search
Back to results

GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS (GRACE-2)

Primary Purpose

Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Status
Recruiting
Phase
Phase 3
Locations
United States
Study Type
Interventional
Intervention
GM-CSF
Placebo
Sponsored by
Nationwide Children's Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

Eligibility Criteria

1 Day - 17 Years (Child)All SexesDoes not accept 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 therapy OR receipt of myeloablative therapy within the previous 14 days; OR
  • Known allergy to GM-CSF; 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 GRACE-2 study.

Sites / Locations

  • Arkansas Children's HospitalRecruiting
  • Children's Hospital of Los AngelesRecruiting
  • Benioff Children's Hospital - OaklandRecruiting
  • Children's Hospital of Orange County
  • University of California - DavisRecruiting
  • Benioff Children's Hospital - Mission BayRecruiting
  • Children's Hospital ColoradoRecruiting
  • Children's National Medical CenterRecruiting
  • CS Mott Children's HospitalRecruiting
  • Children's Hospital of MichiganRecruiting
  • Children's Hospital of Minnesota
  • University of MinnesotaRecruiting
  • Mercy Children's HospitalRecruiting
  • Duke UniversityRecruiting
  • Rainbow Babies and Children's HospitalRecruiting
  • Nationwide Children's HospitalRecruiting
  • Pennsylvania State UniversityRecruiting
  • Children's Hospital of PhiladelphiaRecruiting
  • Children's Hospital of PittsburghRecruiting
  • Medical University of South CarolinaRecruiting
  • Texas Children's HospitalRecruiting
  • Children's Hospital of San AntonioRecruiting
  • Primary Children's HospitalRecruiting
  • Virginia Commonwealth UniversityRecruiting
  • Medical College of Wisconsin

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

GM-CSF

Placebo

Arm Description

Intravenous GM-CSF 125 mcg/m2/day x 7 days

Intravenous placebo x 7 days

Outcomes

Primary Outcome Measures

Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score
Cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score through 28 days post-randomization. The range of PELOD-2 score for a given day is 0 - 33 with a higher number being worse.

Secondary Outcome Measures

3-month health-related quality of life
Change in Pediatric Quality of Life inventory (PedsQL) score from baseline to 3 months post-randomization. The range of PedsQL scores is from 0 - 100, with higher values corresponding to better quality of life.
3-month functional status
Change in Functional Status Score from baseline to 3 months post-randomization. The range of possible FSS score for a given subject is 6 - 30 with a higher score indicating worse function.

Full Information

First Posted
February 23, 2022
Last Updated
February 7, 2023
Sponsor
Nationwide Children's Hospital
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
search

1. Study Identification

Unique Protocol Identification Number
NCT05266001
Brief Title
GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
Acronym
GRACE-2
Official Title
GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
Study Type
Interventional

2. Study Status

Record Verification Date
February 2023
Overall Recruitment Status
Recruiting
Study Start Date
June 14, 2022 (Actual)
Primary Completion Date
May 31, 2027 (Anticipated)
Study Completion Date
August 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Nationwide Children's Hospital
Collaborators
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The GRACE-2 study is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation.
Detailed Description
The GRACE-2 study is a is a prospective, multi-center, double-blind, randomized controlled trial of the drug GM-CSF vs placebo in children with sepsis-induced multiple organ dysfunction syndrome (MODS) who have immunoparalysis with mild to moderate inflammation. Eligible subjects will undergo centralized immunophenotyping on MODS Day 2. Those who are found to have immunoparalysis (a whole blood LPS-induced TNF-alpha production capacity < 200 pg/ml) with mild to moderate inflammation (serum ferritin level < 2000 ng/ml) will be randomized to receive intravenous (IV) GM-CSF at a dose of 125 mcg/m2/day x 7 days or placebo. The primary outcome variable is the cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score. Secondary outcomes include measures of health-related quality of life and function status at 3 months from randomization.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Model Description
Prospective, randomized, double-blind, placebo-controlled clinical trial
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
400 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
GM-CSF
Arm Type
Active Comparator
Arm Description
Intravenous GM-CSF 125 mcg/m2/day x 7 days
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Intravenous placebo x 7 days
Intervention Type
Drug
Intervention Name(s)
GM-CSF
Intervention Description
same as arm/group description
Intervention Type
Other
Intervention Name(s)
Placebo
Intervention Description
same as arm/group description
Primary Outcome Measure Information:
Title
Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score
Description
Cumulative Pediatric Logistic Organ Dysfunction (PELOD)-2 score through 28 days post-randomization. The range of PELOD-2 score for a given day is 0 - 33 with a higher number being worse.
Time Frame
28 days from randomization
Secondary Outcome Measure Information:
Title
3-month health-related quality of life
Description
Change in Pediatric Quality of Life inventory (PedsQL) score from baseline to 3 months post-randomization. The range of PedsQL scores is from 0 - 100, with higher values corresponding to better quality of life.
Time Frame
3 months post-randomization
Title
3-month functional status
Description
Change in Functional Status Score from baseline to 3 months post-randomization. The range of possible FSS score for a given subject is 6 - 30 with a higher score indicating worse function.
Time Frame
3 months post-randomization

10. Eligibility

Sex
All
Minimum Age & Unit of Time
1 Day
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
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 therapy OR receipt of myeloablative therapy within the previous 14 days; OR Known allergy to GM-CSF; 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 GRACE-2 study.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Mark W Hall, MD
Phone
6147223438
Email
mark.hall@nationwidechildrens.org
Facility Information:
Facility Name
Arkansas Children's Hospital
City
Little Rock
State/Province
Arkansas
ZIP/Postal Code
72202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ronald Sanders
Facility Name
Children's Hospital of Los Angeles
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robinder Khemani
Facility Name
Benioff Children's Hospital - Oakland
City
Oakland
State/Province
California
ZIP/Postal Code
64609
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Natalie Cvijanovich
Facility Name
Children's Hospital of Orange County
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Adam Schwarz
Facility Name
University of California - Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95618
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Moonjoo Han
Facility Name
Benioff Children's Hospital - Mission Bay
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Patrick McQuillen
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Eva Nozik
Facility Name
Children's National Medical Center
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20010
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Bell
Facility Name
CS Mott Children's Hospital
City
Ann Arbor
State/Province
Michigan
ZIP/Postal Code
48109
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Michael Quasney
Facility Name
Children's Hospital of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kathleen Meert
Facility Name
Children's Hospital of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55404
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Alberto Orioles
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marie Steiner
Facility Name
Mercy Children's Hospital
City
Kansas City
State/Province
Missouri
ZIP/Postal Code
64108
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Yong Han
Facility Name
Duke University
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27705
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Christoph Hornik
Facility Name
Rainbow Babies and Children's Hospital
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Steven Shein
Facility Name
Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43205
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mark Hall
Phone
614-722-3438
Email
mark.hall@nationwidechildrens.org
Facility Name
Pennsylvania State University
City
Hershey
State/Province
Pennsylvania
ZIP/Postal Code
17033
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Neal Thomas
Facility Name
Children's Hospital of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Robert Berg
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15260
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Joseph Carcillo
Facility Name
Medical University of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
29425
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
John Costello
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ayse Arikan
Facility Name
Children's Hospital of San Antonio
City
San Antonio
State/Province
Texas
ZIP/Postal Code
78207
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Mohammed Salameh
Facility Name
Primary Children's Hospital
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84158
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Jill Sweney
Facility Name
Virginia Commonwealth University
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23298
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nikki Miller-Ferguson
Facility Name
Medical College of Wisconsin
City
Milwaukee
State/Province
Wisconsin
ZIP/Postal Code
53233
Country
United States
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nathan Thompson

12. IPD Sharing Statement

Plan to Share IPD
Undecided

Learn more about this trial

GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS

We'll reach out to this number within 24 hrs