Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)

Nationwide Children's Hospital

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)

Treatments: Drug: Anakinra; Drug: Placebo

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT05267821

TRIPS

Details and patient eligibility

About

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).

Full 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.

Enrollment: 500 estimated patients

Sex: All

Ages: 1 day to 17 years old

Volunteers: No Healthy Volunteers

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
• 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 therapy OR 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 within the previous 28 days; OR
• Resolution of MODS by MODS Day 2; OR
• Previous enrollment in the TRIPS study.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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500 participants in 5 patient groups, including a placebo group

Anakinra 4 mg/kg/day

Active Comparator group

Description:

IV Anakinra 4mg/kg/day x 7 days

Treatment:

Drug: Anakinra

Anakinra 8 mg/kg/day

Active Comparator group

Description:

IV Anakinra 8 mg/kg/day x 7 days

Treatment:

Drug: Anakinra

Anakinra 12 mg/kg/day

Active Comparator group

Description:

IV Anakinra 12 mg/kg/day x 7 days

Treatment:

Drug: Anakinra

Anakinra 16 mg/kg/day

Active Comparator group

Description:

IV Anakinra 16 mg/kg/day x 7 days

Treatment:

Drug: Anakinra

Placebo

Placebo Comparator group

Description:

IV placebo x 7 days

Treatment:

Drug: Placebo