History of Changes for Study: NCT05266001

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

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Study Record Versions

Version	Submitted Date	Changes
1	March 2, 2022	None (earliest Version on record)
2	May 8, 2022	Study Status
3	October 3, 2022	Recruitment Status, Study Status and Contacts/Locations
4	November 15, 2022	Study Status and Contacts/Locations
5	February 7, 2023	Contacts/Locations and Study Status

Comparison Format:

Merged
Side-by-Side

Study Identification


Unique Protocol ID:	GRACE-2
Brief Title:	GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS (GRACE-2)
Official Title:	GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
Secondary IDs:

Study Status


Record Verification:	March 2022
Overall Status:	Not yet recruiting
Study Start:	March 30, 2022
Primary Completion:	August 31, 2027 [Anticipated]
Study Completion:	August 31, 2027 [Anticipated]

First Submitted:	February 23, 2022
First Submitted that Met QC Criteria:	March 2, 2022
First Posted:	March 4, 2022 [Actual]

Last Update Submitted that Met QC Criteria:	March 2, 2022
Last Update Posted:	March 4, 2022 [Actual]

Sponsor/Collaborators


Sponsor:	Nationwide Children's Hospital
Responsible Party:	Principal Investigator Investigator: Mark Hall Official Title: Chief, Critical Care Medicine Affiliation: Nationwide Children's Hospital
Collaborators:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Oversight


U.S. FDA-regulated Drug:	Yes
U.S. FDA-regulated Device:	No
Data Monitoring:	Yes

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.

Conditions


Conditions:	Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome
Keywords:

Study Design


Study Type:	Interventional
Primary Purpose:	Treatment
Study Phase:	Phase 3
Interventional Study Model:	Parallel Assignment
	Prospective, randomized, double-blind, placebo-controlled clinical trial
Number of Arms:	2
Masking:	Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation:	Randomized
Enrollment:	400 [Anticipated]

Arms and Interventions

Arms	Assigned Interventions
Active Comparator: GM-CSF Intravenous GM-CSF 125 mcg/m2/day x 7 days	Drug: GM-CSF same as arm/group description
Placebo Comparator: Placebo Intravenous placebo x 7 days	Placebo same as arm/group description

Outcome Measures


Primary Outcome Measures:
1.	Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score [ Time Frame: 28 days from randomization ] 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:
1.	3-month health-related quality of life [ Time Frame: 3 months post-randomization ] 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.
2.	3-month functional status [ Time Frame: 3 months post-randomization ] 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.

Eligibility


Minimum Age:	1 Day
Maximum Age:	17 Years
Sex:	All
Gender Based:
Accepts Healthy Volunteers:	No
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.

Contacts/Locations


Central Contact Person:	Mark W Hall, MD Telephone: 6147223438 Email: mark.hall@nationwidechildrens.org
Locations:	United States, Arkansas
	Arkansas Children's Hospital Little Rock, Arkansas, United States, 72202 Contact:Contact: Ronald Sanders
	United States, California
	Children's Hospital of Los Angeles Los Angeles, California, United States, 90027 Contact:Contact: Robinder Khemani
	University of California Los Angeles Los Angeles, California, United States, 90095 Contact:Contact: Anil Sapru
	Benioff Children's Hospital - Oakland Oakland, California, United States, 64609
	Children's Hospital of Orange County Orange, California, United States, 92868
	University of California - Davis Sacramento, California, United States, 95618 Contact:Contact: Moonjoo Han
	Benioff Children's Hospital - Mission Bay San Francisco, California, United States, 94143 Contact:Contact: Patrick McQuillen
	United States, Colorado
	Children's Hospital Colorado Aurora, Colorado, United States, 80045 Contact:Contact: Todd Carpenter
	United States, District of Columbia
	Children's National Medical Center Washington, District of Columbia, United States, 20010 Contact:Contact: Michael Bell
	United States, Michigan
	CS Mott Children's Hospital Ann Arbor, Michigan, United States, 48109 Contact:Contact: Michael Quasney
	Children's Hospital of Michigan Detroit, Michigan, United States, 48202 Contact:Contact: Kathleen Meert
	United States, Minnesota
	Children's Hospital of Minnesota Minneapolis, Minnesota, United States, 55404 Contact:Contact: Alberto Orioles
	University of Minnesota Minneapolis, Minnesota, United States, 55455 Contact:Contact: Marie Steiner
	United States, Missouri
	Mercy Children's Hospital Kansas City, Missouri, United States, 64108 Contact:Contact: Yong Han
	United States, North Carolina
	Duke University Durham, North Carolina, United States, 27705
	United States, Ohio
	Rainbow Babies and Children's Hospital Cleveland, Ohio, United States, 44106 Contact:Contact: Steven Shein
	Nationwide Children's Hospital Columbus, Ohio, United States, 43205 Contact:Contact: Mark Hall 614-722-3438 mark.hall@nationwidechildrens.org
	United States, Pennsylvania
	Pennsylvania State University Hershey, Pennsylvania, United States, 17033 Contact:Contact: Neal Thomas
	Children's Hospital of Philadelphia Philadelphia, Pennsylvania, United States, 19104 Contact:Contact: Robert Berg
	Children's Hospital of Pittsburgh Pittsburgh, Pennsylvania, United States, 15260 Contact:Contact: Joseph Carcillo
	United States, South Carolina
	Medical University of South Carolina Charleston, South Carolina, United States, 29425 Contact:Contact: John Costello
	United States, Texas
	Texas Children's Hospital Houston, Texas, United States, 77030 Contact:Contact: Ayse Arikan
	Children's Hospital of San Antonio San Antonio, Texas, United States, 78207
	United States, Utah
	Primary Children's Hospital Salt Lake City, Utah, United States, 84158
	United States, Virginia
	Virginia Commonwealth University Richmond, Virginia, United States, 23298
	United States, Wisconsin
	Medical College of Wisconsin Milwaukee, Wisconsin, United States, 53233 Contact:Contact: Nathan Thompson

IPDSharing


Plan to Share IPD:	Undecided

References


Citations:
Links:
Available IPD/Information: