MIS-C Comparative Effectiveness Study

NCT ID: NCT04898231

Last Updated: 2025-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 73 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-22
• Study Completion Date: 2024-04-25

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.

Conditions

Multisystem Inflammatory Syndrome-Children

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Anakinra

Intervention Type: DRUG

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.

Infliximab

Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.

Group Type: ACTIVE_COMPARATOR

Infliximab

Intervention Type: DRUG

Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.

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.

Group Type: ACTIVE_COMPARATOR

Methylprednisolone

Intervention Type: DRUG

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.

Interventions

Infliximab

Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Remicade; Inflectra; Remsima; Kineret; Steriods

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).

• Maximum Eligible Age: 20 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's Hospital of Michigan

OTHER

Sponsor Role: collaborator

University of California, San Diego

OTHER

Sponsor Role: lead

Responsible Party

Adriana H. Tremoulet

Associate Director, Kawasaki Disease Research Center Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Adriana Tremoulet, MD, MAS

Role: PRINCIPAL_INVESTIGATOR

University of California, San Diego

Locations

Rady Children's Hospital

San Diego, California, United States

Children's Hospital Michigan

Detroit, Michigan, United States

Countries

United States

References

Jain S, He F, Brown K, Burns JC, Tremoulet AH. Multisystem Inflammatory Syndrome therapies in children (MISTIC): A randomized trial. Contemp Clin Trials Commun. 2023 Apr;32:101060. doi: 10.1016/j.conctc.2023.101060. Epub 2023 Jan 20.

Reference Type: DERIVED

PMID: 36694613 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

202109

Identifier Type: -

Identifier Source: org_study_id