Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS
- Conditions
- Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
- Interventions
- Drug: Placebo
- Registration Number
- NCT05267821
- Lead Sponsor
- Nationwide Children's Hospital
- Brief Summary
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).
- 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.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 500
- ≥ 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.
- 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
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo IV placebo x 7 days Anakinra 4 mg/kg/day Anakinra IV Anakinra 4mg/kg/day x 7 days Anakinra 8 mg/kg/day Anakinra IV Anakinra 8 mg/kg/day x 7 days Anakinra 16 mg/kg/day Anakinra IV Anakinra 16 mg/kg/day x 7 days Anakinra 12 mg/kg/day Anakinra IV Anakinra 12 mg/kg/day x 7 days
- Primary Outcome Measures
Name Time Method Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD-2) score 28 days from randomization The cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score over 28 days from randomization. The range of daily PELOD-2 scores is from 0 - 33, with higher scores representing worse organ function.
- Secondary Outcome Measures
Name Time Method 3-month functional status 3 months post-randomization The change in Functional Status Score (FSS) from baseline to 3-months post-randomization. The FSS score ranges from 6 - 30, with higher scores indicating worse functional status.
3-month health-related quality of life 3 months post-randomization The change in Pediatric Quality of Life inventory (PedsQL) score from baseline to 3-months post-randomization. The PedsQL score ranges from 0 - 100, with higher values indicating better quality of life.
Trial Locations
- Locations (27)
University of California, Davis
🇺🇸Sacremento, California, United States
Riley Children's Hospital
🇺🇸Indianapolis, Indiana, United States
Cincinnati Children's Hospital Medical Center
🇺🇸Cincinnati, Ohio, United States
Arkansas Children's Hospital
🇺🇸Little Rock, Arkansas, United States
Children's Hospital of Los Angeles
🇺🇸Los Angeles, California, United States
Benioff Children's Hospital - Oakland
🇺🇸Oakland, California, United States
Children's Hospital of Orange County
🇺🇸Orange, California, United States
Benioff Children's Hospital - Mission Bay
🇺🇸San Francisco, California, United States
Children's Hospital Colorado
🇺🇸Aurora, Colorado, United States
Children's National Medical Center
🇺🇸Washington, District of Columbia, United States
CS Mott Children's Hospital
🇺🇸Ann Arbor, Michigan, United States
Children's Hospital of Michigan
🇺🇸Detroit, Michigan, United States
Children's Hospital of Minnesota
🇺🇸Minneapolis, Minnesota, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Mercy Children's Hospital
🇺🇸Kansas City, Missouri, United States
Duke University
🇺🇸Durham, North Carolina, United States
Rainbow Babies and Children's Hospital
🇺🇸Cleveland, Ohio, United States
Nationwide Children's Hospital
🇺🇸Columbus, Ohio, United States
Pennsylvania State University
🇺🇸Hershey, Pennsylvania, United States
Children's Hospital of Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Children's Hospital of Pittsburgh
🇺🇸Pittsburgh, Pennsylvania, United States
Medical University of South Carolina
🇺🇸Charleston, South Carolina, United States
Texas Children's Hospital
🇺🇸Houston, Texas, United States
Children's Hospital of San Antonio
🇺🇸San Antonio, Texas, United States
Primary Children's Hospital
🇺🇸Salt Lake City, Utah, United States
Virginia Commonwealth University
🇺🇸Richmond, Virginia, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States