Pediatric Sepsis-induced Multiple Organ Dysfunction SyndromePhase 3GRACE-2NCT05266001
GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
A Phase 3 study testing GM-CSF in people with Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome, run by Nationwide Children's Hospital at 25 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 1 day to 17 years
- Conditions the study is for
- Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome
- What is being tested?
- GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 141 participants
- Where
- 25 sitesUnited States
- Study dates
- 14 Jun 2022to 10 Sep 2025
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 day to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- ≥ 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.
Who cannot join
- 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
Show all 13Show fewer
- 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.
Trial locations and contacts
25 sites in 1 country.
25 sites in 1 country
United States25 sites
CS Mott Children's Hospital
Ann Arbor, Michigan, 48109
Children's Hospital Colorado
Aurora, Colorado, 80045
Medical University of South Carolina
Charleston, South Carolina, 29425
Rainbow Babies and Children's Hospital
Cleveland, Ohio, 44106
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Hospital of Michigan
Detroit, Michigan, 48202
Duke University
Durham, North Carolina, 27705
Pennsylvania State University
Hershey, Pennsylvania, 17033
Texas Children's Hospital
Houston, Texas, 77030
Mercy Children's Hospital
Kansas City, Missouri, 64108
Arkansas Children's Hospital
Little Rock, Arkansas, 72202
Children's Hospital of Los Angeles
Los Angeles, California, 90027
Medical College of Wisconsin
Milwaukee, Wisconsin, 53233
Children's Hospital of Minnesota
Minneapolis, Minnesota, 55404
University of Minnesota
Minneapolis, Minnesota, 55455
Benioff Children's Hospital - Oakland
Oakland, California, 64609
Children's Hospital of Orange County
Orange, California, 92868
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15260
Virginia Commonwealth University
Richmond, Virginia, 23298
University of California - Davis
Sacramento, California, 95618
Primary Children's Hospital
Salt Lake City, Utah, 84158
Children's Hospital of San Antonio
San Antonio, Texas, 78207
Benioff Children's Hospital - Mission Bay
San Francisco, California, 94143
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
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.
Read the 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.
- Being tested
- GM-CSF, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFDrug
same as arm/group description
PlaceboOther
same as arm/group description
| Study group | Role | What they receive |
|---|---|---|
| GM-CSF | Active comparator | Intravenous GM-CSF 125 mcg/m2/day x 7 days Receives: Drug: GM-CSF |
| Placebo | Placebo comparator | Intravenous placebo x 7 days Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 28 days from randomization
Secondary outcomes (2)
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.
Measured: 3 months post-randomization
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.
Measured: 3 months post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Mar 2022
- Study start14 Jun 2022
- Primary completion10 Sep 2025
- Study completion10 Sep 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pediatric Sepsis-induced Multiple Organ Dysfunction SyndromeStudies of the same condition, open and under way.
- More trials run by Nationwide Children's HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Prospective, randomized, double-blind, placebo-controlled clinical trial of the drug GM-CSF vs placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 141 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Responsible party
- Principal investigator, Mark Hall, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05266001
- Sponsor's protocol ID
- GRACE-2
- Acronym
- GRACE-2
- Status last verified
- Apr 2026
- First submitted
- 23 Feb 2022
- Last updated
- 9 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
VanBuren JM, Hall M, Zuppa AF, Mourani PM, Carcillo J, Dean JM, Watt K, Holubkov R. The Design of Nested Adaptive Clinical Trials of Multiple Organ Dysfunction Syndrome Children in a Single Study. Pediatr Crit Care Med. 2023 Dec 1;24(12):e635-e646. doi: 10.1097/PCC.0000000000003332. Epub 2023 Jul 27.
PubMed 37498156
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GM-CSF for Reversal of Immunoparalysis in Pediatric Sepsis-induced MODS
- ClinicalTrials.gov ID
- NCT05266001
- Acronym / sponsor ID
- GRACE-2 / GRACE-2
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 141 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Collaborators
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
- Study start
- 14 Jun 2022 (actual)
- Primary completion
- 10 Sep 2025 (actual)
- Study completion
- 10 Sep 2025 (actual)
- First posted
- 4 Mar 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Prospective, randomized, double-blind, placebo-controlled clinical trial of the drug GM-CSF vs placebo
| Arm | Type | Receives |
|---|---|---|
| GM-CSF | Active comparator | Drug: GM-CSFIntravenous GM-CSF 125 mcg/m2/day x 7 days |
| Placebo | Placebo comparator | Other: PlaceboIntravenous placebo x 7 days |
Who may qualify
- Ages
- 1 day to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- ≥ 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.
Key exclusion criteria (13 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GM-CSFsame as arm/group description | Drug | GM-CSF |
| Placebosame as arm/group description | Other | Placebo |
Primary outcome
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.
2 secondary outcomes
3-month health-related quality of life
Time frame: 3 months post-randomization
3-month functional status
Time frame: 3 months post-randomization
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2026.
- Derived from this study: PubMed 37498156VanBuren JM, Hall M, Zuppa AF, Mourani PM, Carcillo J, Dean JM, Watt K, Holubkov R. The Design of Nested Adaptive Clinical Trials of Multiple Organ Dysfunction Syndrome Children in a Single Study. Pediatr Crit Care Med. 2023 Dec 1;24(12):e635-e646. doi: 10.1097/PCC.0000000000003332. Epub 2023 Jul 27.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
25 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing GM-CSF in people with Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome, run by Nationwide Children's Hospital at 25 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 9 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative 28-day Pediatric Logistic Organ Dysfunction (PELOD)-2 score (time frame: 28 days from randomization). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05266001, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Apr 2026.