Sample size: a total of 200 patients should be enrolled in the combination.&#xD;
&#xD;
       10. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in June&#xD;
           2020, recruitment will start. Patients enrollment will be performed between June 2020 to&#xD;
           November 2020. All patients should be followed up before July 2021.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Study name: The comparison between spironolactone and indapamide monotherapy or in&#xD;
           combination with amlodipine to reduce thr risk of heart failure (SIRRHF)&#xD;
&#xD;
        2. Medicine: spironolactone (20mg/tablet), indapamide (1.5mg/tablet) and amlodipine&#xD;
           (5mg/tablet).&#xD;
&#xD;
        3. Rationale: Our hypothesis of the present trial is that spironolactone is superior to&#xD;
           indapamide in cardiovascular prevention in hypertensive patients, with the possible&#xD;
           addition of amlodipine. Before a clinical outcome trial is considered, the present&#xD;
           feasibility trial is designed to compare the efficacy of antihypertensive regimens based&#xD;
           on these two drugs on blood pressure and several measurements of organ damage.&#xD;
&#xD;
        4. Objective: To evaluate the effects of spironolactone (either with or without&#xD;
           amlodipine), in comparison with indapamide (either with or without amlodipine), on the&#xD;
           extent of blood pressure reduction.&#xD;
&#xD;
        5. Study design: Multi-center (five sites), prospective, randomized, open-label,&#xD;
           blinded-end point study with active treatment arm (study duration - 12 weeks)&#xD;
&#xD;
        6. Study population: Men and Women aged over 45 years (n=200) meeting the&#xD;
           inclusion/exclusion criteria. Adult subjects with essential hypertension will be&#xD;
           included. Specific criteria are as follows:&#xD;
&#xD;
           Male and female subjects participates (OK with more women is preferred) Age ≥45 years&#xD;
           Clinic systolic BP: 140 -179 mmHg (untreated or on monotherapy treatment) Waist&#xD;
           Circumference (WC) ≥90 cm for male and ≥85 cm for female&#xD;
&#xD;
        7. Randomization and treatment: After stratification by centers, eligible patients will be&#xD;
           randomly divided into two groups, taking spironolactone (20mg tablet) once a day or&#xD;
           indapamide (1.5mg tablet) once a day. Spironolactone may be up-titrated to 40mg daily&#xD;
           and indapamide may be up-titrated to 3mg daily at 4-week or 8-week visit. At 8-week&#xD;
           visit, if needed, we will add amlodipine at 5 or 10 mg once daily.&#xD;
&#xD;
        8. Follow up: 12 weeks. Patients will be followed up every 4 weeks. Ambulatory and office&#xD;
           blood pressure will be measured. Medical history should be recorded. Clinical&#xD;
           examinations including blood biochemical tests (serum creatinine, uric acid and&#xD;
           electrolytes) should be performed.&#xD;
&#xD;
        9. Sample size: a total of 200 patients should be enrolled in the combination.&#xD;
&#xD;
       10. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in June&#xD;
           2020, recruitment will start. Patients enrollment will be performed between June 2020 to&#xD;
           November 2020. All patients should be followed up before July 2021.&#xD;
&#xD;
       11. Organization: The Centre for Epidemiological Studies and Clinical Trials, Ruijin&#xD;
           Hospital, Shanghai, China&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 23, 2020</start_date>
  <completion_date type="Anticipated">December 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2023</primary_completion_date>
  <phase>Phase 4</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>
    <intervention_model_description>Eligible patients will be randomly divided into two groups, taking spironolactone (20mg/tablet) once a day or indapamide (1.5mg/tablet) once a day.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>pulse wave velocity</measure>
    <time_frame>12 weeks</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>systolic blood pressure</measure>
    <time_frame>12 weeks</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>NT-proBNP</measure>
    <time_frame>12 weeks</time_frame>
    <description>NT-proBNP level will be measured by Roche Diagnostics.</description>
  </other_outcome>
  <other_outcome>
    <measure>Type I &amp; III procollagen</measure>
    <time_frame>12 weeks</time_frame>
    <description>Type I &amp; III procollagen level will be measured using a commercial ELISA kit</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Hypertension</condition>
  <arm_group>
    <arm_group_label>Spironolactone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Spironolactone 20mg once daily</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Indapamide</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Indapamide 1.5mg once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Spironolactone</intervention_name>
    <description>spironolactone 20mg once daily, up-titrated to 40mg once daily at 4-week or 8-week visit</description>
    <arm_group_label>Spironolactone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Indapamide</intervention_name>
    <description>indapamide 1.5mg once daily, up-titrated to 3mg once daily at 4-week or 8-week visit</description>
    <arm_group_label>Indapamide</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Adult subjects with essential hypertension will be included. Specific criteria are as&#xD;
        follows&#xD;
&#xD;
          1. Male and post menopause female subjects participates (OK with more women is preferred)&#xD;
&#xD;
          2. Age ≥45 years&#xD;
&#xD;
          3. Clinic systolic BP: 140 -179 mmHg (untreated or on monotherapy treatment)&#xD;
&#xD;
          4. Waist Circumference (WC) ≥90 cm for male and ≥85 cm for female&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Confirmed secondary hypertension&#xD;
&#xD;
          2. Hyperkalemia (serum potassium concentration ≥5.0 mmol/L) or hypokalemia (serum&#xD;
             potassium concentration ≤3.5 mmol/L)&#xD;
&#xD;
          3. Contraindication for the treatment drugs or current use of spironolactone, indapamide&#xD;
             or amlodipine&#xD;
&#xD;
          4. Chronic kidney disease (eGFR≤45 ml/min 1.73 m² or serum creatinine ≥ 2 mg/dl)&#xD;
&#xD;
          5. Expected lifespan ≤6 months&#xD;
&#xD;
          6. Treated subjects in whom withdrawal of antihypertensive treatment is deemed unethical&#xD;
             by the investigator (e.g. because of the existence of compelling indications other&#xD;
             than hypertension for continuous use of previously used antihypertensive agent)&#xD;
&#xD;
          7. Contraindications to study treatments as detailed in the relative Summaries of medical&#xD;
             Product Characteristics for spironolactone, indapamide or amlodipine (this includes&#xD;
             hypersensitivity, pregnancy and lactation)&#xD;
&#xD;
          8. Diagnosed cardiovascular diseases other than hypertension (coronary heart disease,&#xD;
             heart failure or left ventricular systolic dysfunction of any degree, atrial&#xD;
             fibrillation or frequent arrhythmias, valvular or congenital heart disease,&#xD;
             cardiomyopathies, cerebrovascular disease, peripheral artery disease, or aortic&#xD;
             aneurysm)&#xD;
&#xD;
          9. Subjects with conditions other than those mentioned above, where compelling&#xD;
             indications for the use of any specific class of antihypertensive medication exist,&#xD;
             according to the current (e.g. European Society of Cardiology) guidelines&#xD;
&#xD;
         10. Other conditions deemed relevant by the investigator (including respiratory disorders,&#xD;
             liver disease, renal disease, thyroid disorders)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>45 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Dongtai Renmin Hospital</name>
      <address>
        <city>Dongtai</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Feng Xue, MD</last_name>
      <phone>18066157759</phone>
      <email>18066157759@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Kunshan First Renmin Hospital</name>
      <address>
        <city>Kunshan</city>
        <state>Jiangsu</state>
        <country>China</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Ming Gu</last_name>
      <phone>15961676992</phone>
      <email>15962676992@126.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Changzhi Heping Hospital</name>
      <address>
        <city>Changzhi</city>
        <state>Shanxi</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Zhiping Wang, MD</last_name>
      <phone>13015462258</phone>
      <email>czhpwzp@163.com</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Shanghai Institite of Hypertension, Ruijin Hospital, Shanghai Jiaotong University School of Medicine</name>
      <address>
        <city>Shanghai</city>
        <zip>200025</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jiguang Wang, MD, PhD</last_name>
      <phone>86-21-64370045</phone>
      <phone_ext>610911</phone_ext>
      <email>jiguang_wang_jgw@yahoo.com</email>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>June 29, 2020</study_first_submitted>
  <study_first_submitted_qc>June 29, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 2, 2020</study_first_posted>
  <last_update_submitted>December 7, 2021</last_update_submitted>
  <last_update_submitted_qc>December 7, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">December 8, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Shanghai Jiao Tong University School of Medicine</investigator_affiliation>
    <investigator_full_name>Ji-Guang Wang</investigator_full_name>
    <investigator_title>Director of the Shanghai Institute of Hypertension</investigator_title>
  </responsible_party>
  <keyword>blood pressure</keyword>
  <keyword>spironolactone</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Heart Failure</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Indapamide</mesh_term>
    <mesh_term>Spironolactone</mesh_term>
  </intervention_browse>
  <!-- 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/NCT04455178
org study id: SIRRHF
nct id: NCT04455178
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
1. Study name: The comparison between spironolactone and indapamide monotherapy or in
           combination with amlodipine to reduce thr risk of heart failure (SIRRHF)

        2. Medicine: spironolactone (20mg/tablet), indapamide (1.5mg/tablet) and amlodipine
           (5mg/tablet).

        3. Rationale: Our hypothesis of the present trial is that spironolactone is superior to
           indapamide in cardiovascular prevention in hypertensive patients, with the possible
           addition of amlodipine. Before a clinical outcome trial is considered, the present
           feasibility trial is designed to compare the efficacy of antihypertensive regimens based
           on these two drugs on blood pressure and several measurements of organ damage.

        4. Objective: To evaluate the effects of spironolactone (either with or without
           amlodipine), in comparison with indapamide (either with or without amlodipine), on the
           extent of blood pressure reduction.

        5. Study design: Multi-center (five sites), prospective, randomized, open-label,
           blinded-end point study with active treatment arm (study duration - 12 weeks)

        6. Study population: Men and Women aged over 45 years (n=200) meeting the
           inclusion/exclusion criteria.

        7. Randomization and treatment: After stratification by centers, eligible patients will be
           randomly divided into two groups, taking spironolactone (20mg tablet) once a day or
           indapamide (1.5mg tablet) once a day. Spironolactone may be up-titrated to 40mg daily
           and indapamide may be up-titrated to 3mg daily at 4-week or 8-week visit. At 8-week
           visit, if needed, we will add amlodipine at 5 or 10 mg once daily.

        8. Follow up: 12 weeks.

        9. Sample size: a total of 200 patients should be enrolled in the combination.

       10. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in June
           2020, recruitment will start. Patients enrollment will be performed between June 2020 to
           November 2020. All patients should be followed up before July 2021.
1. Study name: The comparison between spironolactone and indapamide monotherapy or in
           combination with amlodipine to reduce thr risk of heart failure (SIRRHF)

        2. Medicine: spironolactone (20mg/tablet), indapamide (1.5mg/tablet) and amlodipine
           (5mg/tablet).

        3. Rationale: Our hypothesis of the present trial is that spironolactone is superior to
           indapamide in cardiovascular prevention in hypertensive patients, with the possible
           addition of amlodipine. Before a clinical outcome trial is considered, the present
           feasibility trial is designed to compare the efficacy of antihypertensive regimens based
           on these two drugs on blood pressure and several measurements of organ damage.

        4. Objective: To evaluate the effects of spironolactone (either with or without
           amlodipine), in comparison with indapamide (either with or without amlodipine), on the
           extent of blood pressure reduction.

        5. Study design: Multi-center (five sites), prospective, randomized, open-label,
           blinded-end point study with active treatment arm (study duration - 12 weeks)

        6. Study population: Men and Women aged over 45 years (n=200) meeting the
           inclusion/exclusion criteria. Adult subjects with essential hypertension will be
           included. Specific criteria are as follows:

           Male and female subjects participates (OK with more women is preferred) Age ≥45 years
           Clinic systolic BP: 140 -179 mmHg (untreated or on monotherapy treatment) Waist
           Circumference (WC) ≥90 cm for male and ≥85 cm for female

        7. Randomization and treatment: After stratification by centers, eligible patients will be
           randomly divided into two groups, taking spironolactone (20mg tablet) once a day or
           indapamide (1.5mg tablet) once a day. Spironolactone may be up-titrated to 40mg daily
           and indapamide may be up-titrated to 3mg daily at 4-week or 8-week visit. At 8-week
           visit, if needed, we will add amlodipine at 5 or 10 mg once daily.

        8. Follow up: 12 weeks. Patients will be followed up every 4 weeks. Ambulatory and office
           blood pressure will be measured. Medical history should be recorded. Clinical
           examinations including blood biochemical tests (serum creatinine, uric acid and
           electrolytes) should be performed.

        9. Sample size: a total of 200 patients should be enrolled in the combination.

       10. Timeline: After obtaining the approval of Ethics Committee of Ruijin Hospital in June
           2020, recruitment will start. Patients enrollment will be performed between June 2020 to
           November 2020. All patients should be followed up before July 2021.

       11. Organization: The Centre for Epidemiological Studies and Clinical Trials, Ruijin
           Hospital, Shanghai, China
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: Eligible patients will be randomly divided into two groups, taking spironolactone (20mg/tablet) once a day or indapamide (1.5mg/tablet) once a day.
primary purpose: Treatment
masking: None (Open Label)
measure: pulse wave velocity
time frame: 12 weeks
measure: systolic blood pressure
time frame: 12 weeks
measure: NT-proBNP
time frame: 12 weeks
description: NT-proBNP level will be measured by Roche Diagnostics.
measure: Type I & III procollagen
time frame: 12 weeks
description: Type I & III procollagen level will be measured using a commercial ELISA kit
arm group label: Spironolactone
arm group type: Experimental
description: Spironolactone 20mg once daily
arm group label: Indapamide
arm group type: Active Comparator
description: Indapamide 1.5mg once daily
intervention type: Drug
intervention name: Spironolactone
description: spironolactone 20mg once daily, up-titrated to 40mg once daily at 4-week or 8-week visit
arm group label: Spironolactone
intervention type: Drug
intervention name: Indapamide
description: indapamide 1.5mg once daily, up-titrated to 3mg once daily at 4-week or 8-week visit
arm group label: Indapamide
criteria: 
gender: All
minimum age: 45 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: China
responsible party type: Principal Investigator
investigator affiliation: Shanghai Jiao Tong University School of Medicine
investigator full name: Ji-Guang Wang
investigator title: Director of the Shanghai Institute of Hypertension
mesh term: Heart Failure
mesh term: Indapamide
mesh term: Spironolactone