Congenital Heart DiseaseNCT01228305
Acetaminophen for Oxidative Stress After Cardiopulmonary Bypass
A study testing Acetaminophen in people with Congenital Heart Disease and Cardiopulmonary Bypass, run by Vanderbilt University Medical Center at 1 site in United States.
Trial summary
The current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with cardiopulmonary bypass (CPB)-induced hemolysis in children undergoing cardiac surgery. Read more about this study
- Who is it for?
- Ages 1 day to 17 years
- Conditions the study is for
- Congenital Heart Disease, Cardiopulmonary Bypass
- What is being tested?
- Acetaminophen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Mar 2014
- Phase
- Interventional
- 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
Patients will be eligible for enrollment based on the following inclusion criteria:
- Infants or children (newborn to 17years of age) undergoing cardiopulmonary bypass for biventricular surgical correction of their congenital heart lesions.
Patients will not be eligible for this study based on the following exclusion criteria:
- Patients scheduled for single ventricle palliation will be excluded, in an effort to standardize the time of repair, time on CPB, and surgical procedure.
- Patients with severe neurological abnormalities at baseline.
- Patients with major non-cardiac congenital malformations, developmental disorders or serious chronic disorders. Benign congenital malformations (such as club foot, ear tags, etc.) will not exclude the subject from the study.
- Non-English speaking patients, or parent/legal guardians.
- Patients less than 3 kg, to limit risk of excessive blood loss from lab draws.
- Previous adverse reaction to acetaminophen
- History of acute or chronic kidney disease
- History of chronic liver disease
- Emergency surgery
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Does Preoperative Acetaminophen Reduce Biochemical Markers of Oxidative Stress From Cardiopulmonary Bypass?
The current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with cardiopulmonary bypass (CPB)-induced hemolysis in children undergoing cardiac surgery.
Read the detailed description
Infants with complex congenital cardiac defects frequently undergo cardiopulmonary bypass (CBP) during surgical repair of their cardiac lesions (1). CBP exposes infants and children to endothelial damage, hyperoxia, hemolysis, and systemic inflammatory response (2-7). The systemic inflammatory response contributes to the organ dysfunction and is initiated by exposure of blood to the artificial surfaces of the extracorporeal circuit resulting in significant hemolysis and activation of complement. Hyperoxia has been shown to cause oxidative stress and the production of free radical molecules, which contributes to the morbidity of CPB. Hemolysis leads to free hemoglobin and the subsequent release of free iron in the plasma, which can catalyze redox reactions and has been shown to be another source of severe oxidant injury in children following bypass (8, 9). Additionally, the release of proinflammatory cytokines, hypothermia, hemorrhage requiring multiple transfusions, and activation of neutrophils leading to an enhancement of the respiratory burst contribute to oxidative injury and worsening inflammation (9).
Myoglobin and hemoglobin contain ferrous iron (Fe2+), which normally transports reversibly bound oxygen molecules to tissues. When muscle or red blood cells are damaged, the iron-chelating heme molecules are released into the plasma, and the ferrous iron is oxidized to the ferric (Fe3+) state. In the higher oxidation state, the ferric hemoproteins are able to reduce other molecules, notably hydrogen peroxide and lipid hydroperoxides, producing lipid peroxides and ferryl (Fe4+) hemoproteins. The ferryl hemoproteins can then enter an oxidation-reduction cycle with lipid molecules, causing further lipid peroxide production, leading to a cascade of oxidative damage to cellular membranes (10-12).
With increasing oxidative stress, oxygen free radicals attack esterified arachidonate layered within cell membrane lipid bilayers, resulting in the production of multiple lipid peroxidation products called isoprostanes (Iso-P) and isofurans (IsoF) (13-17). Many forms of IsoF and IsoP have been shown to be powerful vasoconstrictors, and have been shown to contribute to the pathogenesis and organ dysfunction associated with rhabdomyolysis, subarachnoid hemorrhage and hemolytic disorders (10, 16, 18-21). F2-isoprostanes are sensitive and specific markers of oxidative stress in vivo. (4) The mechanism/s causing increased oxidative stress during CPB are incompletely understood and the relationship between free hemoglobin and F2-isoprostanes in humans undergoing CPB is unknown.
Inhibition of hemoprotein-induced oxidative stress may have important clinical applications in humans. Hemolysis, in addition to contributing to the oxidative stress response, is also associated with acute kidney injury (AKI) in patients undergoing CPB or extracorporeal life support (5-6). In fact, plasma free hemoglobin has been shown to be an independent predictor of AKI in the early postoperative period (5). We have recently demonstrated that acetaminophen, through inhibition of prostaglandin H2-synthases (PGHS), inhibits the oxidation of free arachidonic acid catalyzed by myoglobin and hemoglobin. Moreover, in an animal model of rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in creatinine clearance compared to control (10).
The current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with CPB-induced hemolysis in children undergoing cardiac surgery. If acetaminophen attenuates the oxidative stress response associated with CPB-induced hemolysis the potential therapeutic benefit extends to all cardiac surgery patients requiring CPB. Based on the outcome of this pilot study we will design a prospective randomized trial to test the hypothesis that acetaminophen will reduce AKI associated with hemoprotein-induced oxidative stress following CPB.
- Conditions
- Congenital Heart Disease, Cardiopulmonary Bypass
- Being tested
- Acetaminophen
- Keywords
- ventricular septal defect, atrioventricular septal defect, oxidative stress, cardiopulmonary bypass, acetaminophen, hemolysis, acute kidney injury, Congenital heart disease undergoing cardiopulmonary bypass
- Medical subject headings
- Heart Defects, Congenital, Heart Septal Defects, Ventricular, Atrioventricular Septal Defect, Hemolysis, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenOther
Also called Tylenol
Acetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB.
| Study group | Role | What they receive |
|---|---|---|
| Acetaminophen | Experimental | Subjects will be randomly assigned to treatment using a permuted-block randomization algorithm. Acetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB. Receives: Other: Acetaminophen |
| Placebo | Placebo comparator | Subjects will be randomly assigned to treatment using a permuted-block randomization algorithm. Acetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB. Receives: Other: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
oxidative stress response as measured by F2-isoprostane
Test the hypothesis that acetaminophen attenuates the oxidative stress response, as measured by F2-isoprostanes, in children undergoing cardiopulmonary bypass. The primary outcome is the oxidative stress response as measured by F2-isoprostane
Measured: 24 hours after cardiopulmonary bypass
Secondary outcomes (1)
renal function
Because free hemoglobin (hemolysis) has been associated with acute kidney injury (AKI) we will assess renal function as a secondary outcome in the immediate postoperative period. To assess renal function we will collect already available data including urine output, blood urea nitrogen, Creatinine and daily fluid ins and outs. Other potential confounders of AKI including cardiopulmonary bypass (CPB) time, daily use vasopressors and re-exploration for bleeding will be collected. In addition we will also measure urine neutrophil gelatinase-associated lipocalin (NGAL) as an early marker for AKI.
Measured: for the first 24 hrs after cardiopulmonary bypass
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Oct 2010 (estimated)
- Study startJul 2011
- Primary completionJan 2014
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (21)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe 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 N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Scott A Simpson, MD, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01228305
- Sponsor's protocol ID
- 090497
- Status last verified
- Apr 2017
- First submitted
- 22 Oct 2010
- Last updated
- 21 Apr 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Allen BS, Ilbawi MN. Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery. Perfusion. 2001 Mar;16 Suppl:19-29. doi: 10.1177/026765910101600i104.
PubMed 11334203Morita K, Ihnken K, Buckberg GD, Sherman MP, Young HH, Ignarro LJ. Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts. J Clin Invest. 1994 Jun;93(6):2658-66. doi: 10.1172/JCI117279.
PubMed 8201004Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R. Cardiopulmonary bypass-associated acute kidney injury: a pigment nephropathy? Contrib Nephrol. 2007;156:340-53. doi: 10.1159/000102125.
PubMed 17464145Morrow JD. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86. doi: 10.1161/01.ATV.0000152605.64964.c0. Epub 2004 Dec 9.
PubMed 15591226Vermeulen Windsant IC, Snoeijs MG, Hanssen SJ, Altintas S, Heijmans JH, Koeppel TA, Schurink GW, Buurman WA, Jacobs MJ. Hemolysis is associated with acute kidney injury during major aortic surgery. Kidney Int. 2010 May;77(10):913-20. doi: 10.1038/ki.2010.24. Epub 2010 Feb 24.
PubMed 20182411Gbadegesin R, Zhao S, Charpie J, Brophy PD, Smoyer WE, Lin JJ. Significance of hemolysis on extracorporeal life support after cardiac surgery in children. Pediatr Nephrol. 2009 Mar;24(3):589-95. doi: 10.1007/s00467-008-1047-z. Epub 2008 Nov 12.
PubMed 19002722Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brot N, Fitzgerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ 2nd, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC. Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med. 2005 Mar 15;38(6):698-710. doi: 10.1016/j.freeradbiomed.2004.09.017.
PubMed 15721980Christen S, Finckh B, Lykkesfeldt J, Gessler P, Frese-Schaper M, Nielsen P, Schmid ER, Schmitt B. Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation. Free Radic Biol Med. 2005 May 15;38(10):1323-32. doi: 10.1016/j.freeradbiomed.2005.01.016.
PubMed 15855050Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002 Jul;97(1):215-52. doi: 10.1097/00000542-200207000-00030. No abstract available.
PubMed 12131125Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, Carney CK, Masterson TS, Amin T, Wright DW, Wilson MT, Oates JA, Roberts LJ 2nd. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2699-704. doi: 10.1073/pnas.0910174107. Epub 2010 Feb 1.
PubMed 20133658Ouellet M, Percival MD. Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Arch Biochem Biophys. 2001 Mar 15;387(2):273-80. doi: 10.1006/abbi.2000.2232.
PubMed 11370851Patel RP, Svistunenko DA, Darley-Usmar VM, Symons MC, Wilson MT. Redox cycling of human methaemoglobin by H2O2 yields persistent ferryl iron and protein based radicals. Free Radic Res. 1996 Aug;25(2):117-23. doi: 10.3109/10715769609149916.
PubMed 8885329Morrow JD, Hill KE, Burk RF, Nammour TM, Badr KF, Roberts LJ 2nd. A series of prostaglandin F2-like compounds are produced in vivo in humans by a non-cyclooxygenase, free radical-catalyzed mechanism. Proc Natl Acad Sci U S A. 1990 Dec;87(23):9383-7. doi: 10.1073/pnas.87.23.9383.
PubMed 2123555Montuschi P, Barnes PJ, Roberts LJ 2nd. Isoprostanes: markers and mediators of oxidative stress. FASEB J. 2004 Dec;18(15):1791-800. doi: 10.1096/fj.04-2330rev.
PubMed 15576482Milne GL, Musiek ES, Morrow JD. F2-isoprostanes as markers of oxidative stress in vivo: an overview. Biomarkers. 2005 Nov;10 Suppl 1:S10-23. doi: 10.1080/13547500500216546.
PubMed 16298907
Study at a glance
From the registry record, last updated by the sponsor on 21 Apr 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Does Preoperative Acetaminophen Reduce Biochemical Markers of Oxidative Stress From Cardiopulmonary Bypass?
- ClinicalTrials.gov ID
- NCT01228305
- Acronym / sponsor ID
- 090497
- Conditions
- Congenital Heart Disease, Cardiopulmonary Bypass
- Keywords
- ventricular septal defect, atrioventricular septal defect, oxidative stress, cardiopulmonary bypass, acetaminophen, hemolysis, acute kidney injury, Congenital heart disease undergoing cardiopulmonary bypass
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Jan 2014 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 26 Oct 2010 (estimated)
- 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 current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with cardiopulmonary bypass (CPB)-induced hemolysis in children undergoing cardiac surgery.
Detailed description
Infants with complex congenital cardiac defects frequently undergo cardiopulmonary bypass (CBP) during surgical repair of their cardiac lesions (1). CBP exposes infants and children to endothelial damage, hyperoxia, hemolysis, and systemic inflammatory response (2-7). The systemic inflammatory response contributes to the organ dysfunction and is initiated by exposure of blood to the artificial surfaces of the extracorporeal circuit resulting in significant hemolysis and activation of complement. Hyperoxia has been shown to cause oxidative stress and the production of free radical molecules, which contributes to the morbidity of CPB. Hemolysis leads to free hemoglobin and the subsequent release of free iron in the plasma, which can catalyze redox reactions and has been shown to be another source of severe oxidant injury in children following bypass (8, 9). Additionally, the release of proinflammatory cytokines, hypothermia, hemorrhage requiring multiple transfusions, and activation of neutrophils leading to an enhancement of the respiratory burst contribute to oxidative injury and worsening inflammation (9).
Myoglobin and hemoglobin contain ferrous iron (Fe2+), which normally transports reversibly bound oxygen molecules to tissues. When muscle or red blood cells are damaged, the iron-chelating heme molecules are released into the plasma, and the ferrous iron is oxidized to the ferric (Fe3+) state. In the higher oxidation state, the ferric hemoproteins are able to reduce other molecules, notably hydrogen peroxide and lipid hydroperoxides, producing lipid peroxides and ferryl (Fe4+) hemoproteins. The ferryl hemoproteins can then enter an oxidation-reduction cycle with lipid molecules, causing further lipid peroxide production, leading to a cascade of oxidative damage to cellular membranes (10-12).
With increasing oxidative stress, oxygen free radicals attack esterified arachidonate layered within cell membrane lipid bilayers, resulting in the production of multiple lipid peroxidation products called isoprostanes (Iso-P) and isofurans (IsoF) (13-17). Many forms of IsoF and IsoP have been shown to be powerful vasoconstrictors, and have been shown to contribute to the pathogenesis and organ dysfunction associated with rhabdomyolysis, subarachnoid hemorrhage and hemolytic disorders (10, 16, 18-21). F2-isoprostanes are sensitive and specific markers of oxidative stress in vivo. (4) The mechanism/s causing increased oxidative stress during CPB are incompletely understood and the relationship between free hemoglobin and F2-isoprostanes in humans undergoing CPB is unknown.
Inhibition of hemoprotein-induced oxidative stress may have important clinical applications in humans. Hemolysis, in addition to contributing to the oxidative stress response, is also associated with acute kidney injury (AKI) in patients undergoing CPB or extracorporeal life support (5-6). In fact, plasma free hemoglobin has been shown to be an independent predictor of AKI in the early postoperative period (5). We have recently demonstrated that acetaminophen, through inhibition of prostaglandin H2-synthases (PGHS), inhibits the oxidation of free arachidonic acid catalyzed by myoglobin and hemoglobin. Moreover, in an animal model of rhabdomyolysis-induced kidney injury, acetaminophen significantly attenuated the decrease in creatinine clearance compared to control (10).
The current proposal tests the central hypothesis that acetaminophen will attenuate the oxidative stress response associated with CPB-induced hemolysis in children undergoing cardiac surgery. If acetaminophen attenuates the oxidative stress response associated with CPB-induced hemolysis the potential therapeutic benefit extends to all cardiac surgery patients requiring CPB. Based on the outcome of this pilot study we will design a prospective randomized trial to test the hypothesis that acetaminophen will reduce AKI associated with hemoprotein-induced oxidative stress following CPB.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Acetaminophen | Experimental | Other: AcetaminophenSubjects will be randomly assigned to treatment using a permuted-block randomization algorithm. Acetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB. |
| Placebo | Placebo comparator | Other: AcetaminophenSubjects will be randomly assigned to treatment using a permuted-block randomization algorithm. Acetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB. |
Who may qualify
- Ages
- 1 day to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
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 |
|---|---|---|
| AcetaminophenAlso: TylenolAcetaminophen will be given at a standard dose of 15 mg/kg IV every 6 hours for children >=2 years of age, 12.5mg/kg IV every 6 hours for children 29 days to <2 years of age, and 7.5mg/kg IV every 6 hours for neonates up to 28 days old for a total of 4 doses, starting shortly after intubation in the OR and before the start of CPB. | Other | Acetaminophen, Placebo |
Primary outcome
oxidative stress response as measured by F2-isoprostane
Time frame: 24 hours after cardiopulmonary bypass
Test the hypothesis that acetaminophen attenuates the oxidative stress response, as measured by F2-isoprostanes, in children undergoing cardiopulmonary bypass. The primary outcome is the oxidative stress response as measured by F2-isoprostane
1 secondary outcome
renal function
Time frame: for the first 24 hrs after cardiopulmonary bypass
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 21 Apr 2017.
- Background: PubMed 11334203Allen BS, Ilbawi MN. Hypoxia, reoxygenation and the role of systemic leukodepletion in pediatric heart surgery. Perfusion. 2001 Mar;16 Suppl:19-29. doi: 10.1177/026765910101600i104.
- Background: PubMed 8201004Morita K, Ihnken K, Buckberg GD, Sherman MP, Young HH, Ignarro LJ. Role of controlled cardiac reoxygenation in reducing nitric oxide production and cardiac oxidant damage in cyanotic infantile hearts. J Clin Invest. 1994 Jun;93(6):2658-66. doi: 10.1172/JCI117279.
- Background: PubMed 17464145Haase M, Haase-Fielitz A, Bagshaw SM, Ronco C, Bellomo R. Cardiopulmonary bypass-associated acute kidney injury: a pigment nephropathy? Contrib Nephrol. 2007;156:340-53. doi: 10.1159/000102125.
- Background: PubMed 15591226Morrow JD. Quantification of isoprostanes as indices of oxidant stress and the risk of atherosclerosis in humans. Arterioscler Thromb Vasc Biol. 2005 Feb;25(2):279-86. doi: 10.1161/01.ATV.0000152605.64964.c0. Epub 2004 Dec 9.
- Background: PubMed 20182411Vermeulen Windsant IC, Snoeijs MG, Hanssen SJ, Altintas S, Heijmans JH, Koeppel TA, Schurink GW, Buurman WA, Jacobs MJ. Hemolysis is associated with acute kidney injury during major aortic surgery. Kidney Int. 2010 May;77(10):913-20. doi: 10.1038/ki.2010.24. Epub 2010 Feb 24.
- Background: PubMed 19002722Gbadegesin R, Zhao S, Charpie J, Brophy PD, Smoyer WE, Lin JJ. Significance of hemolysis on extracorporeal life support after cardiac surgery in children. Pediatr Nephrol. 2009 Mar;24(3):589-95. doi: 10.1007/s00467-008-1047-z. Epub 2008 Nov 12.
- Background: PubMed 15721980Kadiiska MB, Gladen BC, Baird DD, Germolec D, Graham LB, Parker CE, Nyska A, Wachsman JT, Ames BN, Basu S, Brot N, Fitzgerald GA, Floyd RA, George M, Heinecke JW, Hatch GE, Hensley K, Lawson JA, Marnett LJ, Morrow JD, Murray DM, Plastaras J, Roberts LJ 2nd, Rokach J, Shigenaga MK, Sohal RS, Sun J, Tice RR, Van Thiel DH, Wellner D, Walter PB, Tomer KB, Mason RP, Barrett JC. Biomarkers of oxidative stress study II: are oxidation products of lipids, proteins, and DNA markers of CCl4 poisoning? Free Radic Biol Med. 2005 Mar 15;38(6):698-710. doi: 10.1016/j.freeradbiomed.2004.09.017.
- Background: PubMed 15855050Christen S, Finckh B, Lykkesfeldt J, Gessler P, Frese-Schaper M, Nielsen P, Schmid ER, Schmitt B. Oxidative stress precedes peak systemic inflammatory response in pediatric patients undergoing cardiopulmonary bypass operation. Free Radic Biol Med. 2005 May 15;38(10):1323-32. doi: 10.1016/j.freeradbiomed.2005.01.016.
- Background: PubMed 12131125Laffey JG, Boylan JF, Cheng DC. The systemic inflammatory response to cardiac surgery: implications for the anesthesiologist. Anesthesiology. 2002 Jul;97(1):215-52. doi: 10.1097/00000542-200207000-00030. No abstract available.
- Background: PubMed 20133658Boutaud O, Moore KP, Reeder BJ, Harry D, Howie AJ, Wang S, Carney CK, Masterson TS, Amin T, Wright DW, Wilson MT, Oates JA, Roberts LJ 2nd. Acetaminophen inhibits hemoprotein-catalyzed lipid peroxidation and attenuates rhabdomyolysis-induced renal failure. Proc Natl Acad Sci U S A. 2010 Feb 9;107(6):2699-704. doi: 10.1073/pnas.0910174107. Epub 2010 Feb 1.
- Background: PubMed 11370851Ouellet M, Percival MD. Mechanism of acetaminophen inhibition of cyclooxygenase isoforms. Arch Biochem Biophys. 2001 Mar 15;387(2):273-80. doi: 10.1006/abbi.2000.2232.
- Background: PubMed 8885329Patel RP, Svistunenko DA, Darley-Usmar VM, Symons MC, Wilson MT. Redox cycling of human methaemoglobin by H2O2 yields persistent ferryl iron and protein based radicals. Free Radic Res. 1996 Aug;25(2):117-23. doi: 10.3109/10715769609149916.
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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.
Scott A Simpson, MD principal investigator
Vanderbilt University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Acetaminophen in people with Congenital Heart Disease and Cardiopulmonary Bypass, run by Vanderbilt University Medical Center at 1 site 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?
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 21 Apr 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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?
oxidative stress response as measured by F2-isoprostane (time frame: 24 hours after cardiopulmonary bypass). 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 NCT01228305, which also lists 21 linked publications.
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 21 Apr 2017.