MIS-C Comparative Effectiveness Study

Phase 2

Active, not recruiting

• Conditions: Multisystem Inflammatory Syndrome-Children
• Interventions: Drug: Methylprednisolone; Drug: Infliximab; Drug: Anakinra

• Registration Number: NCT04898231
• Lead Sponsor: 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.

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.

Study Timeline

• Study Start: 2020-12-22
• Study First Submitted: 2021-05-13
• Study First Submitted QC: 2021-05-20
• Study First Posted: 2021-05-24
• Primary Completion: 2023-12-22
• Status Verified: 2024-09
• Last Update Submitted: 2024-09-25
• Last Update Posted: 2024-09-27
• Study Completion: 2025-07-31

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 73

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).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Methylprednisilone (steroids)	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.
Infliximab	Infliximab	Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
Anakinra	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.

Primary Outcome Measures

Name	Time	Method
Anti-inflammatory treatment regimen lowest rate of second randomization	1 week	To determine the anti-inflammatory treatment from first randomization that has the lowest rate of second randomization.

Secondary Outcome Measures

Name	Time	Method
Anti-inflammatory treatment regimen quickest return of left ventricular ejection fraction	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.
Anti-inflammatory treatment regimen fewest adverse events	6 weeks	To determine the anti-inflammatory treatment regimen that results in the fewest serious adverse events attributed to study drug.
Anti-inflammatory treatment regimen decrease CRP from baseline	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).

Trial Locations

Locations (2)

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

Children's Hospital Michigan; 🇺🇸 Detroit, Michigan, United States