<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/NCT01667614</url>
  </required_header>
  <id_info>
    <org_study_id>90-2-27-16-10</org_study_id>
    <nct_id>NCT01667614</nct_id>
  </id_info>
  <brief_title>Effects of Spironolactone Combination Therapy on Proteinuria, Kidney Function, and Blood Pressure</brief_title>
  <official_title>Comparison of Efficacy of Losartan/Spironolactone and Losartan/Enalapril on Urinary Albumin Excretion, Estimated Glomerular Filtration Rate, and Blood Pressure in Patients With Type 2 Diabetes Nephropathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Tehran University of Medical Sciences</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Tehran University of Medical Sciences</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The detrimental effects of aldostrone are not adequately arrested by the use of angiotensin&#xD;
      converting enzyme (ACE), angiotensin II receptor blocker (ARB) or a combination of both.&#xD;
      Recent evidence has provided robust evidence that aldostrone escape plays an important role&#xD;
      in this regard. It is believed that aldostrone escape occurs quite commonly with reports&#xD;
      indicating prevalence rates as high as 22% with ARBs and 40% with ACE inhibitors. In a trial&#xD;
      of patients with diabetes and hypertension it was shown that treatment of aldostrone escape&#xD;
      with spironolactone 25 mg daily for three months significantly reduces proteinuria. A number&#xD;
      of other trials have similarly observed that addition of spironolactone to an ACE inhibitor&#xD;
      based regimen provides additional benefits on proteinuria reduction, blood pressure control,&#xD;
      and prevention of glomerular filtration rate (GFR) decline. Most of the available trials in&#xD;
      this regard are of short duration (e.g. three months), and have added spironolactone to an&#xD;
      ACE or ACE+ARB based regimen (the so-called triple blockade). Currently, evidence evaluating&#xD;
      efficacy of a combined ARB+spironolactone regimen compared with conventional double RAS&#xD;
      blockade (i.e. ACE+ARB) is lacking. Hence, this randomized open label trial was initiated to&#xD;
      determine the effects of addition of spironolactone 25 mg daily to losartan over a period of&#xD;
      18 months.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>May 2010</start_date>
  <completion_date type="Actual">July 2012</completion_date>
  <primary_completion_date type="Actual">March 2012</primary_completion_date>
  <phase>Phase 2</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>Urinary albumin excretion</measure>
    <time_frame>18 months</time_frame>
    <description>Urinary albumin excretion assessed by overnight (12 hour) collection of urine. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>estimated glomerular filtration rate</measure>
    <time_frame>18 months</time_frame>
    <description>estimated glomerular filtration rate calculated using the formula developed by Chronic Kidney Disease Epidemiology Collaboration. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>18 months</time_frame>
    <description>Systolic and diastolic blood pressure assessed by mercury sphygnomanometry. Patients were placed in a sitting position and after ten minutes rest, two readings from right-side hand with five minutes interval were obtained. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>serum creatinine concentrations</measure>
    <time_frame>18 months</time_frame>
    <description>serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Serum potassium concentrations</measure>
    <time_frame>18 months</time_frame>
    <description>Serum potassium concentrations measured at baseline, 1st month, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">136</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <condition>Diabetic Nephropathy</condition>
  <condition>Essential Hypertension</condition>
  <arm_group>
    <arm_group_label>ACE/ARB</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>In 62 patients previously treated with enalapril (10-30 mg daily) + losartan (50-100 mg daily), this regimen was continued.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Spironolactone/ARB</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>spironolacone 25 mg tablets added to losartan</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>spironolacone 25 mg tablets added to losartan</intervention_name>
    <description>spironolactone 25 mg once daily added to losartan</description>
    <arm_group_label>Spironolactone/ARB</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  type 2 diabetes patients with diabetic nephropathy in the range of micro- or&#xD;
             macroalbuminuria&#xD;
&#xD;
          -  treatment with combination of enalapril and losartan for more than one year&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  history of non-adherence to prescribed medication assessed by the prescribing&#xD;
             physician&#xD;
&#xD;
          -  baseline potassium &gt; 5.5 meq/L&#xD;
&#xD;
          -  chronic kidney disease stages 4 or 5&#xD;
&#xD;
          -  history or evidence of non-diabetic kidney disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Alireza Esteghamati, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Tehran University of Medical Sciences</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Tehran University of Medical Sciences, Vali-asr hospital, Endocrinology and Metabolism Research Center</name>
      <address>
        <city>Tehran</city>
        <zip>13145-784</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <verification_date>August 2012</verification_date>
  <study_first_submitted>August 15, 2012</study_first_submitted>
  <study_first_submitted_qc>August 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 17, 2012</study_first_posted>
  <last_update_submitted>August 27, 2012</last_update_submitted>
  <last_update_submitted_qc>August 27, 2012</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 28, 2012</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Tehran University of Medical Sciences</investigator_affiliation>
    <investigator_full_name>Alireza Esteghamati</investigator_full_name>
    <investigator_title>Professor Alireza Esteghamati</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Kidney Diseases</mesh_term>
    <mesh_term>Diabetic Nephropathies</mesh_term>
    <mesh_term>Essential Hypertension</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Losartan</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/NCT01667614
org study id: 90-2-27-16-10
nct id: NCT01667614
lead sponsor: 
has dmc: No
The detrimental effects of aldostrone are not adequately arrested by the use of angiotensin
      converting enzyme (ACE), angiotensin II receptor blocker (ARB) or a combination of both.
      Recent evidence has provided robust evidence that aldostrone escape plays an important role
      in this regard. It is believed that aldostrone escape occurs quite commonly with reports
      indicating prevalence rates as high as 22% with ARBs and 40% with ACE inhibitors. In a trial
      of patients with diabetes and hypertension it was shown that treatment of aldostrone escape
      with spironolactone 25 mg daily for three months significantly reduces proteinuria. A number
      of other trials have similarly observed that addition of spironolactone to an ACE inhibitor
      based regimen provides additional benefits on proteinuria reduction, blood pressure control,
      and prevention of glomerular filtration rate (GFR) decline. Most of the available trials in
      this regard are of short duration (e.g. three months), and have added spironolactone to an
      ACE or ACE+ARB based regimen (the so-called triple blockade). Currently, evidence evaluating
      efficacy of a combined ARB+spironolactone regimen compared with conventional double RAS
      blockade (i.e. ACE+ARB) is lacking. Hence, this randomized open label trial was initiated to
      determine the effects of addition of spironolactone 25 mg daily to losartan over a period of
      18 months.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Urinary albumin excretion
time frame: 18 months
description: Urinary albumin excretion assessed by overnight (12 hour) collection of urine. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
measure: estimated glomerular filtration rate
time frame: 18 months
description: estimated glomerular filtration rate calculated using the formula developed by Chronic Kidney Disease Epidemiology Collaboration. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
measure: Blood pressure
time frame: 18 months
description: Systolic and diastolic blood pressure assessed by mercury sphygnomanometry. Patients were placed in a sitting position and after ten minutes rest, two readings from right-side hand with five minutes interval were obtained. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
measure: serum creatinine concentrations
time frame: 18 months
description: serum creatinine concentrations assessed by Jaffe method. Measured at baseline, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
measure: Serum potassium concentrations
time frame: 18 months
description: Serum potassium concentrations measured at baseline, 1st month, 3rd month, 6th month, 9th month, 12th month, 15th month, and 18th month.
arm group label: ACE/ARB
arm group type: No Intervention
description: In 62 patients previously treated with enalapril (10-30 mg daily) + losartan (50-100 mg daily), this regimen was continued.
arm group label: Spironolactone/ARB
arm group type: Active Comparator
description: spironolacone 25 mg tablets added to losartan
intervention type: Drug
intervention name: spironolacone 25 mg tablets added to losartan
description: spironolactone 25 mg once daily added to losartan
arm group label: Spironolactone/ARB
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: No
last name: Alireza Esteghamati, M.D.
role: Principal Investigator
affiliation: Tehran University of Medical Sciences
facility: 
country: Iran, Islamic Republic of
responsible party type: Principal Investigator
investigator affiliation: Tehran University of Medical Sciences
investigator full name: Alireza Esteghamati
investigator title: Professor Alireza Esteghamati
mesh term: Kidney Diseases
mesh term: Diabetic Nephropathies
mesh term: Essential Hypertension
mesh term: Diabetes Mellitus, Type 2
mesh term: Losartan