Convalescent Plasma in Pediatric COVID-19

Study Overview
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Brief Summary
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COVID-19 is increasingly affecting children but convalescent plasma (CP) has not been adequately studied in children to date. The study will determine safety of convalescent plasma for pediatric patients with severe, or at high risk for severe, COVID-19 disease.

Detailed Description
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COVID19 is an emerging infection with no current approved treatment or prevention. COVID-19 is increasingly affecting children but convalescent plasma (CP) has not been adequately studied in children to date. The study will determine safety of convalescent plasma for pediatric patients with severe, or at high risk for severe, COVID-19 disease.

Official Title
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Convalescent Plasma to Optimize Treatment of COVID-19 Disease in Pediatric Patients: A Feasibility Study

Conditions
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COVID

Intervention / Treatment
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* Biological: Convalescent Plasma (CP)
* Drug: Standard COVID-19 therapies


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 0 to 22 years of age SARS-CoV-2 infection documented by RNA RT-PCR detection Admitted to an acute care facility Ability of patient or guardian to provide consent and assent (if applicable); if patient is intubated assent may be waived Exclusion Criteria: Pregnancy/ breast feeding Medical condition that increases the risk of plasma infusion Contraindication to transfusion (severe volume overload, history of anaphylaxis to blood products). Inclusion criteria for infusion: Severe COVID-19 disease, OR Moderate disease with a risk of progression to severe or life threatening disease, OR Severely immunocompromised patient with any illness attributed to COVID-19 disease requiring inpatient care. Exclusion to infusion: Pregnancy/ breast feeding Medical condition that increases the risk of plasma infusion Contraindication to transfusion (severe volume overload, history of anaphylaxis to blood products).

Ages Eligible for Study
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Minimum Age: 0 Years
Maximum Age: 22 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Convalescent Plasma (CP)<br>Once the patient meets criteria for CP infusion (severity of disease and risk factor determination and absence of exclusion criteria) convalescent plasma will be administered | Biological: Convalescent Plasma (CP)<br>* Once the patient meets criteria for CP infusion (severity of disease and risk factor determination and absence of exclusion criteria), an ABO compatible product will be identified. The CP dose administered will be 10mL/kg/dose (up to 2 units per dose) times two doses per patient for a total dose of 20 mL/kg. Patients will be followed for adverse events and clinical response. Research blood testing will be obtained prior to infusion (baseline) and serially weekly afterwards until clinical resolution. Patients will receive 2 doses equaling 20 mL/kg (if available) of ABO compatible CP over 24-48 hours if they do not experience grade 3-5 adverse events that are possible, probably, or definitely attributed to CP after the first dose. Patients will be followed for adverse events for a minimum of 28 days after the last infusion of CP.<br>Drug: Standard COVID-19 therapies<br>* If clinical status permits, administration of additional COVID-19 therapies should be delayed 48 hours or more from CP infusion completion. Supportive care will be administered by best clinical practice.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of grade 3-5 adverse events that are possible, probably or definitely related to the convalescent plasma (CP) infusion | Safety of convalescent plasma for pediatric patients will be determined by capturing the grade 3-5 adverse events that are possible, probably or definitely related to the CP infusion, defined using the NCI Common Terminology Criteria for Adverse Events (CTCAE) | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in percent of supplemental oxygen | Change in percent of supplemental oxygen within 72 hours after infusion | Baseline, 72 hours after infusion | 
| Number of patients that required change in level of respiratory support | Number of patients that required change in level of respiratory support such as nasal canula, non-invasive ventilation, mechanical ventilation, high frequency oscillator ventilation, and extracorporeal membrane oxygenation (ECMO) | Baseline, 72 hours after infusion | 
| Mortality | Number of deaths | up to 1 year | 
| Mean length of ICU stay (days) | Length of ICU stay (days) will be recorded | Up to 28 days | 
| Mean length of hospital stay (days) | Length of hospital stay (days) will be recorded | Up to 28 days | 
| Mean length of ventilation (days) | Length of ventilation (days) will be recorded | Up to 28 days | 
| Number of patients with progression to renal dysfunction and/or multisystem organ failure | Number of patients with progression to renal dysfunction and/or multisystem organ failure will be recorded | up to 1 year | 
| IL-6 level | Cytokine milieu will be assayed by Luminex | up to 28 days | 
| Number of anti-SARS CoV 2 specific T cells | Cellular studies will be used for evaluation of anti-SARS CoV 2 specific T cells | up to 28 days | 
| Diversity of circulating T cells | Cellular studies will be used for evaluation of diversity of circulating T cells | up to 28 days | 
| ARS-CoV-2 Antibody Titer | Antibody titers to SARS-CoV-2 evaluation will be performed in vivo | up to 28 days | 
| SARS-CoV-2 Neutralizing Titer | Neutralizing antibodies are a type of virus specific antibody that not only bind virus but bind in a manner that prevents viral infection. Test will be will be performed in vivo. | up to 28 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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COVID-19, Pediatric, Convalescent Plasma, Safety