Phase 3
N=1,200
STeroids to REduce Systemic Inflammation After Infant Heart Surgery
Congenital Heart Disease in Children · Inflammatory Response
Bottom Line
View on ClinicalTrials.gov: NCT03229538 ↗Enrolled (actual)
1,200
Serious AEs
0.2%
Results posted
May 2023
Primary outcome: Primary: Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome — 12; 17; 3; 7 Participants — p=0.14
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 3
- Interventions
- Methylprednisolone (Drug); Isotonic saline (Drug)
- Age
- Pediatric
- Sex
- All
- Sponsor
- Kevin Hill
- Primary completion
- Mar 2022
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome |
12; 17; 3; 7; 4; 8 | 0.14 |
| SECONDARY Number of Participants With Mortality, Including In-hospital Mortality or Mortality After Hospital Discharge But Within 30 Days of the Last Dose of Study Drug |
12; 17 | 0.428 |
| SECONDARY Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories |
103; 122 | 0.228 |
| SECONDARY Number of Participants With a Post-operative Length of Stay Greater Than 90 Days |
18; 29 | — |
| SECONDARY Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days) |
41; 51 | 0.309 |
| SECONDARY Number of Participants With Post-operative Low Cardiac Output Syndrome |
31; 37 | 0.723 |
| SECONDARY Number of Participants With Occurrence of Any One or More of the Following STS-CHSD-defined Major Post-operative Infectious Complications: Postprocedural Infective Endocarditis, Pneumonia, Sepsis, Deep Wound Infection, Mediastinitis. |
31; 24 | — |
| SECONDARY Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge. |
237; 264 | 0.256 |
| SECONDARY PK/PD - Time to Maximum Concentration (Tmax) |
— | — |
| SECONDARY PK/PD - Maximum Concentration (Cmax) |
— | — |
| SECONDARY PK/PD - Clearance (CL) |
— | — |
| SECONDARY PK/PD - Volume of Distribution (Vd) |
— | — |
| SECONDARY Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8 |
— | — |
Summary
This study's objective is to determine the pharmacokinetics (PK)/pharmacodynamics (PD), safety and efficacy of methylprednisolone in infants undergoing heart surgery with cardiopulmonary bypass. This is a prospective, double blind, multi-center, placebo-controlled safety and efficacy study. Blood samples will be collected from a subset of enrolled study participants to evaluate multiple dose methylprednisolone PK/PD. Participants will be randomized in a 1:1 fashion to intravenous methylprednisolone versus placebo. Study drug/placebo will be administered 8 to 12 hours before the anticipated start time of surgery and in the operating room at the time of initiation of cardiopulmonary bypass. Patients will be followed for primary and secondary outcomes for the duration of their hospitalization. Serious study drug-related adverse events will be collected for 7 days after the last dose of study drug.
Eligibility Criteria
Inclusion Criteria
- Age < 1 year at the time of surgery
- Undergoing heart surgery with CPB as part of standard clinical care
- Availability and willingness of the parent/legally authorized representative to provide written informed consent
Exclusion Criteria
- < 37 weeks adjusted gestational age at time of surgery
- Any oral or intravenous steroid treatment within two days of surgery
- Any patient receiving any of the following medications within 2 days of surgery:
Amphotericin B, aminoglutethimide, anticholinesterases, warfarin, P450 3A4 inducers including (but not limited to) carbamazepine, phenobarbital, phenytoin, rifampin, bosentan and nafcillin or P450 3A4 inhibitors including (but not limited to) clarithromycin, voriconazole, itraconazole, ketoconazole, ciprofloxacin, diltiazem, fluconazole, erythromycin and verapamil.
- Infection contraindicating steroid use
- Preoperative mechanical circulatory support or active resuscitation at the time of randomization
- Emergent surgery precluding steroid administration 8-12 hours before surgery
Data sourced from ClinicalTrials.gov (NCT03229538). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.