TRIPS: Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS

Sponsor

Nationwide Children's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05267821

Collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

500

Enrollment

Locations

Arms

63.5

Anticipated Duration (Months)

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Condition or Disease	Intervention/Treatment	Phase
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)	Drug: Anakinra Drug: Placebo	Phase 2/Phase 3

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 Design

Study Type:

Interventional

Anticipated Enrollment :

500 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Prospective, adaptively-randomized, double-blind, placebo controlled clinical trialProspective, adaptively-randomized, double-blind, placebo controlled clinical trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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

Anticipated Study Start Date :

May 15, 2022

Anticipated Primary Completion Date :

May 15, 2027

Anticipated Study Completion Date :

Aug 31, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Anakinra 4 mg/kg/day IV Anakinra 4mg/kg/day x 7 days	Drug: Anakinra See information in arm/group descriptions
Active Comparator: Anakinra 8 mg/kg/day IV Anakinra 8 mg/kg/day x 7 days	Drug: Anakinra See information in arm/group descriptions
Active Comparator: Anakinra 12 mg/kg/day IV Anakinra 12 mg/kg/day x 7 days	Drug: Anakinra See information in arm/group descriptions
Active Comparator: Anakinra 16 mg/kg/day IV Anakinra 16 mg/kg/day x 7 days	Drug: Anakinra See information in arm/group descriptions
Placebo Comparator: Placebo IV placebo x 7 days	Drug: Placebo See information in arm/group descriptions

Outcome Measures

Primary Outcome Measures

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

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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

1 Day to 17 Years

Sexes Eligible for Study:

All

Accepts 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
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Arkansas Children's Hospital	Little Rock	Arkansas	United States	72202
2	Children's Hospital of Los Angeles	Los Angeles	California	United States	90027
3	University of California Los Angeles	Los Angeles	California	United States	90095
4	Benioff Children's Hospital - Oakland	Oakland	California	United States	64609
5	Children's Hospital of Orange County	Orange	California	United States	92868
6	Benioff Children's Hospital - Mission Bay	San Francisco	California	United States	94143
7	Children's Hospital Colorado	Aurora	Colorado	United States	80045
8	Children's National Medical Center	Washington	District of Columbia	United States	20010
9	CS Mott Children's Hospital	Ann Arbor	Michigan	United States	48109
10	Children's Hospital of Michigan	Detroit	Michigan	United States	48201
11	Children's Hospital of Minnesota	Minneapolis	Minnesota	United States	55404
12	University of Minnesota	Minneapolis	Minnesota	United States	55455
13	Mercy Children's Hospital	Kansas City	Missouri	United States	64108
14	Duke University	Durham	North Carolina	United States	27705
15	Rainbow Babies and Children's Hospital	Cleveland	Ohio	United States	44106
16	Nationwide Children's Hospital	Columbus	Ohio	United States	43205
17	Pennsylvania State University	Hershey	Pennsylvania	United States	17033
18	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
19	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15260
20	Medical University of South Carolina	Charleston	South Carolina	United States	29425
21	Texas Children's Hospital	Houston	Texas	United States	77030
22	Children's Hospital of San Antonio	San Antonio	Texas	United States	78207
23	Primary Children's Hospital	Salt Lake City	Utah	United States	84158
24	Virginia Commonwealth University	Richmond	Virginia	United States	23298
25	Medical College of Wisconsin	Milwaukee	Wisconsin	United States	53233

Sponsors and Collaborators

Nationwide Children's Hospital
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Mark Hall, Chief, Division of Critical Care Medicine, Nationwide Children's Hospital

ClinicalTrials.gov Identifier:

NCT05267821

Other Study ID Numbers:

TRIPS

First Posted:

Mar 4, 2022

Last Update Posted:

May 10, 2022

Last Verified:

May 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Undecided

Plan to Share IPD:

Undecided

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Sepsis

Toxemia

Inflammation

Multiple Organ Failure

Interleukin 1 Receptor Antagonist Protein

Study Results

No Results Posted as of May 10, 2022