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

• ClinicalTrials.gov Identifier: NCT05267821
• Recruitment Status: Recruiting
• First Posted: March 4, 2022
• Last Update Posted: February 8, 2023
• Sponsor: Nationwide Children's Hospital
• Collaborator: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Information provided by (Responsible Party): Mark Hall, Nationwide Children's Hospital

Tracking Information

• First Submitted Date: February 24, 2022
• First Posted Date: March 4, 2022
• Last Update Posted Date: February 8, 2023
• Actual Study Start Date: June 14, 2022
• Estimated Primary Completion Date: May 15, 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 4, 2022)

Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD-2) score [ Time Frame: 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.

Original Primary Outcome Measures (submitted: February 24, 2022)

Cumulative 28-day PELOD-2 score [ Time Frame: 28 days from randomization ]

The cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score over 28 days from randomization

Current Secondary Outcome Measures (submitted: March 4, 2022)

• 3-month health-related quality of life [ Time Frame: 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 [ Time Frame: 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.

Original Secondary Outcome Measures (submitted: February 24, 2022)

• 3-month health-related quality of life [ Time Frame: 3 months post-randomization ]
  The change in PedsQL score from baseline to 3-months post-randomization
• 3-month functional status [ Time Frame: 3 months post-randomization ]
  The change in Functional Status Score from baseline to 3-months post-randomization

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS
• Official Title: Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS (TRIPS)
• 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 Type: Interventional
• Study Phase: Phase 2; Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:

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

Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment

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

Intervention

• Drug: Anakinra
  See information in arm/group descriptions
• Drug: Placebo
  See information in arm/group descriptions

Study Arms

• Active Comparator: Anakinra 4 mg/kg/day
  IV Anakinra 4mg/kg/day x 7 days
  Intervention: Drug: Anakinra
• Active Comparator: Anakinra 8 mg/kg/day
  IV Anakinra 8 mg/kg/day x 7 days
  Intervention: Drug: Anakinra
• Active Comparator: Anakinra 12 mg/kg/day
  IV Anakinra 12 mg/kg/day x 7 days
  Intervention: Drug: Anakinra
• Active Comparator: Anakinra 16 mg/kg/day
  IV Anakinra 16 mg/kg/day x 7 days
  Intervention: Drug: Anakinra
• Placebo Comparator: Placebo
  IV placebo x 7 days
  Intervention: Drug: Placebo

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Recruiting
• Estimated Enrollment (submitted: February 24, 2022): 500
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: August 31, 2027
• Estimated Primary Completion Date: May 15, 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 1 Day to 17 Years (Child)
• Accepts Healthy Volunteers: No

Contacts

Contact: Mark Hall, MD; 6147223438; mark.hall@nationwidechildrens.org

• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05267821
• Other Study ID Numbers: TRIPS
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Current Responsible Party: Mark Hall, Nationwide Children's Hospital
• Original Responsible Party: Same as current
• Current Study Sponsor: Nationwide Children's Hospital
• Original Study Sponsor: Same as current
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
• Investigators: Not Provided
• PRS Account: Nationwide Children's Hospital
• Verification Date: February 2023