Multisystem Inflammatory Syndrome-ChildrenPhase 2/3MISTICNCT04898231
MIS-C Comparative Effectiveness Study
A Phase 2/3 study testing Infliximab, Anakinra and Methylprednisolone in people with Multisystem Inflammatory Syndrome-Children, run by University of California, San Diego at 2 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 20 years
- Conditions the study is for
- Multisystem Inflammatory Syndrome-Children
- What is being tested?
- Infliximab, Anakinra and Methylprednisolone
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 73 participants
- Where
- 2 sitesUnited States
- Study dates
- 22 Dec 2020to 25 Apr 2024
- Phase
- Phase 2/3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 20 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- An individual aged <21 years presenting with
- Fever (>38.0°C for ≥24 hours; may be by subjective report) AND
- Two or more of the following (from two different systems; e.g. one from cardiac and one from mucocutaneous):
- Cardiac
- Hypotension
- Shock
Show all 28Show fewer
- 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
- 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
- No alternative plausible diagnoses based on clinical judgement AND
- Positive for current or recent SARS-CoV-2 infection by RT-PCR, serology, or antigen test; or suspected COVID-19 exposure AND
- 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.
Who cannot join
- Known immunodeficiency
- Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Children's Hospital Michigan
Detroit, Michigan, 48201
Rady Children's Hospital
San Diego, California, 92123
About this study
Official title: Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) Comparative Effectiveness Study
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.
Read the 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.
- Being tested
- Infliximab, Anakinra, Methylprednisolone
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
InfliximabDrug
Also called Remicade, Inflectra, Remsima
Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours.
AnakinraDrug
Also called Kineret
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.
Also called Steriods
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.
| Study group | Role | What they receive |
|---|---|---|
| Infliximab | Active comparator | Infliximab will be administered as a single IV dose of 10 mg/kg over 2 hours. Receives: Drug: Infliximab |
| Methylprednisilone (steroids) | Active comparator | 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. Receives: Drug: Methylprednisolone |
| Anakinra | Active comparator | 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. Receives: Drug: Anakinra |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Needing Additional Anti-inflammatory Therapy Within the First Week of First Randomization
The three arms of the study will be compared to see which initial randomization arm (infliximab, anakinra or steroids) has the lowest rate of additional anti-inflammatory therapy within the first week of first randomization.
Measured: 1 week
Secondary outcomes (1)
Number of Participants With Adverse Events
Of the three initial randomization arms (infliximab, steroids or anakinra), the rate of adverse events will be compared. The goal is to determine which arm has the lowest rate of adverse events. The AEs reported in the AE section include: All Cause, SAE and Others.
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 May 2021
- Study start22 Dec 2020
- Primary completion22 Dec 2023
- Study completion25 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Multisystem Inflammatory Syndrome-ChildrenStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomized trial of 3 treatment arms
- Masking
- None (open label)
- Enrolment
- 73 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of California, San Diego
- Sponsor type
- University, hospital or other
- Collaborators
- Children's Hospital of Michigan
- Responsible party
- Principal investigator, Adriana H. Tremoulet, University of California, San Diego
- Investigators
- Adriana Tremoulet, MD, MAS, Principal investigator, University of California, San Diego
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04898231
- Sponsor's protocol ID
- 202109
- Acronym
- MISTIC
- Status last verified
- Oct 2025
- First submitted
- 13 May 2021
- Last updated
- 4 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Jain S, He F, Cheng Y, Ang JY, Burns JC, Tremoulet AH. Multisystem Inflammatory Syndrome Therapies in Children: A Comparative Effectiveness Trial. J Pediatr. 2026 Aug 19;299:115293. doi: 10.1016/j.jpeds.2026.115293. Online ahead of print.
PubMed 42617793Jain 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.
PubMed 36694613
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Multisystem Inflammatory Syndrome Therapies in Children (MISTIC) Comparative Effectiveness Study
- ClinicalTrials.gov ID
- NCT04898231
- Acronym / sponsor ID
- MISTIC / 202109
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 73 participants (actual)
- Lead sponsor
- University of California, San DiegoUniversity, hospital or other
- Collaborators
- Children's Hospital of Michigan
- Study start
- 22 Dec 2020 (actual)
- Primary completion
- 22 Dec 2023 (actual)
- Study completion
- 25 Apr 2024 (actual)
- First posted
- 24 May 2021 (actual)
- Results
- Posted 4 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
- Model description
- This is a randomized trial of 3 treatment arms
| Arm | Type | Receives |
|---|---|---|
| Infliximab | Active comparator | Drug: InfliximabInfliximab will be administered as a single IV dose of 10 mg/kg over 2 hours. |
| Methylprednisilone (steroids) | Active comparator | Drug: MethylprednisoloneMethylprednisilone (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. |
| Anakinra | Active comparator | Drug: AnakinraAnakinra 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. |
Who may qualify
- Ages
- Up to 20 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (28 listed)
- An individual aged <21 years presenting with
- Cardiac
Key exclusion criteria (2 listed)
- Known immunodeficiency
- Pre-existing medical condition that precludes receiving one or more of the study medications (e.g. TB, drug allergy to study medication).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| InfliximabAlso: Remicade, Inflectra, RemsimaInfliximab will be administered as a single IV dose of 10 mg/kg over 2 hours. | Drug | Infliximab |
| AnakinraAlso: KineretAnakinra 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 |
| MethylprednisoloneAlso: SteriodsMethylprednisilone (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 | Methylprednisilone (steroids) |
Primary outcome
Number of Participants Needing Additional Anti-inflammatory Therapy Within the First Week of First Randomization
Time frame: 1 week
The three arms of the study will be compared to see which initial randomization arm (infliximab, anakinra or steroids) has the lowest rate of additional anti-inflammatory therapy within the first week of first randomization.
1 secondary outcome
Number of Participants With Adverse Events
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 42617793Jain S, He F, Cheng Y, Ang JY, Burns JC, Tremoulet AH. Multisystem Inflammatory Syndrome Therapies in Children: A Comparative Effectiveness Trial. J Pediatr. 2026 Aug 19;299:115293. doi: 10.1016/j.jpeds.2026.115293. Online ahead of print.
- Derived from this study: PubMed 36694613Jain 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.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Adriana Tremoulet, MD, MAS principal investigator
University of California, San Diego
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Infliximab, Anakinra and Methylprednisolone in people with Multisystem Inflammatory Syndrome-Children, run by University of California, San Diego at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 28 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 4 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 4 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Needing Additional Anti-inflammatory Therapy Within the First Week of First Randomization (time frame: 1 week). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04898231, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Nov 2025.