<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/NCT03237819</url>
  </required_header>
  <id_info>
    <org_study_id>AOR16028</org_study_id>
    <nct_id>NCT03237819</nct_id>
  </id_info>
  <brief_title>Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care</brief_title>
  <acronym>MAGMAT</acronym>
  <official_title>Interest of Magnesium Sulfate in Thrombotic Thrombocytopenic Purpura in Intensive Care: Multicentric Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Assistance Publique - Hôpitaux de Paris</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Assistance Publique - Hôpitaux de Paris</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Thrombotic Thrombocytopenic Purpura (TTP) is a potentially life-threatening thrombotic&#xD;
      microangiopathy caused by a severe deficiency of ADAMTS13 (a disintegrin and&#xD;
      metalloproteinase with a thrombospondin type 1 motif member 13). Decreased ADAMTS13 activity&#xD;
      leads to an accumulation of ultralarge von Willebrand factor (vWF) multimers which induce&#xD;
      aggregation of platelets and microthrombi. These microthrombi may involve the brain, heart,&#xD;
      kidneys and lead to life-threatening organ failures.&#xD;
&#xD;
      In experimental models, magnesium sulfate increases cleavage of newly released vWF by&#xD;
      ADAMTS13, decreases the endothelial secretion of ultralarge vWF and inhibits the interaction&#xD;
      of vWF with platelets. In another thrombotic microangiopathy, magnesium sulfate has been&#xD;
      shown to reduce the risk of seizures in women with severe pre-eclampsia. In analogy with its&#xD;
      evidence-based therapeutic application in pre-eclampsia and based on a strong rationale for&#xD;
      magnesium supplementation in TTP, we propose a phase 3, double blind, placebo controlled, and&#xD;
      randomized study to evaluate the efficacy of magnesium sulfate in more rapidly restoring&#xD;
      normal platelet counts as measure of prevention of further microvascular thrombosis in&#xD;
      patients with Thrombotic Thrombocytopenic Purpura.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date type="Actual">May 27, 2018</start_date>
  <completion_date type="Anticipated">December 1, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <intervention_model_description>multicentre double-blind randomized clinical trial</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
    <masking_description>For each day of treatment, 4 ampoules of 10 ml will be distributed to the patient's nurse (4 ampoules of 1.5g of magnesium sulphate or 3 ampoules of 5% glucose as placebo).&#xD;
The bulbs will be labeled identically so that the blind can be maintained Moreover, in order to preserve the blind, the dosage of magnesemia should not be performed outside of a necessity judged by the clinician in charge of the patient</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Time to normalization of the platelet count</measure>
    <time_frame>3 months</time_frame>
    <description>Normalization of the platelet is defined as a platelet count that reaches at least 150,000 per cubic millimeter for 48 consecutive hours</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Duration and volume of plasma exchanges</measure>
    <time_frame>30 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>platelet count</measure>
    <time_frame>5 days</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>proportion of subjects with refractory TTP</measure>
    <time_frame>5 days</time_frame>
    <description>absence of platelet count doubling after 4 days of standard treatment</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with an exacerbation of TTP</measure>
    <time_frame>30 days</time_frame>
    <description>recurrence during the 30 days after the last daily plasma exchange</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of subjects with a relapse of TTP</measure>
    <time_frame>3 months</time_frame>
    <description>recurrence occurring more than 30 days after the last daily plasma exchange</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cardiac trouble frequency</measure>
    <time_frame>day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cerebral trouble frequency</measure>
    <time_frame>day 30</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Acute kidney injury</measure>
    <time_frame>day 30</time_frame>
    <description>Kidney Disease: Improving Global Outcomes (KDIGO) score &gt; or = 1</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to normalization of hemolysis marker levels</measure>
    <time_frame>day 30</time_frame>
    <description>Lactate dehydrogenase (LDH), haptoglobin, bilirubinemia, hemoglobin</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital length of stay</measure>
    <time_frame>day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Hospital mortality</measure>
    <time_frame>day 90</time_frame>
    <description>90 days after randomization</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU length of stay</measure>
    <time_frame>day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ICU mortality</measure>
    <time_frame>day 90</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adverse events related to the use of magnesium sulfate</measure>
    <time_frame>day 7</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">74</enrollment>
  <condition>Thrombotic Thrombocytopenic Purpura</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Glucose serum (3 ampoules)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Magnesium Sulfate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>20/5000 magnesium sulfate (4 ampoules, 1,5g each)</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sulfate, Magnesium</intervention_name>
    <description>Magnesium sulphate will be administered at a dose of 6g over 20 min intravenously followed by a continuous infusion of 6g / 24h for 3 days.&#xD;
For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of 1,5g of magnesium sulfate)</description>
    <arm_group_label>Magnesium Sulfate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo - Concentrate</intervention_name>
    <description>For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of glucose 5% as placebo)</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age &gt; or = 18 years&#xD;
&#xD;
          -  Health insurance&#xD;
&#xD;
          -  Signed inform consent by patient or relatives&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  No health insurance&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Saint Louis hospital</name>
      <address>
        <city>Paris</city>
        <zip>75010</zip>
        <country>France</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>France</country>
  </location_countries>
  <verification_date>June 2021</verification_date>
  <study_first_submitted>June 13, 2017</study_first_submitted>
  <study_first_submitted_qc>July 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2017</study_first_posted>
  <last_update_submitted>October 28, 2021</last_update_submitted>
  <last_update_submitted_qc>October 28, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Thrombotic Thrombocytopenic Purpura</keyword>
  <keyword>Intensive care</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Purpura</mesh_term>
    <mesh_term>Purpura, Thrombocytopenic</mesh_term>
    <mesh_term>Purpura, Thrombotic Thrombocytopenic</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Magnesium Sulfate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03237819
org study id: AOR16028
nct id: NCT03237819
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Thrombotic Thrombocytopenic Purpura (TTP) is a potentially life-threatening thrombotic
      microangiopathy caused by a severe deficiency of ADAMTS13 (a disintegrin and
      metalloproteinase with a thrombospondin type 1 motif member 13). Decreased ADAMTS13 activity
      leads to an accumulation of ultralarge von Willebrand factor (vWF) multimers which induce
      aggregation of platelets and microthrombi. These microthrombi may involve the brain, heart,
      kidneys and lead to life-threatening organ failures.

      In experimental models, magnesium sulfate increases cleavage of newly released vWF by
      ADAMTS13, decreases the endothelial secretion of ultralarge vWF and inhibits the interaction
      of vWF with platelets. In another thrombotic microangiopathy, magnesium sulfate has been
      shown to reduce the risk of seizures in women with severe pre-eclampsia. In analogy with its
      evidence-based therapeutic application in pre-eclampsia and based on a strong rationale for
      magnesium supplementation in TTP, we propose a phase 3, double blind, placebo controlled, and
      randomized study to evaluate the efficacy of magnesium sulfate in more rapidly restoring
      normal platelet counts as measure of prevention of further microvascular thrombosis in
      patients with Thrombotic Thrombocytopenic Purpura.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: multicentre double-blind randomized clinical trial
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
masking description: For each day of treatment, 4 ampoules of 10 ml will be distributed to the patient's nurse (4 ampoules of 1.5g of magnesium sulphate or 3 ampoules of 5% glucose as placebo).
The bulbs will be labeled identically so that the blind can be maintained Moreover, in order to preserve the blind, the dosage of magnesemia should not be performed outside of a necessity judged by the clinician in charge of the patient
measure: Time to normalization of the platelet count
time frame: 3 months
description: Normalization of the platelet is defined as a platelet count that reaches at least 150,000 per cubic millimeter for 48 consecutive hours
measure: Duration and volume of plasma exchanges
time frame: 30 days
measure: platelet count
time frame: 5 days
measure: proportion of subjects with refractory TTP
time frame: 5 days
description: absence of platelet count doubling after 4 days of standard treatment
measure: Proportion of subjects with an exacerbation of TTP
time frame: 30 days
description: recurrence during the 30 days after the last daily plasma exchange
measure: Proportion of subjects with a relapse of TTP
time frame: 3 months
description: recurrence occurring more than 30 days after the last daily plasma exchange
measure: Cardiac trouble frequency
time frame: day 30
measure: Cerebral trouble frequency
time frame: day 30
measure: Acute kidney injury
time frame: day 30
description: Kidney Disease: Improving Global Outcomes (KDIGO) score > or = 1
measure: Time to normalization of hemolysis marker levels
time frame: day 30
description: Lactate dehydrogenase (LDH), haptoglobin, bilirubinemia, hemoglobin
measure: Hospital length of stay
time frame: day 90
measure: Hospital mortality
time frame: day 90
description: 90 days after randomization
measure: ICU length of stay
time frame: day 90
measure: ICU mortality
time frame: day 90
measure: Adverse events related to the use of magnesium sulfate
time frame: day 7
arm group label: Placebo
arm group type: Placebo Comparator
description: Glucose serum (3 ampoules)
arm group label: Magnesium Sulfate
arm group type: Experimental
description: 20/5000 magnesium sulfate (4 ampoules, 1,5g each)
intervention type: Drug
intervention name: Sulfate, Magnesium
description: Magnesium sulphate will be administered at a dose of 6g over 20 min intravenously followed by a continuous infusion of 6g / 24h for 3 days.
For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of 1,5g of magnesium sulfate)
arm group label: Magnesium Sulfate
intervention type: Drug
intervention name: Placebo - Concentrate
description: For each day of treatment, 4 ampoules of 10 ml will be distributed to the nurse in charge of the patient (4 ampoules of glucose 5% as placebo)
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: France
responsible party type: Sponsor
mesh term: Purpura
mesh term: Purpura, Thrombocytopenic
mesh term: Purpura, Thrombotic Thrombocytopenic
mesh term: Magnesium Sulfate
sharing ipd: Undecided