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MIS-C Comparative Effectiveness Study (MISTIC)

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ClinicalTrials.gov Identifier: NCT04898231
Recruitment Status : Recruiting
First Posted : May 24, 2021
Last Update Posted : April 6, 2022
Sponsor:
Collaborator:
Children's Hospital of Michigan
Information provided by (Responsible Party):
Adriana H. Tremoulet, University of California, San Diego

Brief Summary:
In March 2020, children exposed to the virus that causes the COVID-19 illness, SARS-CoV-2, presented with fever and significant inflammation about a month after exposure to the virus. Some children were sick enough to require care in the intensive care unit for what came to be known as Multisystem Inflammatory Syndrome-Children (MIS-C).The clinical presentation shared many features with Kawasaki disease (KD), a self-limited inflammation that can cause ballooning of the arteries of the heart. Thus, physicians reached for many of the therapies used to treat children with KD. Despite the surge of COVID-19 cases and children continuing to present with MIS-C, there are no data that guide the choice of therapy. Thus, the investigators have designed a study to determine which combination of therapies is most effective in helping children with MIS-C recover quickly.

Condition or disease Intervention/treatment Phase
Multisystem Inflammatory Syndrome-Children Drug: Infliximab Drug: Anakinra Drug: Methylprednisolone Phase 2 Phase 3

Detailed Description:
This study is a multi-site, randomized, pragmatic, comparative effectiveness study of children with MIS-C. The current standard of care is that all MIS-C patients are initially treated with IVIG and receive additional therapy if they are severely ill or do not improve clinically. This study design will randomize subjects who have received IVIG but clinically warrant further anti-inflammatory therapy to one of three treatment arms (infliximab, steroids or anakinra) and allow for re-randomization to one of the two remaining arms if clinically warranted.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This is a randomized trial of 3 treatment arms
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) Comparative Effectiveness Study
Actual Study Start Date : December 22, 2020
Estimated Primary Completion Date : December 22, 2023
Estimated Study Completion Date : December 22, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Infliximab
Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
Drug: Infliximab
Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
Other Names:
  • Remicade
  • Inflectra
  • Remsima

Active Comparator: Methylprednisilone (steroids)
Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.
Drug: Methylprednisolone
Methylprednisilone (steroids) will be administered as 2 mg/kg IV or orally divided every 12 hours. At the time of hospital discharge the patient will be given a steroid taper that will take at least 3 weeks to complete.
Other Name: Steriods

Active Comparator: Anakinra
Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.
Drug: Anakinra
Anakinra will be administered at a dose of 8 mg/kg/day IV or SQ with 100 mg every 6 hours as the max dose. This is discontinued with a taper during the hospitalization over 2-4 days once a patient is stable with significantly improved clinical course and laboratory profile.
Other Name: Kineret




Primary Outcome Measures :
  1. Anti-inflammatory treatment regimen lowest rate of second randomization [ Time Frame: 1 week ]
    To determine the anti-inflammatory treatment from first randomization that has the lowest rate of second randomization.


Secondary Outcome Measures :
  1. Anti-inflammatory treatment regimen decrease CRP from baseline [ Time Frame: 6 weeks ]
    To determine the anti-inflammatory treatment regimen that results in the most rapid reduction by 50 percent in the CRP level compared to baseline (pre-IVIG).

  2. Anti-inflammatory treatment regimen quickest return of left ventricular ejection fraction [ Time Frame: 6 weeks ]
    To determine the anti-inflammatory treatment regimen that results in the most rapid return to a sustained left ventricular ejection fraction of at least 55 percent from the start of the IVIG infusion.

  3. Anti-inflammatory treatment regimen fewest adverse events [ Time Frame: 6 weeks ]
    To determine the anti-inflammatory treatment regimen that results in the fewest serious adverse events attributed to study drug.



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 20 Years   (Child, Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. An individual aged <21 years presenting with

    1. Fever (>38.0°C for ≥24 hours; may be by subjective report) AND
    2. Two or more of the following (from two different systems; e.g. one from cardiac and one from mucocutaneous):

      Cardiac

      • Hypotension
      • Shock
      • Arrhythmia
      • Tachycardia
      • Left ventricular ejection fraction <55%
      • Valvulitis
      • Coronary artery enlargement (LAD or RCA Z-score ≥ 2.5)
      • Pericardial effusion Gastrointestinal
      • Diarrhea
      • Nausea/vomiting
      • Significant abdominal pain Immunologic
      • Lymphadenopathy (unilateral cervical or diffuse) Mucocutaneous
      • Bilateral conjunctival injection
      • Extremity swelling or erythema
      • Rash
      • Lip erythema/Strawberry tongue Neurologic
      • Altered mental status
      • Focal neurological deficits
      • Headache
      • Meningismus
    3. Laboratory evidence of inflammation, including but not limited to, an elevated C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, procalcitonin, D-dimer, ferritin, lactic acid dehydrogenase (LDH), neutrophilia, lymphopenia or hypoalbuminemia AND
    4. No alternative plausible diagnoses based on clinical judgement AND
    5. Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or suspected COVID-19 exposure AND
    6. Parent or legal guardian (or self if at least 18 years old) able and willing to provide informed consent and subject willing and able to provide assent when appropriate.

Exclusion Criteria:

  1. Known immunodeficiency
  2. Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04898231


Contacts
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Contact: Adriana Tremoulet, MD, MAS 858-246-0012 atremoulet@health.ucsd.edu

Locations
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United States, California
Rady Children's Hospital Recruiting
San Diego, California, United States, 92123
Contact: Adriana Tremoulet, MD, MAS       atremoulet@health.ucsd.edu   
United States, Michigan
Children's Hospital Michigan Recruiting
Detroit, Michigan, United States, 48201
Contact: Jocelyn Ang         
Sponsors and Collaborators
University of California, San Diego
Children's Hospital of Michigan
Investigators
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Principal Investigator: Adriana Tremoulet, MD, MAS University of California, San Diego
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Responsible Party: Adriana H. Tremoulet, Associate Director, Kawasaki Disease Research Center Professor of Pediatrics, University of California, San Diego
ClinicalTrials.gov Identifier: NCT04898231    
Other Study ID Numbers: 202109
First Posted: May 24, 2021    Key Record Dates
Last Update Posted: April 6, 2022
Last Verified: March 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Syndrome
Disease
Pathologic Processes
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Infliximab
Interleukin 1 Receptor Antagonist Protein
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Dermatologic Agents
Antirheumatic Agents