Clinical trial NCT04898231: MIS-C Comparative Effectiveness Study
Official title: Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) Comparative Effectiveness Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE2
PHASE3
Conditions: Multisystem Inflammatory Syndrome-Children
Lead sponsor: University of California, San Diego
Sponsor class: OTHER
Collaborators: name: Children's Hospital of Michigan
First posted: 2021-05-24
Enrollment: 73
Sex: ALL
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This is a randomized trial of 3 treatment arms
Primary purpose: TREATMENT

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.

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.

Eligibility 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).

Primary outcomes:
measure: Anti-inflammatory treatment regimen lowest rate of second randomization
timeFrame: 1 week
Secondary outcomes:
measure: Anti-inflammatory treatment regimen decrease CRP from baseline
timeFrame: 6 weeks
measure: Anti-inflammatory treatment regimen quickest return of left ventricular ejection fraction
timeFrame: 6 weeks
measure: Anti-inflammatory treatment regimen fewest adverse events
timeFrame: 6 weeks
Other outcomes:
Locations:
city: San Diego
country: United States
facility: Rady Children's Hospital
state: California
city: Detroit
country: United States
facility: Children's Hospital Michigan
state: Michigan
Study officials:
affiliation: University of California, San Diego
name: Adriana Tremoulet, MD, MAS
role: PRINCIPAL_INVESTIGATOR
References: