PRISM: COVID-19: Pediatric Research Immune Network on SARS-CoV-2 and MIS-C

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Active, not recruiting

CT.gov ID

NCT04588363

Collaborator

Autoimmunity Centers of Excellence (Other), Clinical Trials in Organ Transplantation in Children (Other)

244

Enrollment

Locations

26.4

Anticipated Duration (Months)

12.2

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objectives of this study are:

To determine the proportion of children with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) related death, rehospitalization or major complications after infection with SARS-CoV-2 and/or Multisystem Inflammatory Syndrome in Children (MIS-C), and
To determine immunologic mechanisms and immune signatures associated with disease spectrum and subsequent clinical course during the year of follow-up.

Condition or Disease	Intervention/Treatment	Phase
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Multisystem Inflammatory Syndrome in Children (MIS-C) Coronavirus Disease 2019 (COVID-19)	Other: SARS-CoV-2 and/or MIS-C Exposure

Detailed Description

This is a prospective, multicenter, observational cohort study to assess short and long-term clinical outcomes and immune responses after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection and/or Multisystem Inflammatory Syndrome in Children (MIS-C) in children (e.g., defined as individuals who have not reached their 21st birthday at the time of enrollment). SARS-CoV-2 causes Coronavirus Disease 2019 (COVID-19)

Participants will be identified through active recruitment measures within hospitals and through ambulatory and laboratory-based databases of SARS-CoV-2 positive individuals <21 years of age. The study will enroll a minimum of 250 subjects from a diverse racial/ethnic background, from participating medical centers in the United States. The study period of participation is 1 year (12 months).

Study Design

Study Type:

Observational

Actual Enrollment :

244 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

An Observational Cohort Study to Determine Late Outcomes and Immunological Responses After Infection With SARS-CoV-2 in Children With and Without Multisystem Inflammatory Syndrome (MIS-C)

Actual Study Start Date :

Nov 19, 2020

Anticipated Primary Completion Date :

Aug 1, 2022

Anticipated Study Completion Date :

Feb 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
SARS-CoV-2 positive children Individuals less than 21 years of age who fulfill one or more of the following criteria: SARS-CoV-2 detection from a respiratory specimen, and/or Meets criteria for MIS-C, and/or Meets criteria for MIS-C, except has involvement of only 1 organ system	Other: SARS-CoV-2 and/or MIS-C Exposure This is an observational cohort study. Other Names: Exposure: Severe Acute Respiratory Syndrome Coronavirus 2 Infection and/or Multisystem Inflammatory Syndrome in Children diagnosis

Arm

Intervention/Treatment

SARS-CoV-2 positive children

Individuals less than 21 years of age who fulfill one or more of the following criteria: SARS-CoV-2 detection from a respiratory specimen, and/or Meets criteria for MIS-C, and/or Meets criteria for MIS-C, except has involvement of only 1 organ system

Other: SARS-CoV-2 and/or MIS-C Exposure

This is an observational cohort study.

Other Names:

Exposure: Severe Acute Respiratory Syndrome Coronavirus 2 Infection and/or Multisystem Inflammatory Syndrome in Children diagnosis

Outcome Measures

Primary Outcome Measures

Proportion of Participants With Either COVID-19-Related Death, Rehospitalization, Major Complications after SARS-CoV-2 Illness and/or MIS-C at 6 Months Post Illness Presentation [6 Months Post Illness Presentation (Enrollment)]
Participants who experience Coronavirus Disease 2019 (COVID-19)-related death, rehospitalization or major complications after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) illness and/or multisystem inflammatory syndrome in children (MIS-C).

Secondary Outcome Measures

Proportion of Participants with Coronavirus Disease 2019 (COVID-19)-Related Death after Multisystem Inflammatory Syndrome in Children (MIS-C) at 1 Year Post Illness Presentation [1 Year Post Illness Presentation (Enrollment)]
Participants who experience Coronavirus Disease 2019 (COVID-19)-related death, rehospitalization or major complications after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) illness and/or multisystem inflammatory syndrome in children (MIS-C).
All-Cause Mortality [1 Year Post Illness Presentation (Enrollment)]
The occurrence of death in participants regardless of relationship to Coronavirus Disease 2019 (COVID-19) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2).
Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Mortality [1 Year Post Illness Presentation (Enrollment)]
The occurrence of SARS-CoV-2 related death in participants.
Hospitalization for Participants Enrolled as an Outpatient or Rehospitalization after First Admission in Hospitalized Participants [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of Participants who require: Hospitalization subsequent to enrollment as an outpatient for SARS-CoV-2/COVID-19 related illness and/or MIS-C, or Rehospitalization after discharge from their initial admission for SARS-CoV-2/COVID-19 related illness and/or MIS-C. Abbreviations: Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Coronavirus Disease 2019 (COVID-19) Multisystem Inflammatory Syndrome in Children (MIS-C)
Coagulation Abnormality by D-Dimer Biomarker [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of dysregulation involving the coagulation system by D-dimer laboratory test.
Coagulation Abnormality by Fibrinogen Biomarker [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of dysregulation involving the coagulation system by fibrinogen laboratory test.
Coagulation Abnormality by Prothrombin Time (PT) and Activated Partial Thromboplastin Time (PTT) Biomarkers [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of dysregulation involving the coagulation system by PT and PTT laboratory tests.
Coagulation Abnormality by International Normalised Ratio (INR) Biomarker [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of dysregulation involving the coagulation system by INR laboratory test.
Coronary Artery Abnormalities [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of coronary artery abnormalities (e.g., by echocardiogram and, if performed for clinical indications, angiogram, as examples).
Pulmonary Hypertension [Up to 1 Year Post Illness Presentation (Enrollment)]
Prevalence of pulmonary hypertension by echocardiogram and standard of care assessments.
Cardiovascular System Dysregulation by B-type natriuretic peptide (BNP) Biomarker [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of cardiovascular system dysregulation by BNP laboratory test.
Cardiovascular System Dysregulation by Troponin I Biomarker [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of cardiovascular system dysregulation by Troponin I laboratory test.
Cardiovascular System Dysregulation by Echocardiogram [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of cardiac function by echocardiogram (Echo), a test that uses high frequency sound waves (ultrasound) to make pictures of the heart. The test is also referred to as a diagnostic cardiac ultrasound.
Cardiovascular System Dysregulation by Electrocardiogram (ECG) [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of cardiovascular system dysregulation(s) evaluated by standardized 12-lead electrocardiogram. ECG rhythms, intervals and voltages will be assessed. Cross reference: ECG and EKG are used interchangeably.
Pulmonary Abnormalities [Up to 1 Year Post Illness Presentation (Enrollment)]
Pulmonary fibrosis (i.e., scarring) or other abnormalities detected by computerized tomography (CT) imaging.
Pulmonary Function Characteristics [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization by pulmonary function tests (spirometry without bronchodilators).
Renal/Metabolic Biomarkers: Serum Creatinine and Blood Urea Nitrogen (BUN) [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of kidney/metabolic function by serum creatinine and blood urea nitrogen (BUN) laboratory tests
Renal/Metabolic Biomarker: Estimated glomerular filtration rate (eGFR) [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of kidney/metabolic function by the estimated glomerular filtration rate (eGFR) calculated value, using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation.
Hepatic/Metabolic Biomarkers: Serum Alkaline Phosphatase (Alk Phos), Alanine Aminotransferase ( ALT/SGPT)and Aspartate Aminotransferase (AST/SGOT) [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of liver/metabolic function by the following laboratory tests: alkaline phosphatase alanine aminotransferase (ALT/SGPT) and aspartate aminotransferase (AST/SGOT).
Hepatic/Metabolic Biomarker: Total Bilirubin [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of liver/metabolic function by serum total bilirubin laboratory test.
Neurologic Abnormalities [Up to 1 Year Post Illness Presentation (Enrollment)]
Characterization of neurologic sequelae of infection/disease.
Other End Organ and/or functional abnormalities Occurring After Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection/ Coronavirus Disease 2019 (COVID-19) and/or Multisystem Inflammatory Syndrome in Children (MIS-C) [Up to 1 Year Post Illness Presentation (Enrollment)]
Identified by and characterized during standard of care assessments.
Health Related Quality of Life [Up to 1 Year Post Illness Presentation (Enrollment)]
Assessment of health-related quality of life (HRQOL) after Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection/ Coronavirus Disease 2019 (COVID-19) and/or multisystem inflammatory syndrome in children (MIS-C). The Pediatric Quality of Life Inventory is a series of assessment instruments designed to measure the health-related quality of life of children. The PedsQL 4.0 provides an opportunity for the assessment of both overall (generic) quality of life as well as disease-specific quality of life. The PedsQL 4.0 Generic Core Scales are appropriate for assessing health-related quality of life in both healthy and chronically ill children. The four scales making up this generic battery include Physical Functioning (8 items), Emotional Functioning (5 items), Social Functioning (5 items), and School Functioning (5 items).

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 20 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) detection from a respiratory specimen, and/or
Meets criteria for Multisystem Inflammatory Syndrome in Children (MIS-C), and/or
Meets criteria for MIS-C, except has involvement of only 1 organ system

Cases meeting clinical criteria for MIS-C but without known SARS-CoV-2 exposure, and who are being treated as MIS-C by the treating physician, but with negative SARS-CoV-2 PCR and pending or negative antibody testing, may be enrolled as subjects. If subsequent antibody testing is positive, cases will be labelled as confirmed MIS-C. If SARS-CoV-2 antibody testing is negative, subjects will be labeled at the end of the study as suspected/not confirmed MIS-C.

Exclusion Criteria:

Subject and/or parent/guardian who are not able to understand or be willing to provide informed consent and where applicable assent

--Note, for this observational cohort study, participation in other COVID-19 studies is not an automatic exclusionary criterion.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Loma Linda University Health	Loma Linda	California	United States	92354
2	Cedars-Sinai Medical Center	Los Angeles	California	United States	90048
3	Children's Hospital Los Angeles	Los Angeles	California	United States	91011
4	Lucile Packard Children's Hospital Stanford	Palo Alto	California	United States	94303
5	Children's Healthcare of Atlanta	Atlanta	Georgia	United States	30322
6	Mayo Clinic Rochester	Rochester	Minnesota	United States	55905
7	St. Louis Children's Hospital	Saint Louis	Missouri	United States	63110
8	Children's Hospital at Montefiore	Bronx	New York	United States	10467
9	NewYork-Presbyterian Brooklyn Methodist Hospital	Brooklyn	New York	United States	11215
10	NewYork-Presbyterian Queens Hospital	Flushing	New York	United States	11355
11	Cohen Children's Medical Center - Northwell Health	New Hyde Park	New York	United States	11040
12	Hassenfeld Children's Hospital at NYU Langone	New York	New York	United States	10016
13	NewYork-Presbyterian Komansky Children's Hospital	New York	New York	United States	10021
14	Mount Sinai Kravis Children's Hospital	New York	New York	United States	10029
15	Duke University Children's Health Center	Durham	North Carolina	United States	27710
16	Cincinnati Children's Hospital Medical Center	Cincinnati	Ohio	United States	45229
17	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
18	UPMC Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
19	Medical University of South Carolina, Pediatric Rheumatology	Charleston	South Carolina	United States	29425
20	Monroe Carell Jr. Children's Hospital at Vanderbilt	Nashville	Tennessee	United States	37232

Sponsors and Collaborators

National Institute of Allergy and Infectious Diseases (NIAID)
Autoimmunity Centers of Excellence
Clinical Trials in Organ Transplantation in Children

Investigators

Study Chair: Steven A. Webber, MBChB, MRCP, Department of Pediatrics, Monroe Carell Jr. Children's Hospital at Vanderbilt
Principal Investigator: James D. Wilkinson, MD, MPH, Vanderbilt Institute for Clinical and Translational Research (VICTR)
Principal Investigator: Natasha B Halasa, MD, MPH, Department of Pediatrics, Vanderbilt University Medical Center
Principal Investigator: Virginia Pascual, MD, Gale and Ira Drukier Institute for Children's Health, Weill Cornell Medicine
Principal Investigator: Betty Diamond, MD, Institute of Molecular Medicine, The Feinstein Institute for Medical Research
Principal Investigator: Ignacio Sanz, MD, Division of Rheumatology, Emory University
Principal Investigator: Olivia Martinez, PhD, Stanford University
Principal Investigator: Sheri Krams, PhD, Stanford University
Principal Investigator: Jeremy Boss, PhD, Emory University