Pediatric Sepsis-induced MODS Clinical Trial
— GRACEOfficial title:
GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS (GRACE)
| Verified date | February 2023 |
| Source | Nationwide Children's Hospital |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
This study is an open-label, multi-center, interventional trial in which children with sepsis-induced MODS undergo surveillance immune function testing beginning on Day 2 of MODS. Those children who demonstrate immunoparalysis (TNF-alpha response <200 pg/ml) will receive a 7-day course of GM-CSF at a dose of 125 or 250 mcg/m2/day by either the intravenous (IV) or subcutaneous (SQ) route. The goal of the study is to establish the dose and route of delivery that results in resolution of immunoparalysis (TNF-alpha response >=200 pg/ml) by the morning after the 3rd scheduled dose with persistent resolution of immunoparalysis on the morning after the 7th scheduled dose. Resolution of immunoparalysis in 8 out of the first 10 subjects in a study treatment arm represents a successful dose and route. The goal of this study will be achieved through the following Specific Aims: Specific Aim 1. Establish the immunologic efficacy of GM-CSF administered by the IV and SQ routes in children with immunoparalysis in the setting of sepsis-induced MODS. Specific Aim 2. Estimate the pharmacokinetic parameters by the IV and SQ GM-CSF administered in pediatric sepsis-induced MODS. Specific Aim 3. Demonstrate the feasibility of screening, enrollment, drug delivery, and sample collection for a multi-center immunostimulation trial in children with sepsis-induced MODS.
| Status | Active, not recruiting |
| Enrollment | 120 |
| Est. completion date | December 5, 2023 |
| Est. primary completion date | December 5, 2023 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | N/A to 17 Years |
| Eligibility | Inclusion Criteria: - >= 40 weeks gestational age to <18 years; AND - Onset of >=2 new organ dysfunctions (compared to pre-sepsis baseline) as measured by the Proulx criteria; AND - Documented or suspected infection as the MODS inciting event. Exclusion Criteria: - Unable to collect a cumulative total of 20.5 mL of blood for this study due to research blood draw limits; OR - Limitation of care order at the time of screening; OR - Patients at high risk for brain death; OR - Active (or planned within 7 days) immunosuppressive treatment for oncologic, transplant, or rheumatologic disease; OR - Known primary immunodeficiency disorder; OR - Diagnosis of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia;OR - Known allergy to GM-CSF; OR - Documented hyperferritinemia (serum ferritin >= 500 ng/ml) during current sepsis event; OR - Contraindication to SQ injection (ECMO); OR - Burns where >5% of the total body surface area is affected; OR - Renal replacement therapy at the time of screening; OR - On ECMO or anticipated to require ECMO; OR - Known pregnancy; OR - Inability to collect and ship sample for immune testing on MODS Day 2; OR - Previous enrollment in the GRACE study |
| Country | Name | City | State |
|---|---|---|---|
| United States | Children's Hospital of Colorado | Aurora | Colorado |
| United States | Nationwide Children's Hospital | Columbus | Ohio |
| United States | Children's Hospital of Michigan | Detroit | Michigan |
| United States | UCLA Mattel Children's Hospital | Los Angeles | California |
| United States | Children's Hospital of Philadelphia | Philadelphia | Pennsylvania |
| United States | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
| United States | Benioff Children's Hospital/UCSF | San Francisco | California |
| United States | Children's National Medical Center | Washington | District of Columbia |
| Lead Sponsor | Collaborator |
|---|---|
| Nationwide Children's Hospital |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | TNF-alpha response | Success in a cohort is defined as improvement in the whole blood ex vivo LPS-induced TNF-alpha production capacity (TNF response) to >= 200 pg/ml by the morning after the 3rd dose and persisting to the morning after the 7th dose in at least 8 out of 10 treated subjects within a cohort | Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS |