Pediatric Sepsis-induced MODSPhase 4GRACENCT03769844
GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS Study
A Phase 4 study testing GM-CSF in people with Pediatric Sepsis-induced MODS, run by Nationwide Children's Hospital at 8 sites in United States.
Trial summary
This study is an open-label, multi-center, interventional trial in which children with sepsis-induced MODS undergo surveillance immune function testing beginning on Day 2 of MODS. Read more about this study
- Who is it for?
- Ages Up to 17 years
- Conditions the study is for
- Pediatric Sepsis-induced MODS
- What is being tested?
- GM-CSF
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 75 participants
- Where
- 8 sitesUnited States
- Study dates
- 5 Dec 2018to 5 Dec 2023
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 Up to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- >= 40 weeks gestational age to <18 years; AND
- Onset of >=2 new organ dysfunctions (compared to pre-sepsis baseline) as measured by the Proulx criteria; AND
- Documented or suspected infection as the MODS inciting event.
Who cannot join
- Unable to collect a cumulative total of 20.5 mL of blood for this study due to research blood draw limits; OR
- Limitation of care order at the time of screening; OR
- Patients at high risk for brain death; OR
- Active (or planned within 7 days) immunosuppressive treatment for oncologic, transplant, or rheumatologic disease; OR
- Known primary immunodeficiency disorder; OR
- Diagnosis of myeloid leukemia, myelodysplasia, or autoimmune thrombocytopenia;OR
Show all 15Show fewer
- Known allergy to GM-CSF; OR
- Documented hyperferritinemia (serum ferritin >= 500 ng/ml) during current sepsis event; OR
- Contraindication to SQ injection (ECMO); OR
- Burns where >5% of the total body surface area is affected; OR
- Renal replacement therapy at the time of screening; OR
- On ECMO or anticipated to require ECMO; OR
- Known pregnancy; OR
- Inability to collect and ship sample for immune testing on MODS Day 2; OR
- Previous enrollment in the GRACE study
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
Children's Hospital of Colorado
Aurora, Colorado, 80045
Nationwide Children's Hospital
Columbus, Ohio, 43205
Children's Hospital of Michigan
Detroit, Michigan, 48201
UCLA Mattel Children's Hospital
Los Angeles, California, 90095
Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
Children's Hospital of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Benioff Children's Hospital/UCSF
San Francisco, California, 94158
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: GM-CSF for Reversal of immunopAralysis in pediatriC sEpsis-induced MODS (GRACE)
This study is an open-label, multi-center, interventional trial in which children with sepsis-induced MODS undergo surveillance immune function testing beginning on Day 2 of MODS. Those children who demonstrate immunoparalysis (TNF-alpha response <200 pg/ml) will receive a 7-day course of GM-CSF at a dose of 125 or 250 mcg/m2/day by either the intravenous (IV) or subcutaneous (SQ) route.
The goal of the study is to establish the dose and route of delivery that results in resolution of immunoparalysis (TNF-alpha response >=200 pg/ml) by the morning after the 3rd scheduled dose with persistent resolution of immunoparalysis on the morning after the 7th scheduled dose. Resolution of immunoparalysis in 8 out of the first 10 subjects in a study treatment arm represents a successful dose and route. The goal of this study will be achieved through the following Specific Aims:
Read more
Specific Aim 1. Establish the immunologic efficacy of GM-CSF administered by the IV and SQ routes in children with immunoparalysis in the setting of sepsis-induced MODS.
Specific Aim 2. Estimate the pharmacokinetic parameters by the IV and SQ GM-CSF administered in pediatric sepsis-induced MODS.
Specific Aim 3. Demonstrate the feasibility of screening, enrollment, drug delivery, and sample collection for a multi-center immunostimulation trial in children with sepsis-induced MODS.
- Conditions
- Pediatric Sepsis-induced MODS
- Being tested
- GM-CSF
- Keywords
- sepsis, MODS, pediatric, immunoparalysis, GM-CSF
- Medical subject headings
- Sepsis, Multiple Organ Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GM-CSFDrug
Also called granulocyte macrophage colony-stimulating factor, Leukine
Subjects demonstrating immunoparalysis (defined by a whole blood ex vivo LP-induced TNF-alpha production capacity < 200 pg/ml) will receive 7 days of GM-CSF treatment by either the IV or SQ route at a dose of either 125 or 250 mcg/m2/day for 7 days.
| Study group | Role | What they receive |
|---|---|---|
| IV GM-CSF 125 mcg/m2/dose | Experimental | Subjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the intravenous (IV) route at a dose of 125 mcg/m2/day for 7 consecutive days. Receives: Drug: GM-CSF |
| SQ GM-CSF 125 mcg/m2/dose | Experimental | Subjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the subcutaneous (SQ) route at a dose of 125 mcg/m2/day for 7 consecutive days. Receives: Drug: GM-CSF |
| IV GM-CSF 250 mcg/m2/dose | Experimental | If the IV 125 mcg/m2/dose arm is not successful in the first cohort of subjects, we will transition to 250 mcg/m2/day via the IV route for 7 consecutive days in a subsequent cohort. Receives: Drug: GM-CSF |
| SQ GM-CSF 250 mcg/m2/dose | Experimental | If the SQ 125 mcg/m2/dose arm is not successful in a cohort of subjects (or if the IV dose had to be escalated to 250 mcg/m2/dose), we will transition to 250 mcg/m2/day via the SQ route for 7 consecutive days in a subsequent cohort. Receives: Drug: GM-CSF |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Subjects With Restoration of the TNF-alpha Response
Success in a cohort is defined as improvement in the whole blood ex vivo LPS-induced TNF-alpha production capacity (TNF response) to >= 200 pg/ml by the morning after the 3rd dose and persisting to the morning after the 7th dose in at least 8 out of 10 treated subjects within a cohort
Measured: Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2018
- Study start5 Dec 2018
- Primary completion5 Dec 2023
- Study completion5 Dec 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Pediatric Sepsis-induced MODSStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- This is an open-label, sequential, dose- and route of administration-finding study that will be conducted in sequential cohorts of children with sepsis-induced MODS
- Masking
- None (open label)
- Enrolment
- 75 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nationwide Children's Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mark Hall, Nationwide Children's Hospital
- Investigators
- Mark W Hall, MD, Principal investigator, Nationwide Children's Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03769844
- Sponsor's protocol ID
- GRACE
- Acronym
- GRACE
- Status last verified
- Apr 2026
- First submitted
- 6 Dec 2018
- Last updated
- 5 May 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: After subject enrollment and follow up have been completed, the DCC will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers.
Study at a glance
From the registry record, last updated by the sponsor on 5 May 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 (GRACE)
- ClinicalTrials.gov ID
- NCT03769844
- Acronym / sponsor ID
- GRACE / GRACE
- Conditions
- Pediatric Sepsis-induced MODS
- Keywords
- sepsis, MODS, pediatric, immunoparalysis, GM-CSF
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 75 participants (actual)
- Lead sponsor
- Nationwide Children's HospitalUniversity, hospital or other
- Study start
- 5 Dec 2018 (actual)
- Primary completion
- 5 Dec 2023 (actual)
- Study completion
- 5 Dec 2023 (actual)
- First posted
- 10 Dec 2018 (actual)
- Results
- Posted 5 May 2026
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is an open-label, multi-center, interventional trial in which children with sepsis-induced MODS undergo surveillance immune function testing beginning on Day 2 of MODS. Those children who demonstrate immunoparalysis (TNF-alpha response <200 pg/ml) will receive a 7-day course of GM-CSF at a dose of 125 or 250 mcg/m2/day by either the intravenous (IV) or subcutaneous (SQ) route.
The goal of the study is to establish the dose and route of delivery that results in resolution of immunoparalysis (TNF-alpha response >=200 pg/ml) by the morning after the 3rd scheduled dose with persistent resolution of immunoparalysis on the morning after the 7th scheduled dose. Resolution of immunoparalysis in 8 out of the first 10 subjects in a study treatment arm represents a successful dose and route. The goal of this study will be achieved through the following Specific Aims:
Specific Aim 1. Establish the immunologic efficacy of GM-CSF administered by the IV and SQ routes in children with immunoparalysis in the setting of sepsis-induced MODS.
Specific Aim 2. Estimate the pharmacokinetic parameters by the IV and SQ GM-CSF administered in pediatric sepsis-induced MODS.
Specific Aim 3. Demonstrate the feasibility of screening, enrollment, drug delivery, and sample collection for a multi-center immunostimulation trial in children with sepsis-induced MODS.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
- Model description
- This is an open-label, sequential, dose- and route of administration-finding study that will be conducted in sequential cohorts of children with sepsis-induced MODS
| Arm | Type | Receives |
|---|---|---|
| IV GM-CSF 125 mcg/m2/dose | Experimental | Drug: GM-CSFSubjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the intravenous (IV) route at a dose of 125 mcg/m2/day for 7 consecutive days. |
| SQ GM-CSF 125 mcg/m2/dose | Experimental | Drug: GM-CSFSubjects in this arm who demonstrate immunoparalysis will receive GM-CSF by the subcutaneous (SQ) route at a dose of 125 mcg/m2/day for 7 consecutive days. |
| IV GM-CSF 250 mcg/m2/dose | Experimental | Drug: GM-CSFIf the IV 125 mcg/m2/dose arm is not successful in the first cohort of subjects, we will transition to 250 mcg/m2/day via the IV route for 7 consecutive days in a subsequent cohort. |
| SQ GM-CSF 250 mcg/m2/dose | Experimental | Drug: GM-CSFIf the SQ 125 mcg/m2/dose arm is not successful in a cohort of subjects (or if the IV dose had to be escalated to 250 mcg/m2/dose), we will transition to 250 mcg/m2/day via the SQ route for 7 consecutive days in a subsequent cohort. |
Who may qualify
- Ages
- Up to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (3 listed)
- >= 40 weeks gestational age to <18 years; AND
- Onset of >=2 new organ dysfunctions (compared to pre-sepsis baseline) as measured by the Proulx criteria; AND
- Documented or suspected infection as the MODS inciting event.
Key exclusion criteria (15 listed)
- Unable to collect a cumulative total of 20.5 mL of blood for this study due to research blood draw limits; OR
- Limitation of care order at the time of screening; OR
- Patients at high risk for brain death; OR
- Active (or planned within 7 days) immunosuppressive treatment for oncologic, transplant, or rheumatologic disease; OR
- Known primary immunodeficiency disorder; 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-CSFAlso: granulocyte macrophage colony-stimulating factor, LeukineSubjects demonstrating immunoparalysis (defined by a whole blood ex vivo LP-induced TNF-alpha production capacity < 200 pg/ml) will receive 7 days of GM-CSF treatment by either the IV or SQ route at a dose of either 125 or 250 mcg/m2/day for 7 days. | Drug | IV GM-CSF 125 mcg/m2/dose, IV GM-CSF 250 mcg/m2/dose, SQ GM-CSF 125 mcg/m2/dose, SQ GM-CSF 250 mcg/m2/dose |
Primary outcome
Number of Subjects With Restoration of the TNF-alpha Response
Time frame: Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS
Success in a cohort is defined as improvement in the whole blood ex vivo LPS-induced TNF-alpha production capacity (TNF response) to >= 200 pg/ml by the morning after the 3rd dose and persisting to the morning after the 7th dose in at least 8 out of 10 treated subjects within a cohort
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 May 2026.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: Yes. After subject enrollment and follow up have been completed, the DCC will prepare a final study database for analysis. A releasable database will be produced and completely de-identified in accordance with the definitions provided in the Health insurance Portability and Accountability Act (HIPAA). Namely, all identifiers specified in HIPAA will be recoded in a manner that will make it impossible to deduce or impute the specific identity of any patient. The database will not contain any institutional identifiers.
Related trials for Pediatric Sepsis-induced MODS
RecruitingPhase 2/3
Targeted Reversal of Inflammation in Pediatric Sepsis-induced MODS
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome (MODS)
Active, not recruitingObservational study
Early Continuous Renal Replacement Therapy for Pediatric Septic Shock
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome, Septic Shock
Not yet recruitingObservational study
The Study Seeks to Determine Potential Correlations Between Ventilation and Hematological Alterations, Contributing to a Better Understanding of Its Physiological Effects and Optimizing Patient Management in Critical Care Settings.
Pediatric Sepsis-induced Multiple Organ Dysfunction Syndrome
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.
Mark W Hall, MD principal investigator
Nationwide Children's Hospital
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing GM-CSF in people with Pediatric Sepsis-induced MODS, run by Nationwide Children's Hospital at 8 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 3 inclusion and 15 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 5 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 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. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 May 2026). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Subjects With Restoration of the TNF-alpha Response (time frame: Subjects will be screened for immunoparalysis throughout their first three weeks of sepsis-induced MODS). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 5 May 2026.