Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS

Phase 2

Recruiting

• Conditions: Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
• Interventions: Drug: Placebo; Drug: Anakinra

• 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.

Study Timeline

• Study First Submitted: 2022-02-24
• Study First Submitted QC: 2022-02-24
• Study First Posted: 2022-03-04
• Study Start: 2022-06-14
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-02
• Last Update Posted: 2025-07-08
• Primary Completion: 2027-05-15
• Study Completion: 2027-08-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 500

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.

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 (29)

Rady Children's Hospital; 🇺🇸 San Diego, California, United States

University of Texas Southwestern; 🇺🇸 Dallas, Texas, 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

University of California, Davis; 🇺🇸 Sacramento, 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

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