<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/NCT01662895</url>
  </required_header>
  <id_info>
    <org_study_id>2012P-000005</org_study_id>
    <secondary_id>U01NS074425</secondary_id>
    <nct_id>NCT01662895</nct_id>
  </id_info>
  <brief_title>High-Dose Deferoxamine in Intracerebral Hemorrhage</brief_title>
  <acronym>HI-DEF</acronym>
  <official_title>Futility Study of Deferoxamine in Intracerebral Hemorrhage</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beth Israel Deaconess Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tufts Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Massachusetts, Worcester</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Pennsylvania</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Johns Hopkins University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Duke University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of North Carolina</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Florida</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Cleveland Clinic</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Henry Ford Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Ohio State University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>St. Joseph's Hospital and Medical Center, Phoenix</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Oregon Health and Science University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Yale New Haven Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Iowa</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hartford Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The University of Texas Health Science Center, Houston</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Rhode Island Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Stanford University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Washington</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Calgary</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Hopital de l'Enfant-Jesus</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Alberta</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Dalhousie University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Beth Israel Deaconess Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The main purpose of this study is to determine whether treatment with deferoxamine mesylate&#xD;
      is of sufficient promise to improve outcome before pursuing a larger clinical trial to&#xD;
      examine its effectiveness as a treatment for brain hemorrhage.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Several studies show that hemoglobin breakdown and subsequent iron accumulation in the brain&#xD;
      play a role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH); and&#xD;
      that treatment with the iron chelator, deferoxamine (DFO), provides neuroprotection in animal&#xD;
      models of ICH. The investigators recently concluded a phase-I, safety and dose-finding study&#xD;
      of DFO in patients with ICH; repeated daily intravenous (IV) infusions of DFO in doses up to&#xD;
      62 mg/kg/day (up to a maximum daily dose of 6000 mg/day) were well-tolerated and did not&#xD;
      increase serious adverse events or mortality. The current study builds on these results to&#xD;
      assess the potential utility of DFO as a therapeutic intervention in ICH.&#xD;
&#xD;
      This is a prospective, multi-center, double-blind, randomized, placebo-armed, phase-II,&#xD;
      futility clinical study to determine if this maximum tolerated dose of DFO is of sufficient&#xD;
      promise to improve outcome prior to embarking on a large-scale and costly phase III study to&#xD;
      assess its efficacy in ICH. The investigators will randomize 324 subjects with ICH equally&#xD;
      (1:1) to either DFO at 62 mg/kg/day (up to a maximum daily dose of 6000 mg/day), or saline&#xD;
      placebo, given by continuous IV infusion for 5 consecutive days. Treatment will be initiated&#xD;
      within 24 hours after ICH symptom onset. Subjects will be stratified based on baseline ICH&#xD;
      score (0-2 vs. 3-5) and ICH onset-to-treatment time (OTT) window (≤12h vs. &gt;12-24h), so that&#xD;
      the resulting randomization ratio is 1:1 within each ICH score and OTT window strata.&#xD;
&#xD;
      The main objectives are:&#xD;
&#xD;
        1. To assess whether it would be futile to move DFO forward into a Phase III trial based on&#xD;
           the end point of good outcome (defined as dichotomized modified Rankin Scale score of&#xD;
           0-2 at 3 months). At the conclusion of the study, the proportion of DFO-treated subjects&#xD;
           with a good outcome will be compared to the placebo proportion in a futility analysis.&#xD;
           If the DFO-treated proportion is less than 12% greater than the placebo proportion, then&#xD;
           it would be futile to move DFO forward to future Phase III testing.&#xD;
&#xD;
        2. To collect more data on treatment-related adverse events in order to ascertain that&#xD;
           patients with ICH can tolerate this dose given over an extended 5-day duration of&#xD;
           infusion without experiencing unreasonable neurological complications, increased&#xD;
           mortality, or other serious adverse events related to DFO use.&#xD;
&#xD;
      Secondary and exploratory objectives include:&#xD;
&#xD;
      1- Determining the overall distribution of scores on mRS at 3 months in DFO-treated subjects,&#xD;
      and to perform a dichotomized analysis considering the proportion of DFO- and placebo-treated&#xD;
      subjects with mRS 0-3.&#xD;
&#xD;
      Successful completion of this study will provide a crucial &quot;go/no-go&quot; signal for DFO in ICH.&#xD;
      Futility will discourage a major phase III trial, whereas non-futility will offer strong&#xD;
      support for a phase III study to detect clinical efficacy. Results from this study can&#xD;
      provide valuable information to guide the design and sample size estimation of a potential&#xD;
      future Phase III trial. ICH is a frequent cause of disability and death. A successful study&#xD;
      demonstrating the efficacy of DFO would be of considerable public health significance.&#xD;
&#xD;
      Update: Enrollment into the trial was terminated by the Data and Safety Monitoring Board&#xD;
      because of an imbalance in subjects with reported ARDS. At the time of termination, 42&#xD;
      subjects had been enrolled. As a result, any formal evaluation of these objectives would be&#xD;
      under-powered, but descriptive statistics are provided. The protocol was subsequently&#xD;
      modified to protect subject safety, and the trial was re-initiated as iDEF (NCT02175225).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    By DSMB on October 18, 2013 due to increased incidence of ARDS. See modified protocol&#xD;
    [NCT02175225&#xD;
  </why_stopped>
  <start_date type="Actual">March 18, 2013</start_date>
  <completion_date type="Actual">May 10, 2018</completion_date>
  <primary_completion_date type="Actual">January 15, 2014</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>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Subjects With Modified Rankin Scale (mRS) Score 0-2</measure>
    <time_frame>90 days</time_frame>
    <description>The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days.&#xD;
The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Subjects With mRS Score 0-3</measure>
    <time_frame>90 days</time_frame>
    <description>The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Number of Subjects With Allergic/Anaphylactic Reaction</measure>
    <time_frame>within 7 days or discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Patients With Hypotension</measure>
    <time_frame>within 7 days or discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Patients With New Visual or Auditory Changes</measure>
    <time_frame>within 7 days or discharge</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Patients With Serious Adverse Events</measure>
    <time_frame>90 days</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Number of Patients Who Died During the 90-day Study Period</measure>
    <time_frame>90 days</time_frame>
    <description>Mortality at any time from randomization through day-90</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">42</enrollment>
  <condition>Intracerebral Hemorrhage</condition>
  <arm_group>
    <arm_group_label>Deferoxamine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Normal Saline</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>0.9% sodium chloride</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Deferoxamine</intervention_name>
    <description>Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
    <arm_group_label>Deferoxamine</arm_group_label>
    <other_name>Deferoxamine Mesylate</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Normal saline</intervention_name>
    <description>This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
    <arm_group_label>Normal Saline</arm_group_label>
    <other_name>0.90% Sodium Chloride Solution</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age ≥ 18 and ≤ 80 years&#xD;
&#xD;
          2. The diagnosis of ICH is confirmed by brain CT scan&#xD;
&#xD;
          3. NIHSS score ≥ 6 and GCS &gt; 6 upon presentation&#xD;
&#xD;
          4. The first dose of the study drug can be administered within 24h of ICH symptom onset&#xD;
&#xD;
          5. Functional independence prior to ICH, defined as pre-ICH mRS ≤ 1&#xD;
&#xD;
          6. Signed and dated informed consent is obtained.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Previous chelation therapy or known hypersensitivity to DFO products&#xD;
&#xD;
          2. Known severe iron deficiency anemia (defined as hemoglobin concentration &lt; 7g/dL or&#xD;
             requiring blood transfusions)&#xD;
&#xD;
          3. Abnormal renal function, defined as serum creatinine &gt; 2 mg/dL&#xD;
&#xD;
          4. Planned surgical evacuation of ICH prior to administration of study drug (placement of&#xD;
             a catheter for ventricular drainage is not a contraindication to enrollment)&#xD;
&#xD;
          5. Suspected secondary ICH related to tumour, ruptured aneurysm or arteriovenous&#xD;
             malformation, hemorrhagic transformation of an ischemic infarct, or venous sinus&#xD;
             thrombosis&#xD;
&#xD;
          6. Infratentorial hemorrhage&#xD;
&#xD;
          7. Irreversibly impaired brainstem function (bilateral fixed and dilated pupils and&#xD;
             extensor motor posturing)&#xD;
&#xD;
          8. Complete unconsciousness, defined as a score of 3 on item 1a of the NIHSS (Responds&#xD;
             only with reflex motor or autonomic effects or totally unresponsive, and flaccid)&#xD;
&#xD;
          9. Pre-existing disability, defined as pre-ICH mRS ≥ 2&#xD;
&#xD;
         10. Coagulopathy - defined as elevated aPTT or INR &gt;1.3 upon presentation; concurrent use&#xD;
             of direct thrombin inhibitors (such as dabigatran), direct factor Xa inhibitors (such&#xD;
             as rivaroxaban), or low-molecular-weight heparin&#xD;
&#xD;
         11. Taking iron supplements containing ≥ 325 mg of ferrous iron, or prochlorperazine&#xD;
&#xD;
         12. Patients with heart failure taking &gt; 500 mg of vitamin C daily&#xD;
&#xD;
         13. Known severe hearing loss&#xD;
&#xD;
         14. Known pregnancy, or positive pregnancy test, or breastfeeding&#xD;
&#xD;
         15. Patients known or suspected of not being able to comply with the study protocol due to&#xD;
             alcoholism, drug dependency, noncompliance, living in another state or any other cause&#xD;
&#xD;
         16. Positive drug screen for cocaine upon presentation&#xD;
&#xD;
         17. Any condition which, in the judgement of the investigator, might increase the risk to&#xD;
             the patient&#xD;
&#xD;
         18. Life expectancy of less than 90 days due to comorbid conditions&#xD;
&#xD;
         19. Concurrent participation in another research protocol for investigation of another&#xD;
             experimental therapy&#xD;
&#xD;
         20. Indication that a new Do Not Resuscitate (DNR) or Comfort Measures Only (CMO) order&#xD;
             will be implemented within the first 72 hours of hospitalization.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Magdy Selim, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beth Israel Deaconess Medical Center/Harvard Medical School</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>St. Joseph's Hospital</name>
      <address>
        <city>Phoenix</city>
        <state>Arizona</state>
        <zip>85013</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Stanford University Hospital</name>
      <address>
        <city>Palo Alto</city>
        <state>California</state>
        <zip>94304</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hartford Hospital</name>
      <address>
        <city>Hartford</city>
        <state>Connecticut</state>
        <zip>06107</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yale New Haven Hospital</name>
      <address>
        <city>New Haven</city>
        <state>Connecticut</state>
        <zip>06510</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Florida College of Medicine</name>
      <address>
        <city>Jacksonville</city>
        <state>Florida</state>
        <zip>32209</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Iowa Hospital</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical Center</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tufts Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02111</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Massachusetts Memorial Medical Center</name>
      <address>
        <city>Worcester</city>
        <state>Massachusetts</state>
        <zip>01655</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henry Ford Hospital</name>
      <address>
        <city>Detroit</city>
        <state>Michigan</state>
        <zip>48202</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of North Carolina Medical Center</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27514</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Duke University Hospital</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Cleveland Clinic Foundation</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44195</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State University Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Oregon Health &amp; Science University</name>
      <address>
        <city>Portland</city>
        <state>Oregon</state>
        <zip>97239</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Pennsylvania Medical Center</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rhode Island Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The University of Texas Health Science Center</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Virginia Health System</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Harborview Medical Center</name>
      <address>
        <city>Seattle</city>
        <state>Washington</state>
        <zip>98104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Foothills Medical Center</name>
      <address>
        <city>Calgary</city>
        <state>Alberta</state>
        <zip>T2N 2T9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Mackenzie Health Sciences Centre</name>
      <address>
        <city>Edmonton</city>
        <state>Alberta</state>
        <zip>T6G 2B7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Halifax Infirmary</name>
      <address>
        <city>Halifax</city>
        <state>Nova Scotia</state>
        <zip>B3H 3A7</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hôpital de l'Enfant-Jésus - CHU de Québec</name>
      <address>
        <city>Québec</city>
        <zip>G1J 1Z4</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009 Mar;40(3 Suppl):S90-1. doi: 10.1161/STROKEAHA.108.533125. Epub 2008 Dec 8.</citation>
    <PMID>19064798</PMID>
  </reference>
  <reference>
    <citation>Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, Palesch Y; Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011 Nov;42(11):3067-74. doi: 10.1161/STROKEAHA.111.617589. Epub 2011 Aug 25.</citation>
    <PMID>21868742</PMID>
  </reference>
  <reference>
    <citation>Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009 Jun;40(6):2241-3. doi: 10.1161/STROKEAHA.108.539536. Epub 2009 Apr 16.</citation>
    <PMID>19372448</PMID>
  </reference>
  <reference>
    <citation>Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.</citation>
    <PMID>19286595</PMID>
  </reference>
  <verification_date>May 2019</verification_date>
  <study_first_submitted>July 30, 2012</study_first_submitted>
  <study_first_submitted_qc>August 8, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 13, 2012</study_first_posted>
  <results_first_submitted>May 8, 2019</results_first_submitted>
  <results_first_submitted_qc>May 29, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">May 30, 2019</results_first_posted>
  <last_update_submitted>May 29, 2019</last_update_submitted>
  <last_update_submitted_qc>May 29, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">June 12, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beth Israel Deaconess Medical Center</investigator_affiliation>
    <investigator_full_name>Magdy Selim</investigator_full_name>
    <investigator_title>Professor of Neurology</investigator_title>
  </responsible_party>
  <keyword>Brain hemorrhage</keyword>
  <keyword>Cerebral Hemorrhage</keyword>
  <keyword>Deferoxamine</keyword>
  <keyword>Hi-DEF Trial</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebral Hemorrhage</mesh_term>
    <mesh_term>Hemorrhage</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Deferoxamine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Deferoxamine</title>
          <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
        <group group_id="P2">
          <title>Normal Saline</title>
          <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Initiated Study Drug</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Deferoxamine</title>
          <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
        <group group_id="B2">
          <title>Normal Saline</title>
          <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="21"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="42"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Median</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="64" lower_limit="35" upper_limit="77"/>
                    <measurement group_id="B2" value="64" lower_limit="43" upper_limit="77"/>
                    <measurement group_id="B3" value="64" lower_limit="35" upper_limit="77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="14"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="39"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Subjects With Modified Rankin Scale (mRS) Score 0-2</title>
        <description>The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days.&#xD;
The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Modified Rankin Scale (mRS) Score 0-2</title>
          <description>The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days.&#xD;
The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Subjects With mRS Score 0-3</title>
        <description>The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With mRS Score 0-3</title>
          <description>The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12"/>
                    <measurement group_id="O2" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Subjects With Allergic/Anaphylactic Reaction</title>
        <time_frame>within 7 days or discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Allergic/Anaphylactic Reaction</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Patients With Hypotension</title>
        <time_frame>within 7 days or discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Hypotension</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Patients With New Visual or Auditory Changes</title>
        <time_frame>within 7 days or discharge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With New Visual or Auditory Changes</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Patients With Serious Adverse Events</title>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients With Serious Adverse Events</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                    <measurement group_id="O2" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Number of Patients Who Died During the 90-day Study Period</title>
        <description>Mortality at any time from randomization through day-90</description>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Patients Who Died During the 90-day Study Period</title>
          <description>Mortality at any time from randomization through day-90</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Post-Hoc</type>
        <title>Number of Subjects With Acute Respiratory Distress Syndrome</title>
        <time_frame>90 days</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Deferoxamine</title>
            <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
          <group group_id="O2">
            <title>Normal Saline</title>
            <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Subjects With Acute Respiratory Distress Syndrome</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>All adverse events (serious and non-serious) were assessed until day-7 or discharge, whichever occurs earlier, and serious adverse events until day-90 (i.e. completion of the study) or withdrawal of consent.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Deferoxamine</title>
          <description>Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.&#xD;
Deferoxamine: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
        <group group_id="E2">
          <title>Normal Saline</title>
          <description>0.9% sodium chloride&#xD;
Normal saline: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="9" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Systemic inflammatory response syndrome</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Intracranial hypotension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Ischaemic cerebral infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neurological decompensation</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Renal failure</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoxia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Increased bronchial secretion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pneumonia aspiration</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Respiratory failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Upper airway obstruction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>MedDRA (15.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="17" subjects_at_risk="21"/>
                <counts group_id="E2" subjects_affected="18" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Anaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Coagulopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Leukocytosis</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Thrombocytopenia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Cardiopulmonary failure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinus bradycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Tachycardia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Ear and labyrinth disorders</title>
            <event_list>
              <event>
                <sub_title>Tinnitus</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Colour blindness acquired</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pupils unequal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Abdominal distension</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Abdominal pain lower</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Diarrhoea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysphagia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Vomiting</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Chest pain</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hyperthermia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion site erythema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion site extravasation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion site inflammation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion site oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Infusion site pain</sub_title>
                <counts group_id="E1" events="2" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pyrexia</sub_title>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="21"/>
                <counts group_id="E2" events="7" subjects_affected="6" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Ischaemic hepatitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacteraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Clostridial infection</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Meningitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sinusitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E2" events="4" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Investigations</title>
            <event_list>
              <event>
                <sub_title>Alanine aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Aspartate aminotransferase increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood creatinine abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood creatinine increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood glucose increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood iron decreased</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood magnesium increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood urea abnormal</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Blood urea increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Cardiac enzymes increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Electrocardiogram QT prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Haemoglobin decreased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>International normalised ratio increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Iron binding capacity total decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Prothrombin time</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Prothrombin time prolonged</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Renal function test abnormal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Serum ferritin abnormal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Transferrin decreased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Troponin increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Urine analysis abnormal</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>White blood cell count increased</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Electrolyte imbalance</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Fluid overload</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hyperglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypernatraemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypocalcaemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypokalaemia</sub_title>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hyponatraemia</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="21"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hypophosphataemia</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Metabolic acidosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscle spasms</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pain in extremity</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Brain oedema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Hydrocephalus</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Intracranial pressure increased</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Intraventricular haemorrhage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Ischaemic stroke</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Neurological decompensation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Subarachnoid haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Delirium</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Depression</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Mental status changes</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Haematuria</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Renal failure acute</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Ureteric dilatation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Acute respiratory distress syndrome</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Atelectasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Cough</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pleural effusion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pulmonary embolism</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Pulmonary oedema</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Skin disorder</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Hypotension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="21"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Phlebitis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="21"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>The study was terminated prematurely, and only 42 subjects were enrolled. As a result, any formal evaluation of these outcomes would be under-powered. Only descriptive statistics are provided.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Magdy Selim, MD, PhD</name_or_title>
      <organization>Beth Israel Deaconess Medical Center</organization>
      <phone>617-63208913</phone>
      <email>mselim@bidmc.harvard.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01662895
org study id: 2012P-000005
secondary id: U01NS074425
nct id: NCT01662895
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has dmc: Yes
The main purpose of this study is to determine whether treatment with deferoxamine mesylate
      is of sufficient promise to improve outcome before pursuing a larger clinical trial to
      examine its effectiveness as a treatment for brain hemorrhage.
Several studies show that hemoglobin breakdown and subsequent iron accumulation in the brain
      play a role in mediating secondary neuronal injury after intracerebral hemorrhage (ICH); and
      that treatment with the iron chelator, deferoxamine (DFO), provides neuroprotection in animal
      models of ICH. The investigators recently concluded a phase-I, safety and dose-finding study
      of DFO in patients with ICH; repeated daily intravenous (IV) infusions of DFO in doses up to
      62 mg/kg/day (up to a maximum daily dose of 6000 mg/day) were well-tolerated and did not
      increase serious adverse events or mortality. The current study builds on these results to
      assess the potential utility of DFO as a therapeutic intervention in ICH.

      This is a prospective, multi-center, double-blind, randomized, placebo-armed, phase-II,
      futility clinical study to determine if this maximum tolerated dose of DFO is of sufficient
      promise to improve outcome prior to embarking on a large-scale and costly phase III study to
      assess its efficacy in ICH. The investigators will randomize 324 subjects with ICH equally
      (1:1) to either DFO at 62 mg/kg/day (up to a maximum daily dose of 6000 mg/day), or saline
      placebo, given by continuous IV infusion for 5 consecutive days. Treatment will be initiated
      within 24 hours after ICH symptom onset. Subjects will be stratified based on baseline ICH
      score (0-2 vs. 3-5) and ICH onset-to-treatment time (OTT) window (≤12h vs. >12-24h), so that
      the resulting randomization ratio is 1:1 within each ICH score and OTT window strata.

      The main objectives are:

        1. To assess whether it would be futile to move DFO forward into a Phase III trial based on
           the end point of good outcome (defined as dichotomized modified Rankin Scale score of
           0-2 at 3 months). At the conclusion of the study, the proportion of DFO-treated subjects
           with a good outcome will be compared to the placebo proportion in a futility analysis.
           If the DFO-treated proportion is less than 12% greater than the placebo proportion, then
           it would be futile to move DFO forward to future Phase III testing.

        2. To collect more data on treatment-related adverse events in order to ascertain that
           patients with ICH can tolerate this dose given over an extended 5-day duration of
           infusion without experiencing unreasonable neurological complications, increased
           mortality, or other serious adverse events related to DFO use.

      Secondary and exploratory objectives include:

      1- Determining the overall distribution of scores on mRS at 3 months in DFO-treated subjects,
      and to perform a dichotomized analysis considering the proportion of DFO- and placebo-treated
      subjects with mRS 0-3.

      Successful completion of this study will provide a crucial "go/no-go" signal for DFO in ICH.
      Futility will discourage a major phase III trial, whereas non-futility will offer strong
      support for a phase III study to detect clinical efficacy. Results from this study can
      provide valuable information to guide the design and sample size estimation of a potential
      future Phase III trial. ICH is a frequent cause of disability and death. A successful study
      demonstrating the efficacy of DFO would be of considerable public health significance.

      Update: Enrollment into the trial was terminated by the Data and Safety Monitoring Board
      because of an imbalance in subjects with reported ARDS. At the time of termination, 42
      subjects had been enrolled. As a result, any formal evaluation of these objectives would be
      under-powered, but descriptive statistics are provided. The protocol was subsequently
      modified to protect subject safety, and the trial was re-initiated as iDEF (NCT02175225).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Number of Subjects With Modified Rankin Scale (mRS) Score 0-2
time frame: 90 days
description: The primary outcome measure of efficacy is the modified Rankin Scale (mRS) score, dichotomized to define good functional outcome as mRS 0-2 at 90 days.
The minimum mRS score is 0 (i.e. no disability). The maximum score is 6 (i.e. dead).
measure: Number of Subjects With mRS Score 0-3
time frame: 90 days
description: The proportion of DFO- and placebo-treated subjects with mRS 0-3 vs. 4-6 at 90 days
measure: Number of Subjects With Allergic/Anaphylactic Reaction
time frame: within 7 days or discharge
measure: Number of Patients With Hypotension
time frame: within 7 days or discharge
measure: Number of Patients With New Visual or Auditory Changes
time frame: within 7 days or discharge
measure: Number of Patients With Serious Adverse Events
time frame: 90 days
measure: Number of Patients Who Died During the 90-day Study Period
time frame: 90 days
description: Mortality at any time from randomization through day-90
arm group label: Deferoxamine
arm group type: Active Comparator
description: Deferoxamine mesylate supplied in vials containing 2 gm of sterile, lyophilized, powdered deferoxamine mesylate. The drug will be reconstituted for injection, by dissolving in 20 ml of sterile water. The reconstituted drug will be further diluted in normal saline to achieve a final concentration of 7.5 mg per ml.
arm group label: Normal Saline
arm group type: Placebo Comparator
description: 0.9% sodium chloride
intervention type: Drug
intervention name: Deferoxamine
description: Deferoxamine mesylate(62 mg/kg/day up to a maximum daily dose of 6000 mg/day) given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
arm group label: Deferoxamine
other name: Deferoxamine Mesylate
intervention type: Drug
intervention name: Normal saline
description: This is a placebo. Normal saline will be given by a continuous IV infusion for 5 consecutive days beginning within 24 hours of ICH symptom onset.
arm group label: Normal Saline
other name: 0.90% Sodium Chloride Solution
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Magdy Selim, MD, PhD
role: Principal Investigator
affiliation: Beth Israel Deaconess Medical Center/Harvard Medical School
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country: Canada
country: United States
citation: Selim M. Deferoxamine mesylate: a new hope for intracerebral hemorrhage: from bench to clinical trials. Stroke. 2009 Mar;40(3 Suppl):S90-1. doi: 10.1161/STROKEAHA.108.533125. Epub 2008 Dec 8.
PMID: 19064798
citation: Selim M, Yeatts S, Goldstein JN, Gomes J, Greenberg S, Morgenstern LB, Schlaug G, Torbey M, Waldman B, Xi G, Palesch Y; Deferoxamine Mesylate in Intracerebral Hemorrhage Investigators. Safety and tolerability of deferoxamine mesylate in patients with acute intracerebral hemorrhage. Stroke. 2011 Nov;42(11):3067-74. doi: 10.1161/STROKEAHA.111.617589. Epub 2011 Aug 25.
PMID: 21868742
citation: Gu Y, Hua Y, Keep RF, Morgenstern LB, Xi G. Deferoxamine reduces intracerebral hematoma-induced iron accumulation and neuronal death in piglets. Stroke. 2009 Jun;40(6):2241-3. doi: 10.1161/STROKEAHA.108.539536. Epub 2009 Apr 16.
PMID: 19372448
citation: Okauchi M, Hua Y, Keep RF, Morgenstern LB, Xi G. Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats. Stroke. 2009 May;40(5):1858-63. doi: 10.1161/STROKEAHA.108.535765. Epub 2009 Mar 12.
PMID: 19286595
responsible party type: Principal Investigator
investigator affiliation: Beth Israel Deaconess Medical Center
investigator full name: Magdy Selim
investigator title: Professor of Neurology
mesh term: Cerebral Hemorrhage
mesh term: Hemorrhage
mesh term: Deferoxamine
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limitations and caveats: The study was terminated prematurely, and only 42 subjects were enrolled. As a result, any formal evaluation of these outcomes would be under-powered. Only descriptive statistics are provided.
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