Inflammatory Response Clinical Trial
— STRESSOfficial title:
STeroids to REduce Systemic Inflammation After Infant Heart Surgery (STRESS)
Verified date | May 2023 |
Source | Duke University |
Contact | n/a |
Is FDA regulated | No |
Health authority | |
Study type | Interventional |
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.
Status | Completed |
Enrollment | 1263 |
Est. completion date | March 31, 2022 |
Est. primary completion date | March 31, 2022 |
Accepts healthy volunteers | No |
Gender | All |
Age group | N/A to 12 Months |
Eligibility | 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 |
Country | Name | City | State |
---|---|---|---|
United States | University of Colorado, Denver | Aurora | Colorado |
United States | Johns Hopkins University | Baltimore | Maryland |
United States | Medical University of South Carolina | Charleston | South Carolina |
United States | Ann & Robert Lurie Children's Hospital of Chicago | Chicago | Illinois |
United States | Children's Hospital Medical Center | Cincinnati | Ohio |
United States | Cleveland Clinic | Cleveland | Ohio |
United States | Nationwide Children's Hospital | Columbus | Ohio |
United States | The University of Texas Southwestern Medical Center | Dallas | Texas |
United States | Duke University Medical Center | Durham | North Carolina |
United States | University of Florida Health - Shands Hospital | Gainesville | Florida |
United States | Baylor College of Medicine, Texas Children's Hospital | Houston | Texas |
United States | Children's Mercy Hospital | Kansas City | Missouri |
United States | Children's Hospital of Los Angeles | Los Angeles | California |
United States | Medical College of Wisconsin | Milwaukee | Wisconsin |
United States | Children's Hospital and Clinics of Minnesota | Minneapolis | Minnesota |
United States | Vanderbilt University Medical Center | Nashville | Tennessee |
United States | Morgan Stanley Children's Hospital of New York Presbyterian | New York | New York |
United States | Advocate Children's Hospital | Oak Lawn | Illinois |
United States | Children's Hospital and Medical Center | Omaha | Nebraska |
United States | Children's Hospital of Pittsburgh | Pittsburgh | Pennsylvania |
United States | University of Rochester Medical Center | Rochester | New York |
United States | St. Louis Children's Hospital | Saint Louis | Missouri |
United States | Utah/Primary Children's Medical Center | Salt Lake City | Utah |
Lead Sponsor | Collaborator |
---|---|
Kevin Hill | National Center for Advancing Translational Sciences (NCATS) |
United States,
Ando M, Park IS, Wada N, Takahashi Y. Steroid supplementation: a legitimate pharmacotherapy after neonatal open heart surgery. Ann Thorac Surg. 2005 Nov;80(5):1672-8; discusison 1678. doi: 10.1016/j.athoracsur.2005.04.035. — View Citation
Bronicki RA, Backer CL, Baden HP, Mavroudis C, Crawford SE, Green TP. Dexamethasone reduces the inflammatory response to cardiopulmonary bypass in children. Ann Thorac Surg. 2000 May;69(5):1490-5. doi: 10.1016/s0003-4975(00)01082-1. — View Citation
Checchia PA, Backer CL, Bronicki RA, Baden HP, Crawford SE, Green TP, Mavroudis C. Dexamethasone reduces postoperative troponin levels in children undergoing cardiopulmonary bypass. Crit Care Med. 2003 Jun;31(6):1742-5. doi: 10.1097/01.CCM.0000063443.32874.60. — View Citation
Clarizia NA, Manlhiot C, Schwartz SM, Sivarajan VB, Maratta R, Holtby HM, Gruenwald CE, Caldarone CA, Van Arsdell GS, McCrindle BW. Improved outcomes associated with intraoperative steroid use in high-risk pediatric cardiac surgery. Ann Thorac Surg. 2011 Apr;91(4):1222-7. doi: 10.1016/j.athoracsur.2010.11.005. — View Citation
Garg AX, Vincent J, Cuerden M, Parikh C, Devereaux PJ, Teoh K, Yusuf S, Hildebrand A, Lamy A, Zuo Y, Sessler DI, Shah P, Abbasi SH, Quantz M, Yared JP, Noiseux N, Tagarakis G, Rochon A, Pogue J, Walsh M, Chan MT, Lamontagne F, Salehiomran A, Whitlock R; SIRS Investigators. Steroids In caRdiac Surgery (SIRS) trial: acute kidney injury substudy protocol of an international randomised controlled trial. BMJ Open. 2014 Mar 5;4(3):e004842. doi: 10.1136/bmjopen-2014-004842. — View Citation
Graham EM, Atz AM, Butts RJ, Baker NL, Zyblewski SC, Deardorff RL, DeSantis SM, Reeves ST, Bradley SM, Spinale FG. Standardized preoperative corticosteroid treatment in neonates undergoing cardiac surgery: results from a randomized trial. J Thorac Cardiovasc Surg. 2011 Dec;142(6):1523-9. doi: 10.1016/j.jtcvs.2011.04.019. Epub 2011 May 20. — View Citation
Graham EM, Atz AM, McHugh KE, Butts RJ, Baker NL, Stroud RE, Reeves ST, Bradley SM, McGowan FX Jr, Spinale FG. Preoperative steroid treatment does not improve markers of inflammation after cardiac surgery in neonates: results from a randomized trial. J Thorac Cardiovasc Surg. 2014 Mar;147(3):902-8. doi: 10.1016/j.jtcvs.2013.06.010. Epub 2013 Jul 16. — View Citation
Graham EM. The utility of steroids in pediatric cardiac operations*. Pediatr Crit Care Med. 2014 Jun;15(5):492-3. doi: 10.1097/PCC.0000000000000139. No abstract available. — View Citation
Hoffman TM, Wernovsky G, Atz AM, Kulik TJ, Nelson DP, Chang AC, Bailey JM, Akbary A, Kocsis JF, Kaczmarek R, Spray TL, Wessel DL. Efficacy and safety of milrinone in preventing low cardiac output syndrome in infants and children after corrective surgery for congenital heart disease. Circulation. 2003 Feb 25;107(7):996-1002. doi: 10.1161/01.cir.0000051365.81920.28. — View Citation
Jacobs ML, O'Brien SM, Jacobs JP, Mavroudis C, Lacour-Gayet F, Pasquali SK, Welke K, Pizarro C, Tsai F, Clarke DR. An empirically based tool for analyzing morbidity associated with operations for congenital heart disease. J Thorac Cardiovasc Surg. 2013 Apr;145(4):1046-1057.e1. doi: 10.1016/j.jtcvs.2012.06.029. Epub 2012 Jul 24. — View Citation
Parr GV, Blackstone EH, Kirklin JW. Cardiac performance and mortality early after intracardiac surgery in infants and young children. Circulation. 1975 May;51(5):867-74. doi: 10.1161/01.cir.51.5.867. — View Citation
Pasquali SK, Li JS, He X, Jacobs ML, O'Brien SM, Hall M, Jaquiss RD, Welke KF, Peterson ED, Shah SS, Gaynor JW, Jacobs JP. Perioperative methylprednisolone and outcome in neonates undergoing heart surgery. Pediatrics. 2012 Feb;129(2):e385-91. doi: 10.1542/peds.2011-2034. Epub 2012 Jan 23. — View Citation
Petrini J, Damus K, Johnston RB Jr. An overview of infant mortality and birth defects in the United States. Teratology. 1997 Jul-Aug;56(1-2):8-10. doi: 10.1002/(SICI)1096-9926(199707/08)56:1/23.0.CO;2-U. No abstract available. — View Citation
Petrini J, Damus K, Russell R, Poschman K, Davidoff MJ, Mattison D. Contribution of birth defects to infant mortality in the United States. Teratology. 2002;66 Suppl 1:S3-6. doi: 10.1002/tera.90002. — View Citation
Scrascia G, Rotunno C, Guida P, Amorese L, Polieri D, Codazzi D, Paparella D. Perioperative steroids administration in pediatric cardiac surgery: a meta-analysis of randomized controlled trials*. Pediatr Crit Care Med. 2014 Jun;15(5):435-42. doi: 10.1097/PCC.0000000000000128. — View Citation
Toledo-Pereyra LH, Lin CY, Kundler H, Replogle RL. Steroids in heart surgery: a clinical double-blind and randomized study. Am Surg. 1980 Mar;46(3):155-60. — View Citation
Ungerleider RM. Practice patterns in neonatal cardiopulmonary bypass. ASAIO J. 2005 Nov-Dec;51(6):813-5. doi: 10.1097/01.mat.0000183473.93237.10. No abstract available. — View Citation
Wan S, LeClerc JL, Vincent JL. Inflammatory response to cardiopulmonary bypass: mechanisms involved and possible therapeutic strategies. Chest. 1997 Sep;112(3):676-92. doi: 10.1378/chest.112.3.676. — View Citation
Wernovsky G, Wypij D, Jonas RA, Mayer JE Jr, Hanley FL, Hickey PR, Walsh AZ, Chang AC, Castaneda AR, Newburger JW, Wessel DL. Postoperative course and hemodynamic profile after the arterial switch operation in neonates and infants. A comparison of low-flow cardiopulmonary bypass and circulatory arrest. Circulation. 1995 Oct 15;92(8):2226-35. doi: 10.1161/01.cir.92.8.2226. — View Citation
Yang Q, Chen H, Correa A, Devine O, Mathews TJ, Honein MA. Racial differences in infant mortality attributable to birth defects in the United States, 1989-2002. Birth Defects Res A Clin Mol Teratol. 2006 Oct;76(10):706-13. doi: 10.1002/bdra.20308. — View Citation
Yang Q, Khoury MJ, Mannino D. Trends and patterns of mortality associated with birth defects and genetic diseases in the United States, 1979-1992: an analysis of multiple-cause mortality data. Genet Epidemiol. 1997;14(5):493-505. doi: 10.1002/(SICI)1098-2272(1997)14:53.0.CO;2-2. — View Citation
* Note: There are 21 references in all — Click here to view all references
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Number of Participants at Each Global Rank Endpoint Based Upon Their Most-severe Outcome | 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. Rank of 91 = Post-operative length of stay > 90 days, 92 = Post-op cardiac arrest, multi-system organ failure, renal failure with temporary dialysis, or prolonged ventilator support, 93 = Reoperation for bleeding, unplanned delayed sternal closure, or post-op unplanned interventional cardiac catheterization, 94 = Post-operative mechanical circulatory support or unplanned cardiac reoperation (exclusive of reoperation for bleeding), 95 = Renal failure with permanent dialysis, neurologic deficit persistent at discharge, or respiratory failure requiring tracheostomy; 96 = Heart transplant (during hospitalization); 97 = Operative mortality. Ranks 1 through 90 correspond to the post-operative length of stay in days. | Until hospital discharge, up to 4 months | |
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 | up to 30 days | ||
Secondary | Number of Participants With Death or Major Complication as Defined by an Outcome in One of the 7 Highest Global Ranking Categories | The 7 highest global ranking categories range from 91 (postoperative length of hospital stay > 90 days) to 97 (operative mortality). | Until hospital discharge, up to 4 months | |
Secondary | Number of Participants With a Post-operative Length of Stay Greater Than 90 Days | Calculated as discharge date minus surgery date. | Until hospital discharge, up to 4 months | |
Secondary | Number of Participants With Prolonged Mechanical Ventilation (Greater Than 7 Days) | Until hospital discharge, up to 4 months | ||
Secondary | Number of Participants With Post-operative Low Cardiac Output Syndrome | Based upon the STS-CHSD registry defined "cardiac dysfunction resulting in low cardiac output" complication variable. | Until hospital discharge, up to 4 months | |
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. | Until hospital discharge, up to 4 months | ||
Secondary | Number of Participants With Any Other Post-operative Complications From the Start of Study Drug Administration Until Hospital Discharge. | Until hospital discharge, up to 4 months | ||
Secondary | PK/PD - Time to Maximum Concentration (Tmax) | 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) | ||
Secondary | PK/PD - Maximum Concentration (Cmax) | 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) | ||
Secondary | PK/PD - Clearance (CL) | 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) | ||
Secondary | PK/PD - Volume of Distribution (Vd) | 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) | ||
Secondary | Post-operative Biomarkers of the Inflammatory Response to Cardiopulmonary Bypass Including Interleukins 6 and 8 | Only to be collected at select centers and in those patients whose parent/legally authorized representative have granted consent to blood draws | 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 |
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