<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/NCT03755700</url>
  </required_header>
  <id_info>
    <org_study_id>Intervention-01</org_study_id>
    <nct_id>NCT03755700</nct_id>
  </id_info>
  <brief_title>Vitamin E and N-acetylcysteine for Preventing Contrast-Induced Acute Kidney Injury After Coronary Artery Catheterization</brief_title>
  <official_title>Antioxidants for Preventing Contrast-Induced Acute Kidney Injury After Coronary Artery Catheterization</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rajaie Cardiovascular Medical and Research Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rajaie Cardiovascular Medical and Research Center</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>
      In a double-blinded randomized clinical trial, all patients undergoing coronary artery&#xD;
      catheterization who will met our criteria, will be enrolled into three groups to receive&#xD;
      either, vitamin e, n-acetylcysteine, or placebo. The aim of study will be to compare the&#xD;
      superiority of vitamin e over n-acetylcysteine for the prevention of contrast-induced acute&#xD;
      kidney injury (CIAKI).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Patients aged ≥18 years with chronic kidney disease who undergo coronary catheterization will&#xD;
      be enrolled into the study if they meet the inclusion criteria. Patients will be randomly&#xD;
      assigned into three groups in a 1:1:1 ratio (Computer-generated random number will be used to&#xD;
      assign a patient in either group): we will use simple randomization for assigning each&#xD;
      patient in a group. The participants, physicians and outcome assessors will be blinded&#xD;
      throughout the trial until the opening of the randomization cold.&#xD;
&#xD;
      All patients will be entered into three group and they will be given normal saline 0.9%,&#xD;
      vitamin E, NAC, and the placebos of both regimens. The vitamin E will be given as a soft gel&#xD;
      capsule and its placebo will have the same shape and taste. The NAC will be given as an&#xD;
      effervescent tablet with a glass of water for consumption and its placebo will also have the&#xD;
      same shape and taste. These drugs will be given in addition to the routine hydration therapy&#xD;
      which will be given to all patients.&#xD;
&#xD;
      Primary outcome will be the development of CIAKI. Secondary outcomes will be the development&#xD;
      of major adverse cardiovascular events and any events till evaluating the CIAKI within 48-72&#xD;
      hours after intervention.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 1, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2019</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2019</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>Prevention</primary_purpose>
    <masking>Double (Participant, Care Provider)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Contrast-induced acute kidney injury</measure>
    <time_frame>48 to 72 hours after coronary catheterization</time_frame>
    <description>Contrast-induced acute kidney injury defined as an absolute increase ≥0.5 mg/dL or a relative increase ≥25% over baseline serum creatinine concentration within 48-72 hours after administration of contrast media.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in the levels of serum creatinine</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Changes in serum creatinine after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>eGFR within 48-72 hours after coronary catheterization</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Changes in eGFR after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes in complete blood cell count components from baseline to follow-up</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Changes in complete blood cell count components after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Length of hospital stay</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Length of hospital stay</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Requirement for renal replacement therapies</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Requirement for renal replacement therapies, ie, any kind of dialysis or renal transplantation</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-procedure acute coronary syndrome (ACS) events</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Recurrent acute coronary syndrome after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-procedure cerebrovascular events</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Cerebrovascular events after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>In-hospital mortality</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>In-hospital mortality after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-procedure atrial fibrillation</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Atrial fibrillation after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Post-procedure bleeding</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Bleeding events after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulmonary embolism</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Pulmonary embolism after coronary artery catheterization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Re-intervention</measure>
    <time_frame>48-72 hours post-procedure</time_frame>
    <description>Repeated coronary artery catheterization</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">1000</enrollment>
  <condition>Coronary Artery Disease</condition>
  <condition>Coronary Artery Angiography</condition>
  <condition>Coronary Catheterization</condition>
  <condition>Contrast-induced Nephropathy</condition>
  <condition>Stable Angina</condition>
  <condition>Acute Coronary Syndrome</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with the placebos of both vitamin E and NAC (i.e. the placebo of vitamin E as a soft gel capsule and the placebo of NAC as an effervescent tablets along with a glass of water with the same consumption order used in the groups 2 and 3, respectively).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Vitamin E</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention plus the placebo of NAC with a consumption order similar to group 3.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>NAC</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention plus the placebo of vitamin E with the consumption order similar to group 2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Vitamin E</intervention_name>
    <description>As a gel capsule of vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention</description>
    <arm_group_label>Vitamin E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>N-acetyl cysteine</intervention_name>
    <description>As an effervescent tablets of NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention</description>
    <arm_group_label>NAC</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo oral capsule</intervention_name>
    <description>The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group</description>
    <arm_group_label>NAC</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebos</intervention_name>
    <description>The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group</description>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Vitamin E</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal Saline Flush, 0.9% Injectable Solution</intervention_name>
    <description>Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization</description>
    <arm_group_label>NAC</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_label>Vitamin E</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Patients aged ≥18 years with baseline estimated glomerular filtration rate (eGFR) &lt;60&#xD;
        mL/min per 1.73 m2 (based on the Modification of Diet in Renal Disease study group formula)&#xD;
        who undergo coronary catheterization (i.e. coronary angiography and percutaneous coronary&#xD;
        intervention [PCI]) will be invited to the study if they meet the inclusion criteria:&#xD;
        stable angina with ischemia and indication for coronary angiography, non-ST-segment&#xD;
        elevation (NSTE) acute coronary syndrome (ACS) requiring an early invasive strategy, and&#xD;
        patients undergoing elective PCI .&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        acute ST-segment elevation myocardial infarction, high-risk NSTE-ACS warranting emergency&#xD;
        coronary angiography (&lt;2 hours), cardiogenic shock, pulmonary edema, overt heart failure&#xD;
        and/or ejection fraction &lt;30%, ACS undergoing coronary angiography or angioplasty during&#xD;
        the previous 5 days, sensitivity to contrast medium, recent administration of contrast&#xD;
        medium for any reason, AKI, history of dialysis, pregnancy, newly prescribed angiotensin&#xD;
        converting enzyme inhibitors or angiotensin receptor blockers, bleeding and/or coagulopathy&#xD;
        diseases, and consumption of nephrotoxic drugs, vitamin E, vitamin C, or N-acetylcysteine&#xD;
        (NAC) at least 48 hours before intervention.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Yousef Rezaei, MD</last_name>
    <phone>+98 91 2623 1864</phone>
    <email>yousefrezaei1986@gmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Bahram Mohebbi, MD</last_name>
    <phone>+ 98 21 2392</phone>
    <phone_ext>2072</phone_ext>
    <email>roodbar@yahoo.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Rajaie cardiovascular medical and research center</name>
      <address>
        <city>Tehran</city>
        <zip>1995614331</zip>
        <country>Iran, Islamic Republic of</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Majid Maleki, MD</last_name>
      <phone>+98 21 2392</phone>
      <phone_ext>2043</phone_ext>
      <email>research@rhc.ac.ir</email>
    </contact>
  </location>
  <location_countries>
    <country>Iran, Islamic Republic of</country>
  </location_countries>
  <reference>
    <citation>Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-Term High-Dose Vitamin E to Prevent Contrast Medium-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Elective Coronary Angiography: A Randomized Placebo-Controlled Trial. J Am Heart Assoc. 2016 Mar 15;5(3):e002919. doi: 10.1161/JAHA.115.002919.</citation>
    <PMID>27068631</PMID>
  </reference>
  <reference>
    <citation>Rezaei Y, Hemila H. Vitamins E and C May Differ in Their Effect on Contrast-Induced Acute Kidney Injury. Am J Kidney Dis. 2017 May;69(5):708-709. doi: 10.1053/j.ajkd.2016.12.022. Epub 2017 Mar 6. No abstract available.</citation>
    <PMID>28279510</PMID>
  </reference>
  <verification_date>November 2018</verification_date>
  <study_first_submitted>November 25, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 29, 2018</last_update_submitted>
  <last_update_submitted_qc>November 29, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 30, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acute Kidney Injury</mesh_term>
    <mesh_term>Coronary Artery Disease</mesh_term>
    <mesh_term>Acute Coronary Syndrome</mesh_term>
    <mesh_term>Angina, Stable</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Vitamin E</mesh_term>
    <mesh_term>Acetylcysteine</mesh_term>
    <mesh_term>N-monoacetylcystine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03755700
org study id: Intervention-01
nct id: NCT03755700
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In a double-blinded randomized clinical trial, all patients undergoing coronary artery
      catheterization who will met our criteria, will be enrolled into three groups to receive
      either, vitamin e, n-acetylcysteine, or placebo. The aim of study will be to compare the
      superiority of vitamin e over n-acetylcysteine for the prevention of contrast-induced acute
      kidney injury (CIAKI).
Patients aged ≥18 years with chronic kidney disease who undergo coronary catheterization will
      be enrolled into the study if they meet the inclusion criteria. Patients will be randomly
      assigned into three groups in a 1:1:1 ratio (Computer-generated random number will be used to
      assign a patient in either group): we will use simple randomization for assigning each
      patient in a group. The participants, physicians and outcome assessors will be blinded
      throughout the trial until the opening of the randomization cold.

      All patients will be entered into three group and they will be given normal saline 0.9%,
      vitamin E, NAC, and the placebos of both regimens. The vitamin E will be given as a soft gel
      capsule and its placebo will have the same shape and taste. The NAC will be given as an
      effervescent tablet with a glass of water for consumption and its placebo will also have the
      same shape and taste. These drugs will be given in addition to the routine hydration therapy
      which will be given to all patients.

      Primary outcome will be the development of CIAKI. Secondary outcomes will be the development
      of major adverse cardiovascular events and any events till evaluating the CIAKI within 48-72
      hours after intervention.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Prevention
masking: Double (Participant, Care Provider)
measure: Contrast-induced acute kidney injury
time frame: 48 to 72 hours after coronary catheterization
description: Contrast-induced acute kidney injury defined as an absolute increase ≥0.5 mg/dL or a relative increase ≥25% over baseline serum creatinine concentration within 48-72 hours after administration of contrast media.
measure: Changes in the levels of serum creatinine
time frame: 48-72 hours post-procedure
description: Changes in serum creatinine after coronary artery catheterization
measure: eGFR within 48-72 hours after coronary catheterization
time frame: 48-72 hours post-procedure
description: Changes in eGFR after coronary artery catheterization
measure: Changes in complete blood cell count components from baseline to follow-up
time frame: 48-72 hours post-procedure
description: Changes in complete blood cell count components after coronary artery catheterization
measure: Length of hospital stay
time frame: 48-72 hours post-procedure
description: Length of hospital stay
measure: Requirement for renal replacement therapies
time frame: 48-72 hours post-procedure
description: Requirement for renal replacement therapies, ie, any kind of dialysis or renal transplantation
measure: Post-procedure acute coronary syndrome (ACS) events
time frame: 48-72 hours post-procedure
description: Recurrent acute coronary syndrome after coronary artery catheterization
measure: Post-procedure cerebrovascular events
time frame: 48-72 hours post-procedure
description: Cerebrovascular events after coronary artery catheterization
measure: In-hospital mortality
time frame: 48-72 hours post-procedure
description: In-hospital mortality after coronary artery catheterization
measure: Post-procedure atrial fibrillation
time frame: 48-72 hours post-procedure
description: Atrial fibrillation after coronary artery catheterization
measure: Post-procedure bleeding
time frame: 48-72 hours post-procedure
description: Bleeding events after coronary artery catheterization
measure: Pulmonary embolism
time frame: 48-72 hours post-procedure
description: Pulmonary embolism after coronary artery catheterization
measure: Re-intervention
time frame: 48-72 hours post-procedure
description: Repeated coronary artery catheterization
arm group label: Placebo
arm group type: Placebo Comparator
description: Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with the placebos of both vitamin E and NAC (i.e. the placebo of vitamin E as a soft gel capsule and the placebo of NAC as an effervescent tablets along with a glass of water with the same consumption order used in the groups 2 and 3, respectively).
arm group label: Vitamin E
arm group type: Active Comparator
description: Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention plus the placebo of NAC with a consumption order similar to group 3.
arm group label: NAC
arm group type: Active Comparator
description: Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization combined with NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention plus the placebo of vitamin E with the consumption order similar to group 2.
intervention type: Drug
intervention name: Vitamin E
description: As a gel capsule of vitamin E 800 IU orally 2 hours before intervention and 400 IU orally 4 hours after intervention
arm group label: Vitamin E
intervention type: Drug
intervention name: N-acetyl cysteine
description: As an effervescent tablets of NAC 1200 mg orally 2 hours before intervention and 1200 mg orally 4 hours after intervention
arm group label: NAC
intervention type: Drug
intervention name: Placebo oral capsule
description: The placebo of vitamin E as a soft gel capsule with the consumption order similar to vitamin e group
arm group label: NAC
arm group label: Placebo
intervention type: Drug
intervention name: Placebos
description: The placebo of n-acetylcysteine as a tablet with the consumption order similar to n-acetylcysteine group
arm group label: Placebo
arm group label: Vitamin E
intervention type: Drug
intervention name: Normal Saline Flush, 0.9% Injectable Solution
description: Normal saline 0.9% infusions (1 mL/kg) for 12 hours prior to and after coronary catheterization
arm group label: NAC
arm group label: Placebo
arm group label: Vitamin E
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Yousef Rezaei, MD
phone: +98 91 2623 1864
email: yousefrezaei1986@gmail.com
last name: Bahram Mohebbi, MD
phone: + 98 21 2392
phone ext: 2072
email: roodbar@yahoo.com
facility: 
status: Recruiting
contact: 
country: Iran, Islamic Republic of
citation: Rezaei Y, Khademvatani K, Rahimi B, Khoshfetrat M, Arjmand N, Seyyed-Mohammadzad MH. Short-Term High-Dose Vitamin E to Prevent Contrast Medium-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Elective Coronary Angiography: A Randomized Placebo-Controlled Trial. J Am Heart Assoc. 2016 Mar 15;5(3):e002919. doi: 10.1161/JAHA.115.002919.
PMID: 27068631
citation: Rezaei Y, Hemila H. Vitamins E and C May Differ in Their Effect on Contrast-Induced Acute Kidney Injury. Am J Kidney Dis. 2017 May;69(5):708-709. doi: 10.1053/j.ajkd.2016.12.022. Epub 2017 Mar 6. No abstract available.
PMID: 28279510
responsible party type: Sponsor
mesh term: Acute Kidney Injury
mesh term: Coronary Artery Disease
mesh term: Acute Coronary Syndrome
mesh term: Angina, Stable
mesh term: Vitamin E
mesh term: Acetylcysteine
mesh term: N-monoacetylcystine
sharing ipd: Undecided