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STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03229538
Recruitment Status : Recruiting
First Posted : July 25, 2017
Last Update Posted : July 17, 2020
Sponsor:
Information provided by (Responsible Party):
Kevin Hill, Duke University

Brief 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.

Condition or disease Intervention/treatment Phase
Congenital Heart Disease in Children Inflammatory Response Drug: Methylprednisolone Drug: Isotonic saline Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS)
Actual Study Start Date : October 18, 2017
Estimated Primary Completion Date : July 28, 2021
Estimated Study Completion Date : July 28, 2021


Arm Intervention/treatment
Experimental: Methylprednisolone Arm
IV Methylprednisolone
Drug: Methylprednisolone
IV Steroid pre-operative and intra-operative

Placebo Comparator: Placebo Arm
IV Isotonic Saline
Drug: Isotonic saline
Isotonic saline pre-operative and intra-operative




Primary Outcome Measures :
  1. A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity. [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]

    A composite mortality, major morbidity and length of stay global rank endpoint with endpoints ranked according to severity.

    For this endpoint each randomized patient will be assigned a rank based upon their most-severe outcome.



Secondary Outcome Measures :
  1. Mortality including in-hospital mortality or mortality after hospital discharge but within 30 days of the last cardiac operation of the admission [ Time Frame: up to 30 days ]
  2. Death or major complication as previously defined and reported by the STS-CHSD registry. [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  3. Post-operative hospital length of stay [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  4. Prevalence of prolonged (>7days) mechanical ventilation [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  5. Occurrence of post-operative low cardiac output syndrome. Based upon the STS-CHSD registry defined "cardiac dysfunction resulting in low cardiac output" complication variable [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  6. Occurence of any one or more of the following STS-CHSD-defined major post-operative infectious complications: o Postprocedural infective endocarditis o Pneumonia o Sepsis o Deep wound infection o Mediastinitis [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  7. Any other post-operative complications from the start of study drug administration until hospital discharge. [ Time Frame: Until hospital discharge. Length of stay up to 6 months ]
  8. PK/PD - Time to maximum concentration (Tmax) [ Time Frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB) ]
  9. PK/PD - Maximum concentration (Cmax) [ Time Frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB) ]
  10. PK/PD - Clearance (CL) [ Time Frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB) ]
  11. PK/PD - Volume of distribution (Vd) [ Time Frame: Pre-2nd dose and minimum of 2 of any of the following 5 time points (0-30 minutes after the start of CPB, 0-30 minutes after MUF, 1-2 hours after completion of CPB, 4-6 hours after completion of CPB, or 16-24 hours after completion of CPB) ]
  12. Post-operative biomarkers of the inflammatory response to cardiopulmonary bypass including interleukins 6 and 8 [ Time Frame: Pre-2nd dose; a minimum of 2 of any of the following 5 time points (0-30 min after the start of CPB, 0-30 min after MUF, 1-2 hrs after CPB end, 4-6 hrs after CPB end, or 16-24 hrs after CPB end); and 36-48 hrs after CPB end ]
    Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws



Information from the National Library of Medicine

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Ages Eligible for Study:   up to 12 Months   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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:

Amphoteracin B, aminoglutethimide, anticholesterases, 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03229538


Contacts
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Contact: Project Leader 9196681080 dcri-STRESS@duke.edu

Locations
Show Show 22 study locations
Sponsors and Collaborators
Kevin Hill
Investigators
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Principal Investigator: Kevin Hill Duke University
  Study Documents (Full-Text)

Documents provided by Kevin Hill, Duke University:
Study Protocol  [PDF] April 24, 2017

Additional Information:
Publications:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Kevin Hill, Associate Professor of Pediatrics, Duke University
ClinicalTrials.gov Identifier: NCT03229538    
Other Study ID Numbers: Pro00078106
1U01TR001803-01 ( U.S. NIH Grant/Contract )
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: July 17, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The investigators will disseminate findings through publications, national presentations, participation in the CTSA Consortium, the CTSA website and via the existing infrastructure of the Society of Thoracic Surgeons Congenital Heart Surgery Database. Data collection supported by CTSA funds will follow the principles outlined in the Final NIH Statement on Sharing Research Data. Participating institutions will honor the principle that data sharing is critical for expeditious translation of research findings to the improvement of human health. The investigators abide strictly by the provisions of the Health Insurance Portability and Accountability Act (HIPAA). The investigators will continue to use traditional venues for data sharing, such as publications in leading scientific journals and deposit all applicable NIH-funded research results to PubMed Central in compliance with the NIH's Public Access Policy.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Heart Diseases
Inflammation
Pathologic Processes
Cardiovascular Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents