Cardiopulmonary Bypass Induced Lipid PeroxidationNCT01366976
Inhibition of Lipid Peroxidation During Cardiac Surgery
A study testing Acetaminophen in people with Cardiopulmonary Bypass Induced Lipid Peroxidation, run by Vanderbilt University at 1 site in United States.
Trial summary
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cardiopulmonary Bypass Induced Lipid Peroxidation
- What is being tested?
- Acetaminophen
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 67 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2011to Jun 2013
- Phase
- Interventional
- 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 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
- For female subjects, the following conditions must be met:
- postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and a negative urine beta-hcg prior to drug treatment
Who cannot join
- Allergic reaction to ApAP (acetaminophen)
- Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
- Impaired renal function (serum creatinine >2.0 mg/dl)
- Emergency surgery
- Pregnancy
- Breast-feeding
Show all 12Show fewer
- Any underlying or acute disease requiring regular medication which could possibly pose a threat to the subject or make implementation of the protocol or interpretation of the study results difficult
- History of alcohol or drug abuse
- Treatment with any investigational drug in the 1 month preceding the study
- Mental conditions rendering the subject unable to understand the nature, scope and possible consequences of the study
- Inability to comply with the protocol, e.g. uncooperative attitude and unlikelihood of completing the study
- History or evidence of active asthma
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
Official title: Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Free plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute kidney injury that results from CPB. When these hemeproteins are released into the plasma, they undergo redox cycling, generating radical species that initiate lipid peroxidation and a cascade of oxidative damage to cellular membranes, notably in the kidney. F2-isoprostanes and isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased after CPB, particularly in those patients with acute kidney injury. Acetaminophen inhibits the lipid peroxidation 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. The current proposal tests the central hypothesis that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and rhabdomyolysis that occur in patients undergoing CPB. Demonstration that acetaminophen inhibits the lipid peroxidation resulting from CPB would provide a rationale for a prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute kidney injury that results from CPB.
- Being tested
- Acetaminophen
- Keywords
- oxidative stress, cardiopulmonary bypass, acetaminophen, hemolysis
- Medical subject headings
- Hemolysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AcetaminophenDrug
Also called Tylenol
Acetaminophen 1g every 6 hours for 4 doses over 24 hours
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Not described Receives: Drug: Acetaminophen |
| Acetaminophen | Active comparator | Acetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period Receives: Drug: Acetaminophen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Plasma Isofuran Concentrations
Plasma isofuran concentrations as a measure of lipid peroxidation
Measured: 24 hours
Plasma F2-isoprostane Concentrations
Plasma F2-isoprostane concentrations as a measure of lipid peroxidation
Measured: 24 hours
Secondary outcomes (2)
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)
Changes in urinary NGAL (neutrophil gelatinase-associated lipocalin) as marker of acute kidney injury
Measured: 24 hours
Serum Creatinine
Serum creatinine measured over a 72 hour period
Measured: 72 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2011 (estimated)
- Study startJul 2011
- Primary completionJun 2013
- Study completionJun 2013
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.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Cardiopulmonary Bypass Induced Lipid PeroxidationStudies of the same condition, open and under way.
- 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
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 67 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mias Pretorius, Vanderbilt University
- Investigators
- Mias Pretorius, MBChB, MSCI, Principal investigator, Vanderbilt University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01366976
- Sponsor's protocol ID
- 110423
- Status last verified
- Jan 2015
- First submitted
- 2 Jun 2011
- Last updated
- 27 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Billings FT 4th, Ball SK, Roberts LJ 2nd, Pretorius M. Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response. Free Radic Biol Med. 2011 Jun 1;50(11):1480-7. doi: 10.1016/j.freeradbiomed.2011.02.011. Epub 2011 Feb 18.
PubMed 21334433Boutaud 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 20133658Billings FT 4th, Petracek MR, Roberts LJ 2nd, Pretorius M. Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial. PLoS One. 2015 Feb 23;10(2):e0117625. doi: 10.1371/journal.pone.0117625. eCollection 2015.
PubMed 25705899
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Inhibition of Lipid Peroxidation During Cardiopulmonary Bypass
- ClinicalTrials.gov ID
- NCT01366976
- Acronym / sponsor ID
- 110423
- Keywords
- oxidative stress, cardiopulmonary bypass, acetaminophen, hemolysis
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 67 participants (actual)
- Lead sponsor
- Vanderbilt UniversityUniversity, hospital or other
- Study start
- Jul 2011
- Primary completion
- Jun 2013 (actual)
- Study completion
- Jun 2013 (actual)
- First posted
- 6 Jun 2011 (estimated)
- Results
- Posted 14 Jan 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Acute kidney injury is a major complication of cardiac surgery requiring cardiopulmonary bypass (CPB). Hemolysis and rhabdomyolysis frequently occur during CPB. Hemolysis leads to an increase in free hemoglobin, whereas rhabdomyolysis leads to an increase in myoglobin. Free plasma hemoglobin and myoglobin have been shown to be independent predictors of the acute kidney injury that results from CPB. When these hemeproteins are released into the plasma, they undergo redox cycling, generating radical species that initiate lipid peroxidation and a cascade of oxidative damage to cellular membranes, notably in the kidney. F2-isoprostanes and isofurans are sensitive and specific markers of oxidative stress in vivo, and are increased after CPB, particularly in those patients with acute kidney injury. Acetaminophen inhibits the lipid peroxidation 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. The current proposal tests the central hypothesis that acetaminophen will attenuate the lipid peroxidation associated with the hemolysis and rhabdomyolysis that occur in patients undergoing CPB. Demonstration that acetaminophen inhibits the lipid peroxidation resulting from CPB would provide a rationale for a prospective randomized trial to test the hypothesis that acetaminophen will reduce the acute kidney injury that results from CPB.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: Acetaminophen |
| Acetaminophen | Active comparator | Drug: AcetaminophenAcetaminophen will ge given as 1g every 6 hours for 4 doses over a 24 hours study period |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subjects, 18 to 80 years of age, scheduled for elective cardiac surgery requiring CPB
- For female subjects, the following conditions must be met:
- postmenopausal for at least 1 year, or status-post surgical sterilization, or if of childbearing potential, utilizing adequate birth control and a negative urine beta-hcg prior to drug treatment
Key exclusion criteria (12 listed)
- Allergic reaction to ApAP (acetaminophen)
- Evidence of severe hepatic impairment (history of liver cirrhosis or total bilirubin >2.0mg/dl)
- Impaired renal function (serum creatinine >2.0 mg/dl)
- Emergency surgery
- Pregnancy
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 1g every 6 hours for 4 doses over 24 hours | Drug | Acetaminophen, Placebo |
Primary outcome
Plasma Isofuran Concentrations
Time frame: 24 hours
Plasma isofuran concentrations as a measure of lipid peroxidation
Plasma F2-isoprostane Concentrations
Time frame: 24 hours
Plasma F2-isoprostane concentrations as a measure of lipid peroxidation
2 secondary outcomes
Urinary NGAL (Neutrophil Gelatinase-associated Lipocalin)
Time frame: 24 hours
Serum Creatinine
Time frame: 72 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 21334433Billings FT 4th, Ball SK, Roberts LJ 2nd, Pretorius M. Postoperative acute kidney injury is associated with hemoglobinemia and an enhanced oxidative stress response. Free Radic Biol Med. 2011 Jun 1;50(11):1480-7. doi: 10.1016/j.freeradbiomed.2011.02.011. Epub 2011 Feb 18.
- 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.
- Derived from this study: PubMed 25705899Billings FT 4th, Petracek MR, Roberts LJ 2nd, Pretorius M. Perioperative intravenous acetaminophen attenuates lipid peroxidation in adults undergoing cardiopulmonary bypass: a randomized clinical trial. PLoS One. 2015 Feb 23;10(2):e0117625. doi: 10.1371/journal.pone.0117625. eCollection 2015.
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.
Mias Pretorius, MBChB, MSCI 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 Cardiopulmonary Bypass Induced Lipid Peroxidation, run by Vanderbilt University 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?
The sponsor lists 3 inclusion and 12 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 27 Jan 2015. 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?
Yes. Results are posted in the registry (first posted 14 Jan 2015). 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?
Plasma Isofuran Concentrations (time frame: 24 hours). The study lists 2 primary outcomes in all. 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 NCT01366976, which also lists 3 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 27 Jan 2015; AzTrials last refreshed its copy on 7 Nov 2026.