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NCT05267821PHASE2, PHASE3Recruiting

Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS

Nationwide Children's Hospital

Start Date

6/14/2022

Completion Date

8/31/2028

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.

Eligibility Criteria

Age Range: No minimum to 17 years

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.

Interventions

DRUG

Anakinra

DRUG

Placebo

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Conditions

Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)

Locations

Children's of Alabama

Birmingham, Alabama 35233

United States

Arkansas Children's Hospital

Little Rock, Arkansas 72202

United States

Children's Hospital of Los Angeles

Los Angeles, California 90027

United States

Benioff Children's Hospital - Oakland

Oakland, California 64609

United States

Children's Hospital of Orange County

Orange, California 92868

United States

University of California, Davis

Sacramento, California 95817

United States

Rady Children's Hospital

San Diego, California 92123

United States

Benioff Children's Hospital - Mission Bay

San Francisco, California 94143

United States

Children's Hospital Colorado

Aurora, Colorado 80045

United States

Children's National Medical Center

Washington D.C., District of Columbia 20010

United States

Children's Hospital of Atlanta

Atlanta, Georgia 30329

United States

Riley Children's Hospital

Indianapolis, Indiana 46204

United States

CS Mott Children's Hospital

Ann Arbor, Michigan 48109

United States

Children's Hospital of Michigan

Detroit, Michigan 48201

United States

Children's Hospital of Minnesota

Minneapolis, Minnesota 55404

United States

University of Minnesota

Minneapolis, Minnesota 55455

United States

Mercy Children's Hospital

Kansas City, Missouri 64108

United States

Duke University

Durham, North Carolina 27705

United States

Akron Children's Hospital

Akron, Ohio 44308

United States

Cincinnati Children's Hospital Medical Center

Cincinnati, Ohio 45229

United States

Rainbow Babies and Children's Hospital

Cleveland, Ohio 44106

United States

Nationwide Children's Hospital

Columbus, Ohio 43205

United States

Pennsylvania State University

Hershey, Pennsylvania 17033

United States

Children's Hospital of Philadelphia

Philadelphia, Pennsylvania 19104

United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania 15260

United States

Medical University of South Carolina

Charleston, South Carolina 29425

United States

University of Texas Southwestern

Dallas, Texas 75390

United States

Texas Children's Hospital

Houston, Texas 77030

United States

Children's Hospital of San Antonio

San Antonio, Texas 78207

United States

Primary Children's Hospital

Salt Lake City, Utah 84158

United States

Virginia Commonwealth University

Richmond, Virginia 23298

United States

Medical College of Wisconsin

Milwaukee, Wisconsin 53233

United States