Disorder; Heart, Functional, Postoperative, Cardiac SurgeryPhase 4STARRNCT01780740
Statin Therapy In Atrial Refractoriness and Reperfusion Injury
A Phase 4 study testing Atorvastatin in people with Disorder; Heart, Functional, Postoperative, Cardiac Surgery and Cardiac Insufficiency Following Cardiac Surgery, run by University of Oxford at 1 site in United Kingdom.
Trial summary
Patients with coronary artery disease are often prescribed drugs called statins because research has shown that, by lowering cholesterol, they reduce the risk of having a heart attack or other complications in the long-term. Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Disorder; Heart, Functional, Postoperative, Cardiac Surgery, Cardiac Insufficiency Following Cardiac Surgery, Atrial Fibrillation
- What is being tested?
- Atorvastatin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- Jan 2012to Aug 2014
- Phase
- Phase 4
- 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 18 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Requiring elective cardiac surgery.
- Able (in the Investigators' opinion) and willing to comply with all study requirements.
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
Who cannot join
- Age>85yrs
- Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
- Women of child-bearing potential without appropriate contraceptive measures. These include oral contraceptive pills, Intrauterine contraceptive devices etc
- History of obstructive hepatobiliary disease or other serious hepatic disease or pre-operative ALT >2-fold the upper limit of normal or alcohol abuse
- Creatinine >200 umol/L
- Untreated hypothyroidism
Show all 10Show fewer
- Family history of hereditary muscle disorders
- Known intolerance to statins or history of muscle toxicity with fibrates or statins.
- Ongoing use of fibrates, niacin or of agents that are strong inhibitors of cytochrome P-450 or the P-glycoprotein within a month preceding randomization (cyclosporine, azole antifungals, such as itraconazole and ketoconazole, macrolide antibiotics, such as erythromycin and clarithromycin, protease inhibitors, nefazodone, verapamil, amiodarone or large quantity of grapefruit juice (≥ 1L/day) Patients on treatment with anti arrhythmic agents, other than beta-adrenergic receptor blockers.
- Participant who is terminally ill or is inappropriate for placebo medication.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Oxford University Hospitals NHS trust
Oxford, Oxfordshire, OX3 9DU
About this study
Official title: Prevention of Atrial Oxidative Stress and Electrical Remodelling in Patients Undergoing Cardiac Surgery: Randomised Placebo-controlled Trial of Perioperative High-dose Atorvastatin
Patients with coronary artery disease are often prescribed drugs called statins because research has shown that, by lowering cholesterol, they reduce the risk of having a heart attack or other complications in the long-term. Experimental studies have suggested that statins may also have rapid anti-inflammatory, anti-oxidant and anti arrhythmic actions; however, whether these effects are of any benefit to patients remains to be proven. The purpose of STARR trial (Statin Therapy in Atrial Refractoriness and Reperfusion injury) is to evaluate whether a short course of a commonly used statin (atorvastatin, 80 mg once a day) decreases inflammation and stabilises electrical properties of the upper chamber of the heart in the post operative period of patients undergoing cardiac surgery on the heart-lung machine either for valve replacement and/or coronary artery bypass grafting. It will also examine whether this treatment can protect the heart from sustaining tissue damage when blood supply is restored after a period of ischaemia during the course of the surgery.In addition it will also explore the impact of this intervention on biology of the vessels used for bypass surgery and the fat tissue in the vicinity of the heart \& blood vessels.
Read the detailed description
Evidence that pre- or perioperative statin treatment may reduce the occurrence of post-operative atrial fibrillation and improve clinical outcome in patients undergoing coronary artery bypass graft (CABG) or major vascular surgery has been largely generated by observational studies. In a recent meta-analysis of 6 randomized trials (of which only 2 had postoperative atrial fibrillation (AF) as a predefined outcome) evaluating the use of perioperative statin treatment in patients undergoing cardiac surgery (n=651 patients in total - study size between 40 and 200 patients), statin use was found to reduce the patients' relative risk of developing postoperative AF by 43% (RR 0.57, 95%CI 0.45,0.72) and their absolute risk by 14% (95% CI 8%,20%). Although these findings would be consistent with a rapid and, possibly, lipid-independent antiarrhythmic effect of statins, they have important limitations (e.g., single-centre, small size, lack of continuous ECG monitoring, mostly "ancillary" findings") and less bearing on current clinical practice, as they mostly included statin-naïve patients. For these reasons, the recent guidelines for the management of AF have not given a strong recommendation for the use of statins in the prevention of postoperative AF. Thus, whether intensive statin treatment in the perioperative period can confer cardio protection by reduction of atrial oxidative stress \& improvement in atrial electrical remodelling remains to be demonstrated.As endothelial function is a strong determinant of clinical outcomes, improvement of vascular redox state \& increase in nitric oxide bioavailability of arterial \& venous grafts of patients undergoing cardiac surgery may improve post operative outcomes.However it is still unclear whether higher doses of atorvastatin could confer additional beneficial effects on human vessels. Adipose tissue (AT) by releasing vasoactive molecules \& adipokines can affect myocardial and vascular biology. Recent evidence suggests that statins may favourably alter AT biosynthetic activity and increase the AT release of adiponectin (An adipokine that has been shown to have anti-inflammatory and anti-atherogenic effects) in turn improving the vascular \& myocardial redox state. However there are only limited data on the effects of statins on human adipose tissue biology and most findings to date are based on cell lines and/or relevant mouse models.
- Conditions
- Disorder; Heart, Functional, Postoperative, Cardiac Surgery, Cardiac Insufficiency Following Cardiac Surgery, Atrial Fibrillation, Ischaemia-reperfusion Injury
- Being tested
- Atorvastatin, Placebo
- Keywords
- Bypass Surgery, Coronary Artery, Atrial fibrillation, Ischaemia-reperfusion injury, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Statins, HMG-CoA
- Medical subject headings
- Atrial Fibrillation, Reperfusion Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtorvastatinDrug
Also called Lipitor
Atorvastatin (80 mg od) started not earlier than 6 days before surgery and continued until the 5th post-operative day included;
PlaceboDrug
Also called Sugar pill manufactured to mimic Atorvastatin 40mg tablet.
Placebo started not earlier than 6 days before surgery and continued until the 5th post-operative day included;
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin | Experimental | Atorvastatin (80 mg od) started not earlier than 6 days before surgery and continued until the 5th post-operative day included; Receives: Drug: Atorvastatin |
| Sugar pill | Placebo comparator | Placebo started not earlier than 6 days before surgery and continued until the 5th post-operative day included. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Post operative changes in the atrial effective refractory period
The atrial effective refractory period (ERP) will be measured daily after surgery (up to post-operative day 4) based on a programmed stimulation protocol delivered by Medtronic Pacing system analyser 2090 via a Medtronic pacemaker connected serially to the atrial epicardial pacing wires.
Measured: Serial measurements over the first 4 post operative days
Atrial tissue biomarkers
Evaluation of production of reactive oxygen species
Measured: Right atrial appendage harvested at the time of venous cannulation and after separation from cardio-pulmonary bypass
Secondary outcomes (6)
Post-operative recovery of left ventricular systolic and diastolic function
Measured: Assessed by transthoracic echocardiography before surgery as well as before the day of first hospital discharge with an average of 5 days after surgery
Atrial tissue biomarkers
Biomarkers of inflammation and oxidant stress. Evaluation of nitric oxide (NO)-redox balance and contribution of individual atrial oxidase systems.
Measured: Right atrial appendage harvested at the time of venous cannulation and after separation from cardio-pulmonary bypass
Adipose tissue biomarkers
Biomarkers of inflammation and oxidant stress. Evaluation of production of reactive oxygen species,Nitric oxide (NO)-redox balance and contribution of individual atrial oxidase systems.
Measured: Epicardial,perivascular, mesothoracic and subcutaneous adipose tissue samples collected at the time of surgery
Vascular tissue biomarkers
Biomarkers of inflammation and oxidant stress. Evaluation of production of reactive oxygen species,Nitric oxide (NO)-redox balance and contribution of individual atrial oxidase systems.
Measured: Surplus vessels from saphenous venous and internal mammary artery grafts collected at the time of surgery
Biomarkers in peripheral blood
Biomarkers of inflammation,oxidant stress and heart failure.
Measured: Peripheral blood samples processed to separate plasma/serum before surgery, on post operative day 3 and 5
Post operative atrial fibrillation detected by continuous ECG monitoring.
Measured: Monitoring will commence soon after surgery and will be continued until the end of post operative day 5
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2013 (estimated)
- Study startJan 2012
- Primary completionAug 2014
- Study completionAug 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Disorder; Heart, Functional, Postoperative, Cardiac SurgeryStudies of the same condition, open and under way.
- More trials run by University of OxfordThe 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Prof.Barbara Casadei, MD.DPhil.FRCP, Principal investigator, Department of Cardiovascular Medicine, John Radcliffe Hospital, University of OxfordDr.Raja Jayaram, MD, Principal investigator, Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01780740
- Sponsor's protocol ID
- 10/H0505/35
- Other IDs
- 2009-013228-21, 2009
- Acronym
- STARR
- Status last verified
- Aug 2014
- First submitted
- 23 Jan 2013
- Last updated
- 7 Aug 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol. 2012 Jan 3;59(1):60-70. doi: 10.1016/j.jacc.2011.08.062.
PubMed 22192670Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011 Jul 19;124(3):335-45. doi: 10.1161/CIRCULATIONAHA.110.985150. Epub 2011 Jul 5.
PubMed 21730307Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation. 2011 Sep 6;124(10):1107-17. doi: 10.1161/CIRCULATIONAHA.111.029223. Epub 2011 Aug 15.
PubMed 21844076Chen WT, Krishnan GM, Sood N, Kluger J, Coleman CI. Effect of statins on atrial fibrillation after cardiac surgery: a duration- and dose-response meta-analysis. J Thorac Cardiovasc Surg. 2010 Aug;140(2):364-72. doi: 10.1016/j.jtcvs.2010.02.042. Epub 2010 Apr 9.
PubMed 20381820European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. No abstract available.
PubMed 20802247Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol. 2008 Jan 1;51(1):68-74. doi: 10.1016/j.jacc.2007.07.085.
PubMed 18174039Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res. 2005 Sep 30;97(7):629-36. doi: 10.1161/01.RES.0000183735.09871.61. Epub 2005 Aug 25.
PubMed 16123335Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation. 2003 Sep 30;108(13):1567-74. doi: 10.1161/01.CIR.0000091084.46500.BB. Epub 2003 Sep 8.
PubMed 12963641Laufs U, Kilter H, Konkol C, Wassmann S, Bohm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res. 2002 Mar;53(4):911-20. doi: 10.1016/s0008-6363(01)00540-5.
PubMed 11922901Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation. 2010 Sep 14;122(11 Suppl):S66-73. doi: 10.1161/CIRCULATIONAHA.109.927376.
PubMed 20837928Wojcicka G, Jamroz-Wisniewska A, Atanasova P, Chaldakov GN, Chylinska-Kula B, Beltowski J. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacol Res. 2011 Jan;63(1):68-76. doi: 10.1016/j.phrs.2010.10.011. Epub 2010 Oct 20.
PubMed 20969959Jayaram R, Jones M, Reilly S, Crabtree MJ, Pal N, Goodfellow N, Nahar K, Simon J, Carnicer R, DeSilva R, Ratnatunga C, Petrou M, Sayeed R, Roalfe A, Channon KM, Bashir Y, Betts T, Hill M, Casadei B. Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin. Cardiovasc Res. 2022 Jan 7;118(1):184-195. doi: 10.1093/cvr/cvaa302.
PubMed 33098411
Study at a glance
From the registry record, last updated by the sponsor on 7 Aug 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Atrial Oxidative Stress and Electrical Remodelling in Patients Undergoing Cardiac Surgery: Randomised Placebo-controlled Trial of Perioperative High-dose Atorvastatin
- ClinicalTrials.gov ID
- NCT01780740
- Acronym / sponsor ID
- STARR / 10/H0505/35
- Conditions
- Disorder; Heart, Functional, Postoperative, Cardiac Surgery, Cardiac Insufficiency Following Cardiac Surgery, Atrial Fibrillation, Ischaemia-reperfusion Injury
- Keywords
- Bypass Surgery, Coronary Artery, Atrial fibrillation, Ischaemia-reperfusion injury, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Statins, HMG-CoA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Study start
- Jan 2012
- Primary completion
- Aug 2014 (actual)
- Study completion
- Aug 2014 (actual)
- First posted
- 31 Jan 2013 (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.
Patients with coronary artery disease are often prescribed drugs called statins because research has shown that, by lowering cholesterol, they reduce the risk of having a heart attack or other complications in the long-term. Experimental studies have suggested that statins may also have rapid anti-inflammatory, anti-oxidant and anti arrhythmic actions; however, whether these effects are of any benefit to patients remains to be proven. The purpose of STARR trial (Statin Therapy in Atrial Refractoriness and Reperfusion injury) is to evaluate whether a short course of a commonly used statin (atorvastatin, 80 mg once a day) decreases inflammation and stabilises electrical properties of the upper chamber of the heart in the post operative period of patients undergoing cardiac surgery on the heart-lung machine either for valve replacement and/or coronary artery bypass grafting. It will also examine whether this treatment can protect the heart from sustaining tissue damage when blood supply is restored after a period of ischaemia during the course of the surgery.In addition it will also explore the impact of this intervention on biology of the vessels used for bypass surgery and the fat tissue in the vicinity of the heart \& blood vessels.
Detailed description
Evidence that pre- or perioperative statin treatment may reduce the occurrence of post-operative atrial fibrillation and improve clinical outcome in patients undergoing coronary artery bypass graft (CABG) or major vascular surgery has been largely generated by observational studies. In a recent meta-analysis of 6 randomized trials (of which only 2 had postoperative atrial fibrillation (AF) as a predefined outcome) evaluating the use of perioperative statin treatment in patients undergoing cardiac surgery (n=651 patients in total - study size between 40 and 200 patients), statin use was found to reduce the patients' relative risk of developing postoperative AF by 43% (RR 0.57, 95%CI 0.45,0.72) and their absolute risk by 14% (95% CI 8%,20%). Although these findings would be consistent with a rapid and, possibly, lipid-independent antiarrhythmic effect of statins, they have important limitations (e.g., single-centre, small size, lack of continuous ECG monitoring, mostly "ancillary" findings") and less bearing on current clinical practice, as they mostly included statin-naïve patients. For these reasons, the recent guidelines for the management of AF have not given a strong recommendation for the use of statins in the prevention of postoperative AF. Thus, whether intensive statin treatment in the perioperative period can confer cardio protection by reduction of atrial oxidative stress \& improvement in atrial electrical remodelling remains to be demonstrated.As endothelial function is a strong determinant of clinical outcomes, improvement of vascular redox state \& increase in nitric oxide bioavailability of arterial \& venous grafts of patients undergoing cardiac surgery may improve post operative outcomes.However it is still unclear whether higher doses of atorvastatin could confer additional beneficial effects on human vessels. Adipose tissue (AT) by releasing vasoactive molecules \& adipokines can affect myocardial and vascular biology. Recent evidence suggests that statins may favourably alter AT biosynthetic activity and increase the AT release of adiponectin (An adipokine that has been shown to have anti-inflammatory and anti-atherogenic effects) in turn improving the vascular \& myocardial redox state. However there are only limited data on the effects of statins on human adipose tissue biology and most findings to date are based on cell lines and/or relevant mouse models.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin | Experimental | Drug: AtorvastatinAtorvastatin (80 mg od) started not earlier than 6 days before surgery and continued until the 5th post-operative day included; |
| Sugar pill | Placebo comparator | Drug: PlaceboPlacebo started not earlier than 6 days before surgery and continued until the 5th post-operative day included. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Participant is willing and able to give informed consent for participation in the study.
- Male or Female, aged 18 years or above.
- Requiring elective cardiac surgery.
- Able (in the Investigators' opinion) and willing to comply with all study requirements.
- Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
Key exclusion criteria (10 listed)
- Age>85yrs
- Female participant who is pregnant, lactating or planning pregnancy during the course of the study.
- Women of child-bearing potential without appropriate contraceptive measures. These include oral contraceptive pills, Intrauterine contraceptive devices etc
- History of obstructive hepatobiliary disease or other serious hepatic disease or pre-operative ALT >2-fold the upper limit of normal or alcohol abuse
- Creatinine >200 umol/L
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 |
|---|---|---|
| AtorvastatinAlso: LipitorAtorvastatin (80 mg od) started not earlier than 6 days before surgery and continued until the 5th post-operative day included; | Drug | Atorvastatin |
| PlaceboAlso: Sugar pill manufactured to mimic Atorvastatin 40mg tablet.Placebo started not earlier than 6 days before surgery and continued until the 5th post-operative day included; | Drug | Sugar pill |
Primary outcome
Post operative changes in the atrial effective refractory period
Time frame: Serial measurements over the first 4 post operative days
The atrial effective refractory period (ERP) will be measured daily after surgery (up to post-operative day 4) based on a programmed stimulation protocol delivered by Medtronic Pacing system analyser 2090 via a Medtronic pacemaker connected serially to the atrial epicardial pacing wires.
Atrial tissue biomarkers
Time frame: Right atrial appendage harvested at the time of venous cannulation and after separation from cardio-pulmonary bypass
Evaluation of production of reactive oxygen species
6 secondary outcomes
Post-operative recovery of left ventricular systolic and diastolic function
Time frame: Assessed by transthoracic echocardiography before surgery as well as before the day of first hospital discharge with an average of 5 days after surgery
Atrial tissue biomarkers
Time frame: Right atrial appendage harvested at the time of venous cannulation and after separation from cardio-pulmonary bypass
Adipose tissue biomarkers
Time frame: Epicardial,perivascular, mesothoracic and subcutaneous adipose tissue samples collected at the time of surgery
Vascular tissue biomarkers
Time frame: Surplus vessels from saphenous venous and internal mammary artery grafts collected at the time of surgery
Biomarkers in peripheral blood
Time frame: Peripheral blood samples processed to separate plasma/serum before surgery, on post operative day 3 and 5
Post operative atrial fibrillation detected by continuous ECG monitoring.
Time frame: Monitoring will commence soon after surgery and will be continued until the end of post operative day 5
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 7 Aug 2014.
- Background: PubMed 22192670Antoniades C, Demosthenous M, Reilly S, Margaritis M, Zhang MH, Antonopoulos A, Marinou K, Nahar K, Jayaram R, Tousoulis D, Bakogiannis C, Sayeed R, Triantafyllou C, Koumallos N, Psarros C, Miliou A, Stefanadis C, Channon KM, Casadei B. Myocardial redox state predicts in-hospital clinical outcome after cardiac surgery effects of short-term pre-operative statin treatment. J Am Coll Cardiol. 2012 Jan 3;59(1):60-70. doi: 10.1016/j.jacc.2011.08.062.
- Background: PubMed 21730307Antoniades C, Bakogiannis C, Leeson P, Guzik TJ, Zhang MH, Tousoulis D, Antonopoulos AS, Demosthenous M, Marinou K, Hale A, Paschalis A, Psarros C, Triantafyllou C, Bendall J, Casadei B, Stefanadis C, Channon KM. Rapid, direct effects of statin treatment on arterial redox state and nitric oxide bioavailability in human atherosclerosis via tetrahydrobiopterin-mediated endothelial nitric oxide synthase coupling. Circulation. 2011 Jul 19;124(3):335-45. doi: 10.1161/CIRCULATIONAHA.110.985150. Epub 2011 Jul 5.
- Background: PubMed 21844076Reilly SN, Jayaram R, Nahar K, Antoniades C, Verheule S, Channon KM, Alp NJ, Schotten U, Casadei B. Atrial sources of reactive oxygen species vary with the duration and substrate of atrial fibrillation: implications for the antiarrhythmic effect of statins. Circulation. 2011 Sep 6;124(10):1107-17. doi: 10.1161/CIRCULATIONAHA.111.029223. Epub 2011 Aug 15.
- Background: PubMed 20381820Chen WT, Krishnan GM, Sood N, Kluger J, Coleman CI. Effect of statins on atrial fibrillation after cardiac surgery: a duration- and dose-response meta-analysis. J Thorac Cardiovasc Surg. 2010 Aug;140(2):364-72. doi: 10.1016/j.jtcvs.2010.02.042. Epub 2010 Apr 9.
- Background: PubMed 20802247European Heart Rhythm Association; European Association for Cardio-Thoracic Surgery; Camm AJ, Kirchhof P, Lip GY, Schotten U, Savelieva I, Ernst S, Van Gelder IC, Al-Attar N, Hindricks G, Prendergast B, Heidbuchel H, Alfieri O, Angelini A, Atar D, Colonna P, De Caterina R, De Sutter J, Goette A, Gorenek B, Heldal M, Hohloser SH, Kolh P, Le Heuzey JY, Ponikowski P, Rutten FH. Guidelines for the management of atrial fibrillation: the Task Force for the Management of Atrial Fibrillation of the European Society of Cardiology (ESC). Eur Heart J. 2010 Oct;31(19):2369-429. doi: 10.1093/eurheartj/ehq278. Epub 2010 Aug 29. No abstract available.
- Background: PubMed 18174039Kim YM, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. Association of atrial nicotinamide adenine dinucleotide phosphate oxidase activity with the development of atrial fibrillation after cardiac surgery. J Am Coll Cardiol. 2008 Jan 1;51(1):68-74. doi: 10.1016/j.jacc.2007.07.085.
- Background: PubMed 16123335Kim YM, Guzik TJ, Zhang YH, Zhang MH, Kattach H, Ratnatunga C, Pillai R, Channon KM, Casadei B. A myocardial Nox2 containing NAD(P)H oxidase contributes to oxidative stress in human atrial fibrillation. Circ Res. 2005 Sep 30;97(7):629-36. doi: 10.1161/01.RES.0000183735.09871.61. Epub 2005 Aug 25.
- Background: PubMed 12963641Maack C, Kartes T, Kilter H, Schafers HJ, Nickenig G, Bohm M, Laufs U. Oxygen free radical release in human failing myocardium is associated with increased activity of rac1-GTPase and represents a target for statin treatment. Circulation. 2003 Sep 30;108(13):1567-74. doi: 10.1161/01.CIR.0000091084.46500.BB. Epub 2003 Sep 8.
- Background: PubMed 11922901Laufs U, Kilter H, Konkol C, Wassmann S, Bohm M, Nickenig G. Impact of HMG CoA reductase inhibition on small GTPases in the heart. Cardiovasc Res. 2002 Mar;53(4):911-20. doi: 10.1016/s0008-6363(01)00540-5.
- Background: PubMed 20837928Antoniades C, Bakogiannis C, Tousoulis D, Reilly S, Zhang MH, Paschalis A, Antonopoulos AS, Demosthenous M, Miliou A, Psarros C, Marinou K, Sfyras N, Economopoulos G, Casadei B, Channon KM, Stefanadis C. Preoperative atorvastatin treatment in CABG patients rapidly improves vein graft redox state by inhibition of Rac1 and NADPH-oxidase activity. Circulation. 2010 Sep 14;122(11 Suppl):S66-73. doi: 10.1161/CIRCULATIONAHA.109.927376.
- Background: PubMed 20969959Wojcicka G, Jamroz-Wisniewska A, Atanasova P, Chaldakov GN, Chylinska-Kula B, Beltowski J. Differential effects of statins on endogenous H2S formation in perivascular adipose tissue. Pharmacol Res. 2011 Jan;63(1):68-76. doi: 10.1016/j.phrs.2010.10.011. Epub 2010 Oct 20.
- Derived from this study: PubMed 33098411Jayaram R, Jones M, Reilly S, Crabtree MJ, Pal N, Goodfellow N, Nahar K, Simon J, Carnicer R, DeSilva R, Ratnatunga C, Petrou M, Sayeed R, Roalfe A, Channon KM, Bashir Y, Betts T, Hill M, Casadei B. Atrial nitroso-redox balance and refractoriness following on-pump cardiac surgery: a randomized trial of atorvastatin. Cardiovasc Res. 2022 Jan 7;118(1):184-195. doi: 10.1093/cvr/cvaa302.
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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.
Prof.Barbara Casadei, MD.DPhil.FRCP principal investigator
Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford
Dr.Raja Jayaram, MD principal investigator
Department of Cardiovascular Medicine, John Radcliffe Hospital, University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Atorvastatin in people with Disorder; Heart, Functional, Postoperative, Cardiac Surgery and Cardiac Insufficiency Following Cardiac Surgery, run by University of Oxford at 1 site in United Kingdom.
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 5 inclusion and 10 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 7 Aug 2014. 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 Kingdom. 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.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Post operative changes in the atrial effective refractory period (time frame: Serial measurements over the first 4 post operative days). 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 NCT01780740, which also lists 12 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 7 Aug 2014.