Covid-19 Infection, Hospitalized Children
Conditions
Keywords
covid-19, hospitalized children, convalescent plasma therapy
Brief summary
This is a multicentered, open-label, randomized controlled Phase 2 trial to evaluate the safety and efficacy of providing human coronavirus-immune convalescent plasma as treatment for COVID-19 disease in hospitalized children in the context of the COVID-19 pandemic.
Detailed description
SARS-CoV-2 viral infection resulting in COVID-19 disease has recently been designated by the World Health Organization as a global pandemic. Outbreak forecasting and mathematical models suggest that the number of COVID-19 cases will continue to rise over the coming weeks and months. There is an urgent public health need for rapid development of novel interventions. This protocol aims to use passive antibody therapy via convalescent plasma from SARS-CoV-2-infected patients who have developed antibody immunity, COVID-19 convalescent plasma (C19-CP), as treatment for hospitalized children with COVID-19 disease at pediatric academic hospitals across Canada. The unknown role for convalescent plasma in treating COVID-19 necessitates further study.
Interventions
BIOLOGICALConvalescent plasma (CP)
Participants will receive one infusion of convalescent plasma proportional to their weight (10 mL/kg), up to a maximum of 500 mL
Sponsors
C17 Council (regulatory sponsor)
The Hospital for Sick Children
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will be randomized to receive either standard of care (SoC) products (control) or COVID-19 convalescent plasma (C19-CP) plus standard of care while being hospitalized for COVID-19 (ratio 1:2). The intervention will consist of a single transfusion of convalescent plasma.
Eligibility
Sex/Gender
ALL
Age
No minimum to 18 Years
Healthy volunteers
No
Inclusion criteria
1. Age 0 to \<19 years old 2. Hospitalized with symptoms compatible with COVID-19 illness 3. Laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen prior to randomization. 4. ABO compatible convalescent plasma available
Exclusion criteria
1. Onset of symptoms began \>12 days before screening 2. History of adverse reactions to blood products or other contraindication to transfusion 3. Refusal of plasma for religious or other reasons 4. Acute heart failure with fluid overload 5. Any condition or diagnosis, that could in the opinion of the Site Principal Investigator interfere with the participant's ability to comply with study instructions, or put the participant at risk 6. Anticipated discharge within 24 hours Note: The intent of this
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical recovery | at day 30 | defined in the last 24 hours as normal respiratory and heart rate (or return to baseline, absence of fever, absence of low blood pressure, oxygen saturation greater than 94% or room air (or return to baseline), no need for intravenous fluids (or return to baseline) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| respiratory status -4 | from admission to day 30 of hospitalization | Mean number of ventilator days in 30 days |
| Mortality 1b | at 90 days | Time to in-hospital death censored |
| Mortality 2a | at 30 days | Proportion of patients with Survival status |
| Mortality 2b | at 90 days | Proportion of patients with Survival status |
| Care and Critical Care | at 30 days | Length of hospitalization and stay in the ICU |
| organ systems: renal | up to 365 days | The proportion of patients needing renal replacement therapy |
| organ systems: cardiac | up to 365 days | The proportion of patients developing myocarditis |
| Transfusion-associated adverse events (AE) | up to 365 days | The proportion of patients developing adverse events to the treatment arm, C19-CP as assessed by Proposed Standard definitions for surveillance of non-infectious adverse transfusion reactions. |
| Safety of the intervention | up to 365 days | cumulative incidence of severe and life-threatening AEs and severe AEs |
| organ systems: multi-system inflammatory disease | up to 365 days | The proportion of patients developing multi-system inflammatory disease |
| Combined mortality/intubation | at 30 day | Proportion of patients experiencing death in hospital (Yes/No) 30 days |
| Respiratory status-1 | at 30 days | Proportion of patients experiencing Intubation (Yes/No) |
| Respiratory status-2 | time from admission to intubation | time to intubation |
| Respiratory status-3 | from admission to day 30 of hospitalization | Mean number of ventilator-free days in 30 days |
| respiratory status -5 | from admission to day 30 of hospitalization | The number of oxygen free days in the first 30 days or the incidence and duration of new oxygen use during the trial, defined as oxygen use that was not present at time of randomization but occurs subsequently |
| respiratory status-6 | at 30 days | The proportion of patients needing ECMO in 30 days |
| Mortality 1a | at 30 days | Time to in-hospital death censored |
Other
| Measure | Time frame | Description |
|---|---|---|
| Virological measures 4 | at day 15 | Proportion of patients with negative virology |
| Modulation of biomarkers | up to 365 days | Exploratory analysis of biomarker differences between groups |
| Resolution of fever | hours | Time to fever resolution (no longer requiring fever management) |
| Presence and titres levels | at day 30 | Presence and titres of IgG, IgA antibodies and neutralizing antibody titres in C19-CP group on the primary outcome and other outcomes. |
| Functional measure 1 | up to 365 days | efficacy of C19-CP on respiratory measures using pediatric validated dyspnea (breathlessness) scales |
| Functional measure 2 | up to 365 days | Evaluate the efficacy of C19-CP on quality of life (QOL) measures using Validated QOL scores (Eq-5D) |
| Functional measure 3 | up to 365 days | Evaluate the efficacy of C19-CP on rehospitalization after discharge |
| Virological measures 1 | at day 3 | Proportion of patients with negative virology |
| Virological measures 3 | at day 10 | Proportion of patients with negative virology |
Countries
Canada
Outcome results
None listed