Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS
Purpose
The TRIPS study is a prospective, multi-center, double-blind, adaptively randomized, placebo-controlled clinical trial of the drug anakinra for reversal of moderate to severe hyperinflammation in children with sepsis-induced multiple organ dysfunction syndrome (MODS).
Condition
- Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
Eligibility
- Eligible Ages
- Between 1 Day and 17 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- ≥ 40 weeks corrected gestational age to < 18 years; AND - Admission to the PICU or CICU; AND - Onset of ≥ 2 new organ dysfunctions within the last 3 calendar days (compared to pre-sepsis baseline) as measured by the modified Proulx criteria; AND - Documented or suspected infection as the MODS inciting event.
Exclusion Criteria
- Weight <3kg; OR - Limitation of care order at the time of screening; OR - Patients at high likelihood of progression to brain death in opinion of the clinical team; OR - Moribund condition in which the patient is unlikely to survive the next 48 hours in opinion of the clinical team; OR - History of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia; OR - Current or prior diagnosis of hemophagocytic lymphohistiocytosis or macrophage activation syndrome; OR - Peripheral white blood cell count < 1,000 cells/mm3 as the result of myeloablative therapyOR receipt of myeloablative therapy within the previous 14 days; OR - Known allergy to anakinra, or E. coli-derived products; OR - Known pregnancy; OR - Lactating females; OR - Receipt of anakinra or GM-CSF within the previous 28 days; OR - Resolution of MODS by MODS Day 2; OR - Previous enrollment in the TRIPS study.
Study Design
- Phase
- Phase 2/Phase 3
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- Prospective, adaptively-randomized, double-blind, placebo controlled clinical trial
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Active Comparator Anakinra 4 mg/kg/day |
IV Anakinra 4mg/kg/day x 7 days |
|
|
Active Comparator Anakinra 8 mg/kg/day |
IV Anakinra 8 mg/kg/day x 7 days |
|
|
Active Comparator Anakinra 12 mg/kg/day |
IV Anakinra 12 mg/kg/day x 7 days |
|
|
Active Comparator Anakinra 16 mg/kg/day |
IV Anakinra 16 mg/kg/day x 7 days |
|
|
Placebo Comparator Placebo |
IV placebo x 7 days |
|
Recruiting Locations
Children's National and nearby locations
Washington, District of Columbia 20010
Michael Bell
More Details
- NCT ID
- NCT05267821
- Status
- Recruiting
- Sponsor
- Nationwide Children's Hospital
Detailed Description
The TRIPS study is a prospective, multi-center, double-blind, adaptively randomized, placebo-controlled clinical trial of the drug anakinra for reversal of moderate to severe hyperinflammation in children with sepsis-induced multiple organ dysfunction syndrome (MODS). Eligible subjects will undergo centralized immunophenotyping on day 2 of MODS. Subjects without immunoparalysis (a whole blood ex vivo LPS-induced TNF-alpha production capacity < 200 pg/ml) and a serum ferritin level of 500 - 2,000 ng/ml or a serum C-reactive protein (CRP) ≥ 4 mg/dl will be eligible for randomization, along with subjects with a serum ferritin level of 2,000 - 10,000 ng/ml regardless of their TNF-alpha response. Eligible subjects will receive intravenous (IV) anakinra at a dose of 4, 8, 12, or 16 mg/kg/day or placebo for 7 days.