Postoperative Atrial FibrillationSTARCNCT05076019
Statin Therapy With Atorvastatin in Surgical Aortic Valve Replacement
A study testing Atorvastatin 80mg in people with Postoperative Atrial Fibrillation, run by Odense University Hospital at 1 site in Denmark.
Trial summary
Statins have rapid and significant actions that have potentially important (but not yet proven) implications for postoperative atrial fibrillation and cardiac protection in patients undergoing cardiac surgery. Read more about this study
- Who is it for?
- Ages 60 to 95 years
- Conditions the study is for
- Postoperative Atrial Fibrillation
- What is being tested?
- Atorvastatin 80mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 266 participants
- Where
- 1 siteDenmark
- Study dates
- 1 Feb 2022to 1 Dec 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 60 to 95 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing elective solitary SAVR with bioprosthesis
- Patients who are in sinus rhythm and not taking any anti-arrhythmic medication, other than beta-adrenergic blocking agents, at the time of surgery
- No prior use of HMG-CoA reductase inhibitors the last 3 months and at least 7 days prior to the time of surgery
- Age >60 years
- Willingness and provision of informed consent to be randomized
Who cannot join
- Prior history of atrial fibrillation
- Prior history of cardiac surgery
- Known adverse reaction to HMG-CoA reductase inhibitors
- Hepatic dysfunction (Alanin-aminotransferase more than twice the upper limit)
- Creatinine >200 µmol/L
- Known intolerance to statins or history of muscle toxicity with statins
- Known intolerance to any of the excipients in Lipistad
- Treatment with anti-viral medicine (glecaprevir/pibrentasvir) for hepatitis
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Denmark1 site, 1 recruiting
- Recruiting
Odense University Hospital
Odense, 5000
Lytfi Krasniqi, MD, 42772085 ext. 0045, Lytfi.Krasniqi@rsyd.dk
About this study
Official title: Statin Therapy With Atorvastatin in Surgical Aortic Valve Replacement - a Randomized Controlled Trial
Statins have rapid and significant actions that have potentially important (but not yet proven) implications for postoperative atrial fibrillation and cardiac protection in patients undergoing cardiac surgery.
The focus of this study is, therefore, on patients having surgical aortic valve replacement (with aortotomy) and the development of postoperative atrial fibrillation (POAF). Our aims are: to examine the ability of a clinically durable Atorvastatin prophylactic regime to prevent the development of POAF and other postoperative complications in these patients.
Read more
Patients will be randomized to Atorvastatin 80mg or placebo 7 to 14 days preoperative until 30 days postoperative - a total of 37 to 44 days of treatment.
The medication will be double blinded.
The randomized studie will address the following hypotheses in patients undergoing open heart operation with solitary aortic valve replacement with a bioprosthetic valve that
- 7 to 14 days preoperative and until 30 days postoperative treatment with Atorvastatin 80 mg daily reduces the incidence of POAF in statin-naïve patients.
Read the detailed description
Trial Participants:
Enrolment for the study is planned to start February 2022 and continue until 266 patients have been enrolled.
DEFINITION OF POAF:
Postoperative AF (I48) is defined as irregular RR-intervals without a traceable p-wave before each QRS complex during at least 30 seconds or entire 12-lead ECG in symptomatic or asymptomatic patients with no prior history of atrial fibrillation or flutter are considered4. Continuous ECG monitoring (8-lead ward monitor) will recognise AF during the entire hospitalization. Anamnesis, electronic health record (EHR), or confirmatory rhythm strip or 12-lead ECG of AF until 30th postoperative day are also considered.
We will also report the burden of atrial fibrillation, and treatment with a rate controlling drug, antiarrhythmic drug, or electrical cardioversion.
Course of action:
Patients undergoing elective surgical aortic valve replacement with bioprosthesis at the Department of Cardiac Surgery at Odense University Hospital will be offered participation in the study.
Potentially eligible patients will be screened according to inclusion/exclusion criteria at the time after eligibility of surgery. This is assessed at a multidisciplinary team (MDT) conference (with attendance of cardiologist, cardiac surgeons and anaesthesiologist) based on clinical evaluation, echocardiographic ultrasound, coronary angiography and lung function test.
Patients eligible to participate in the study will be presented with the information of the study at the time of their out-patient appointment, according to normal routine at Odense University Hospital. At this appointment the patient receives a physical examination and journal record is obtained by a cardiac surgeon (approximately 7 to 14 days prior to planned surgery).
The study-information will be given by one of the participating doctors, while the patient has been informed of the possibility of bringing an assessor of their choice. The information will be delivered in a quiet room blocked to other appointments in the Department of Cardiothoracic Surgery.
During this meeting the patient will be informed of the purpose of this study and the written patient information will be submitted in detail. Patients will be given as much time as wanted after the oral information has been delivered to decide if they wish to participate in the study. Patients will be offered the possibility to call one of the doctors taking part in this study during this time, in case of additional questions. Subjects can leave the study at any time for any reason if they wish to do so, without any consequences.
Signed informed consent will be provided prior to any research procedures. A subject is registered when signed informed consent has been provided and assigned a subject identification code by the computer-generated code. A subject is randomized when a treatment and a randomisation number has been provided. A subject is considered enrolled in the study once the subject is randomized.
Patient data from EHR will be conducted according to study endpoints after signed informed consent is provided. Signed consent gives sponsor and sponsors representatives
Randomization:
Allocation to a numbered treatment pack (Atorvastatin or placebo - blinded) Randomization scheme will be set-up by OPEN data manager with control for beta-blockers and age, and then randomization per se will be executed with the use of REDCap.
The following will be recorded at the day of randomization:
- Conduct information for baseline characteristics
- Transthoracic Echocardiography measurements
Collect baseline blood sample:
- Troponin, CK-MB, Creatinine, CRP
Commence study medication/treatment
Perioperative interventions and outcomes from the day of surgery to the day of discharge:
- Duration of aortic cross clamp (ACC), extracorporeal circulation (ECC), ventilatory support, intensive care unit stay period, hospital stay period
- Continue study medication
- Blood samples:
- Preoperative: Troponin, CK-MB, Creatinine, CRP, Plasma-Atorvastatin
- Serial troponin and CK-MB levels: (6, 24, 48, and 96 hours after surgery).
- Creatinine levels: 48 and 96 hours after surgery.
- CRP levels: 48 and 96 hours after surgery
- Monitor ECG by continuous Holter monitoring to commence as soon as possible after surgery and continue up to post-operative day 5 evening
- Transthoracic Echocardiography on post-operative day 3-5
- Record fluid intake and output during the first 48 hours following surgery based on IV fluids administration, blood transfusion (if applicable), oral/nasogastric intake, and urine plus surgical drain output
- Record intraoperative defibrillation, removal of external pacemaker, new PPM/ICD, vasopressors, blood transfusion, surgical re-exploration, renal replacement therapy, beta-blockers, ACEi/ARB, Amiodarone, Digoxin, Diuretics, Calcium channel blockers, Potassium supplements, NSAIDs or steroids, non-study statin, use of nephrotoxic antibiotics, contrast agents or potassium sparing diuretics (Yes/No)
Assessment at/after discharge from hospital:
- Continue study medications for 30 days after the surgery
- Phone call on the 30th postoperative day to evaluate symptoms of discomfort compatible with atrial fibrillation
- At the end of the study, all excess study medication can be returned at the local drugstore for safe disposal
- Patient data from EHR will be conducted according to study endpoints.
- Conditions
- Postoperative Atrial Fibrillation
- Being tested
- Atorvastatin 80mg, Placebo
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin 80mgDrug
Dosage: 80 mg Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative
PlaceboDrug
Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative
| Study group | Role | What they receive |
|---|---|---|
| Atorvastatin 80 mg | Experimental | Dosage: 80 mg Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative Receives: Drug: Atorvastatin 80mg |
| Placebo | Placebo comparator | Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants with POAF - In-hospital
In-hospital incidence of POAF assessed by continuous ECG monitoring (8-lead ward monitor).
Measured: In-hospital up to 10 days
Number of Participants with POAF - Early
Early assessed by anamnesis, electronic health record (EHR), or confirmatory rhythm strip or 12-lead ECG of AF
Measured: Early (≤30 days) incidence of POAF
Total duration of POAF - In-hospital
Total duration of POAF episodes experienced in-hospital (unit: hours)
Measured: In-hospital up to 10 days
Secondary outcomes (24)
Rate of All-cause mortality - In-hospital
To evaluate the effect of prophylactic regime administration of Atorvastatin on clinical outcomes.
Number of deaths in each group.
Measured: In hospital up to 10 days
Rate of All-cause mortality - Early
To evaluate the effect of prophylactic regime administration of Atorvastatin on clinical outcomes.
Number of deaths in each group.
Measured: Early (≤30 days)
Rate of All-cause mortality - intermediate
To evaluate the effect of prophylactic regime administration of Atorvastatin on clinical outcomes.
Number of deaths in each group.
Measured: intermediate (1 year)
Myocardial injury - Tn
Injury assessed by serial Troponin measurements. Unit:ng/l
Measured: After surgery until discharge up to 10 days.
Myocardial injury - CKMB
Injury assessed by serial CKMB measurements. Unit: μg/l.
Measured: After surgery until discharge up to 10 days.
Stroke - Early
Number of patients with stroke in each group.
Measured: Early (≤30 days)
Stroke - Intermediate
Number of patients with stroke in each group.
Measured: Intermediate (1 year)
Trans ischemic attack - Early
Number of patients with trans ischemic attack in each group.
Measured: Early (≤30 days)
Trans ischemic attack - Intermediate
Number of patients with trans ischemic attack in each group.
Measured: Intermediate (1 year)
Myocardial infarction - Early
Number of patients with Myocardial infarction in each group.
Measured: Early (≤30 days)
Myocardial infarction - Intermediate
Number of patients with Myocardial infarction in each group.
Measured: Intermediate (1 year)
Permanent pacemaker - Early
Number of patients with Permanent pacemaker in each group.
Measured: Early (≤30 days)
Permanent pacemaker - Intermediate
Number of patients with Permanent pacemaker in each group.
Measured: Intermediate (1 year)
ICD implantation - Early
Number of patients with ICD implantation in each group.
Measured: Early (≤30 days)
ICD implantation - Intermediate
Number of patients with ICD implantation in each group.
Measured: Intermediate (1 year)
Acute kidney injury - Early
Number of patients with Acute kidney injury in each group.
Measured: Early (≤30 days)
Acute kidney injury - Intermediate
Number of patients with Acute kidney injury in each group.
Measured: Intermediate (1 year)
LVEF
Describe echocardiography assessed differences in pre and postoperative measurements of LVEF(left ventricular ejection fraction) between groups. Unit: %
Measured: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Strain
Describe echocardiography assessed differences in pre and postoperative measurements of Strain between groups.Unit: %
Measured: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Peak gradient
Describe echocardiography assessed differences in pre and postoperative measurements of peak gradient between groups. Unit: mmHg
Measured: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Mean gradient
Describe echocardiography assessed differences in pre and postoperative measurements of mean gradient between groups. Unit: mmHg
Measured: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
TAPSE
Describe echocardiography assessed differences in pre and postoperative measurements of TAPSE (tricuspid annular plane systolic excursion) between groups. Unit: mm
Measured: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Length of stay on ICU
Length of stay on ICU after surgery. Unit: Days
Measured: Day of surgery to the day of discharge from ICU. Up to 52 weeks.
Length of stay in hospital
Length of stay in hospital after surgery. Unit: Days
Measured: Day of surgery to the day of discharge. Up to 52 weeks.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Oct 2021
- Study start1 Feb 2022
- Primary completion1 Dec 2027 (estimated)
- Study completion1 Dec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (48)Papers the sponsor has linked to this study.
- Other trials for Postoperative Atrial FibrillationStudies of the same condition, open and under way.
- More trials run by Odense University HospitalThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Intervention: Atorvastatin, n = 133 Dose: 80 mg/daily P.O. Length of preoperative statin exposure: 7 to 14 days prior to surgery Length of postoperative exposure: 30 days Control group: Placebo, n = 133 Study parameters Incidence, placebo group: 36% Incidence, Atorvastatin group: 20% Alpha: 0.05 Beta: 0.2 Power: 0.8 Enrolment ratio: 1:1 Sample size Placebo: 133 Atorvastatin: 133
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 266 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Odense University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Odense Patient Data Explorative Network, GCP-unit at Odense University Hospital
- Responsible party
- Principal investigator, Lars Peter Riber, Odense University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05076019
- Sponsor's protocol ID
- STARC210421_2
- Acronym
- STARC
- Status last verified
- Oct 2024
- First submitted
- 19 Aug 2021
- Last updated
- 8 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be available in anonymized form in accordance with GDPR upon reasonable request. Rules for external researchers to apply for and access data will be laid out towards the end of the study.
Publications
LaPar DJ, Crosby IK, Rich JB, Fonner E Jr, Kron IL, Ailawadi G, Speir AM; Investigators for Virginia Cardiac Surgery Quality Initiative. A contemporary cost analysis of postoperative morbidity after coronary artery bypass grafting with and without concomitant aortic valve replacement to improve patient quality and cost-effective care. Ann Thorac Surg. 2013 Nov;96(5):1621-7. doi: 10.1016/j.athoracsur.2013.05.050. Epub 2013 Aug 21.
PubMed 23972932Brown JM, O'Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg. 2009 Jan;137(1):82-90. doi: 10.1016/j.jtcvs.2008.08.015.
PubMed 19154908Maesen B, Nijs J, Maessen J, Allessie M, Schotten U. Post-operative atrial fibrillation: a maze of mechanisms. Europace. 2012 Feb;14(2):159-74. doi: 10.1093/europace/eur208. Epub 2011 Aug 6.
PubMed 21821851Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Feb 1;42(5):373-498. doi: 10.1093/eurheartj/ehaa612. No abstract available.
PubMed 32860505Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, Whitlock RP. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003611. doi: 10.1002/14651858.CD003611.pub3.
PubMed 23440790AlTurki A, Marafi M, Proietti R, Cardinale D, Blackwell R, Dorian P, Bessissow A, Vieira L, Greiss I, Essebag V, Healey JS, Huynh T. Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery: A Systematic Review and Meta-Analysis. Circ Arrhythm Electrophysiol. 2020 Jan;13(1):e007437. doi: 10.1161/CIRCEP.119.007437. Epub 2020 Jan 16.
PubMed 31944855Dobrev D, Aguilar M, Heijman J, Guichard JB, Nattel S. Postoperative atrial fibrillation: mechanisms, manifestations and management. Nat Rev Cardiol. 2019 Jul;16(7):417-436. doi: 10.1038/s41569-019-0166-5.
PubMed 30792496Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg. 2017 Oct 1;52(4):665-672. doi: 10.1093/ejcts/ezx039.
PubMed 28369234Aguilar M, Dobrev D, Nattel S. Postoperative Atrial Fibrillation: Features, Mechanisms, and Clinical Management. Card Electrophysiol Clin. 2021 Mar;13(1):123-132. doi: 10.1016/j.ccep.2020.11.010.
PubMed 33516390Kim 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 18174039Antoniades 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 22192670Scott L Jr, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019 Jul 15;287:195-200. doi: 10.1016/j.ijcard.2018.10.020. Epub 2018 Oct 4.
PubMed 30316645Wong CX, Ganesan AN, Selvanayagam JB. Epicardial fat and atrial fibrillation: current evidence, potential mechanisms, clinical implications, and future directions. Eur Heart J. 2017 May 1;38(17):1294-1302. doi: 10.1093/eurheartj/ehw045.
PubMed 26935271Halonen J, Halonen P, Jarvinen O, Taskinen P, Auvinen T, Tarkka M, Hippelainen M, Juvonen T, Hartikainen J, Hakala T. Corticosteroids for the prevention of atrial fibrillation after cardiac surgery: a randomized controlled trial. JAMA. 2007 Apr 11;297(14):1562-7. doi: 10.1001/jama.297.14.1562.
PubMed 17426275Zheng Z, Jayaram R, Jiang L, Emberson J, Zhao Y, Li Q, Du J, Guarguagli S, Hill M, Chen Z, Collins R, Casadei B. Perioperative Rosuvastatin in Cardiac Surgery. N Engl J Med. 2016 May 5;374(18):1744-53. doi: 10.1056/NEJMoa1507750.
PubMed 27144849
Study at a glance
From the registry record, last updated by the sponsor on 8 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Statin Therapy With Atorvastatin in Surgical Aortic Valve Replacement - a Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05076019
- Acronym / sponsor ID
- STARC / STARC210421_2
- Conditions
- Postoperative Atrial Fibrillation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 266 participants (estimated)
- Lead sponsor
- Odense University HospitalUniversity, hospital or other
- Collaborators
- Odense Patient Data Explorative Network, GCP-unit at Odense University Hospital
- Study start
- 1 Feb 2022 (actual)
- Primary completion
- 1 Dec 2027 (estimated)
- Study completion
- 1 Dec 2027 (estimated)
- First posted
- 13 Oct 2021 (actual)
- 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.
Statins have rapid and significant actions that have potentially important (but not yet proven) implications for postoperative atrial fibrillation and cardiac protection in patients undergoing cardiac surgery.
The focus of this study is, therefore, on patients having surgical aortic valve replacement (with aortotomy) and the development of postoperative atrial fibrillation (POAF). Our aims are: to examine the ability of a clinically durable Atorvastatin prophylactic regime to prevent the development of POAF and other postoperative complications in these patients.
Patients will be randomized to Atorvastatin 80mg or placebo 7 to 14 days preoperative until 30 days postoperative - a total of 37 to 44 days of treatment.
The medication will be double blinded.
The randomized studie will address the following hypotheses in patients undergoing open heart operation with solitary aortic valve replacement with a bioprosthetic valve that
- 7 to 14 days preoperative and until 30 days postoperative treatment with Atorvastatin 80 mg daily reduces the incidence of POAF in statin-naïve patients.
Detailed description
Trial Participants:
Enrolment for the study is planned to start February 2022 and continue until 266 patients have been enrolled.
DEFINITION OF POAF:
Postoperative AF (I48) is defined as irregular RR-intervals without a traceable p-wave before each QRS complex during at least 30 seconds or entire 12-lead ECG in symptomatic or asymptomatic patients with no prior history of atrial fibrillation or flutter are considered4. Continuous ECG monitoring (8-lead ward monitor) will recognise AF during the entire hospitalization. Anamnesis, electronic health record (EHR), or confirmatory rhythm strip or 12-lead ECG of AF until 30th postoperative day are also considered.
We will also report the burden of atrial fibrillation, and treatment with a rate controlling drug, antiarrhythmic drug, or electrical cardioversion.
Course of action:
Patients undergoing elective surgical aortic valve replacement with bioprosthesis at the Department of Cardiac Surgery at Odense University Hospital will be offered participation in the study.
Potentially eligible patients will be screened according to inclusion/exclusion criteria at the time after eligibility of surgery. This is assessed at a multidisciplinary team (MDT) conference (with attendance of cardiologist, cardiac surgeons and anaesthesiologist) based on clinical evaluation, echocardiographic ultrasound, coronary angiography and lung function test.
Patients eligible to participate in the study will be presented with the information of the study at the time of their out-patient appointment, according to normal routine at Odense University Hospital. At this appointment the patient receives a physical examination and journal record is obtained by a cardiac surgeon (approximately 7 to 14 days prior to planned surgery).
The study-information will be given by one of the participating doctors, while the patient has been informed of the possibility of bringing an assessor of their choice. The information will be delivered in a quiet room blocked to other appointments in the Department of Cardiothoracic Surgery.
During this meeting the patient will be informed of the purpose of this study and the written patient information will be submitted in detail. Patients will be given as much time as wanted after the oral information has been delivered to decide if they wish to participate in the study. Patients will be offered the possibility to call one of the doctors taking part in this study during this time, in case of additional questions. Subjects can leave the study at any time for any reason if they wish to do so, without any consequences.
Signed informed consent will be provided prior to any research procedures. A subject is registered when signed informed consent has been provided and assigned a subject identification code by the computer-generated code. A subject is randomized when a treatment and a randomisation number has been provided. A subject is considered enrolled in the study once the subject is randomized.
Patient data from EHR will be conducted according to study endpoints after signed informed consent is provided. Signed consent gives sponsor and sponsors representatives
Randomization:
Allocation to a numbered treatment pack (Atorvastatin or placebo - blinded) Randomization scheme will be set-up by OPEN data manager with control for beta-blockers and age, and then randomization per se will be executed with the use of REDCap.
The following will be recorded at the day of randomization:
- Conduct information for baseline characteristics
- Transthoracic Echocardiography measurements
Collect baseline blood sample:
- Troponin, CK-MB, Creatinine, CRP
Commence study medication/treatment
Perioperative interventions and outcomes from the day of surgery to the day of discharge:
- Duration of aortic cross clamp (ACC), extracorporeal circulation (ECC), ventilatory support, intensive care unit stay period, hospital stay period
- Continue study medication
- Blood samples:
- Preoperative: Troponin, CK-MB, Creatinine, CRP, Plasma-Atorvastatin
- Serial troponin and CK-MB levels: (6, 24, 48, and 96 hours after surgery).
- Creatinine levels: 48 and 96 hours after surgery.
- CRP levels: 48 and 96 hours after surgery
- Monitor ECG by continuous Holter monitoring to commence as soon as possible after surgery and continue up to post-operative day 5 evening
- Transthoracic Echocardiography on post-operative day 3-5
- Record fluid intake and output during the first 48 hours following surgery based on IV fluids administration, blood transfusion (if applicable), oral/nasogastric intake, and urine plus surgical drain output
- Record intraoperative defibrillation, removal of external pacemaker, new PPM/ICD, vasopressors, blood transfusion, surgical re-exploration, renal replacement therapy, beta-blockers, ACEi/ARB, Amiodarone, Digoxin, Diuretics, Calcium channel blockers, Potassium supplements, NSAIDs or steroids, non-study statin, use of nephrotoxic antibiotics, contrast agents or potassium sparing diuretics (Yes/No)
Assessment at/after discharge from hospital:
- Continue study medications for 30 days after the surgery
- Phone call on the 30th postoperative day to evaluate symptoms of discomfort compatible with atrial fibrillation
- At the end of the study, all excess study medication can be returned at the local drugstore for safe disposal
- Patient data from EHR will be conducted according to study endpoints.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Intervention: Atorvastatin, n = 133 Dose: 80 mg/daily P.O. Length of preoperative statin exposure: 7 to 14 days prior to surgery Length of postoperative exposure: 30 days Control group: Placebo, n = 133 Study parameters Incidence, placebo group: 36% Incidence, Atorvastatin group: 20% Alpha: 0.05 Beta: 0.2 Power: 0.8 Enrolment ratio: 1:1 Sample size Placebo: 133 Atorvastatin: 133
| Arm | Type | Receives |
|---|---|---|
| Atorvastatin 80 mg | Experimental | Drug: Atorvastatin 80mgDosage: 80 mg Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative |
| Placebo | Placebo comparator | Drug: PlaceboForm: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative |
Who may qualify
- Ages
- 60 to 95 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing elective solitary SAVR with bioprosthesis
- Patients who are in sinus rhythm and not taking any anti-arrhythmic medication, other than beta-adrenergic blocking agents, at the time of surgery
- No prior use of HMG-CoA reductase inhibitors the last 3 months and at least 7 days prior to the time of surgery
- Age >60 years
- Willingness and provision of informed consent to be randomized
Key exclusion criteria (8 listed)
- Prior history of atrial fibrillation
- Prior history of cardiac surgery
- Known adverse reaction to HMG-CoA reductase inhibitors
- Hepatic dysfunction (Alanin-aminotransferase more than twice the upper limit)
- Creatinine >200 µmol/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 |
|---|---|---|
| Atorvastatin 80mgDosage: 80 mg Form: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative | Drug | Atorvastatin 80 mg |
| PlaceboForm: Tablets Frequency: 1 tabl. per day. Duration: From 7 to 14 days prior to surgery until 30 days postoperative | Drug | Placebo |
Primary outcome
Number of Participants with POAF - In-hospital
Time frame: In-hospital up to 10 days
In-hospital incidence of POAF assessed by continuous ECG monitoring (8-lead ward monitor).
Number of Participants with POAF - Early
Time frame: Early (≤30 days) incidence of POAF
Early assessed by anamnesis, electronic health record (EHR), or confirmatory rhythm strip or 12-lead ECG of AF
Total duration of POAF - In-hospital
Time frame: In-hospital up to 10 days
Total duration of POAF episodes experienced in-hospital (unit: hours)
24 secondary outcomes
Rate of All-cause mortality - In-hospital
Time frame: In hospital up to 10 days
Rate of All-cause mortality - Early
Time frame: Early (≤30 days)
Rate of All-cause mortality - intermediate
Time frame: intermediate (1 year)
Myocardial injury - Tn
Time frame: After surgery until discharge up to 10 days.
Myocardial injury - CKMB
Time frame: After surgery until discharge up to 10 days.
Stroke - Early
Time frame: Early (≤30 days)
Stroke - Intermediate
Time frame: Intermediate (1 year)
Trans ischemic attack - Early
Time frame: Early (≤30 days)
Trans ischemic attack - Intermediate
Time frame: Intermediate (1 year)
Myocardial infarction - Early
Time frame: Early (≤30 days)
Myocardial infarction - Intermediate
Time frame: Intermediate (1 year)
Permanent pacemaker - Early
Time frame: Early (≤30 days)
Permanent pacemaker - Intermediate
Time frame: Intermediate (1 year)
ICD implantation - Early
Time frame: Early (≤30 days)
ICD implantation - Intermediate
Time frame: Intermediate (1 year)
Acute kidney injury - Early
Time frame: Early (≤30 days)
Acute kidney injury - Intermediate
Time frame: Intermediate (1 year)
LVEF
Time frame: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Strain
Time frame: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Peak gradient
Time frame: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Mean gradient
Time frame: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
TAPSE
Time frame: Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).
Length of stay on ICU
Time frame: Day of surgery to the day of discharge from ICU. Up to 52 weeks.
Length of stay in hospital
Time frame: Day of surgery to the day of discharge. Up to 52 weeks.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Oct 2024.
- Background: PubMed 23972932LaPar DJ, Crosby IK, Rich JB, Fonner E Jr, Kron IL, Ailawadi G, Speir AM; Investigators for Virginia Cardiac Surgery Quality Initiative. A contemporary cost analysis of postoperative morbidity after coronary artery bypass grafting with and without concomitant aortic valve replacement to improve patient quality and cost-effective care. Ann Thorac Surg. 2013 Nov;96(5):1621-7. doi: 10.1016/j.athoracsur.2013.05.050. Epub 2013 Aug 21.
- Background: PubMed 19154908Brown JM, O'Brien SM, Wu C, Sikora JA, Griffith BP, Gammie JS. Isolated aortic valve replacement in North America comprising 108,687 patients in 10 years: changes in risks, valve types, and outcomes in the Society of Thoracic Surgeons National Database. J Thorac Cardiovasc Surg. 2009 Jan;137(1):82-90. doi: 10.1016/j.jtcvs.2008.08.015.
- Background: PubMed 21821851Maesen B, Nijs J, Maessen J, Allessie M, Schotten U. Post-operative atrial fibrillation: a maze of mechanisms. Europace. 2012 Feb;14(2):159-74. doi: 10.1093/europace/eur208. Epub 2011 Aug 6.
- Background: PubMed 32860505Hindricks G, Potpara T, Dagres N, Arbelo E, Bax JJ, Blomstrom-Lundqvist C, Boriani G, Castella M, Dan GA, Dilaveris PE, Fauchier L, Filippatos G, Kalman JM, La Meir M, Lane DA, Lebeau JP, Lettino M, Lip GYH, Pinto FJ, Thomas GN, Valgimigli M, Van Gelder IC, Van Putte BP, Watkins CL; ESC Scientific Document Group. 2020 ESC Guidelines for the diagnosis and management of atrial fibrillation developed in collaboration with the European Association for Cardio-Thoracic Surgery (EACTS): The Task Force for the diagnosis and management of atrial fibrillation of the European Society of Cardiology (ESC) Developed with the special contribution of the European Heart Rhythm Association (EHRA) of the ESC. Eur Heart J. 2021 Feb 1;42(5):373-498. doi: 10.1093/eurheartj/ehaa612. No abstract available.
- Background: PubMed 23440790Arsenault KA, Yusuf AM, Crystal E, Healey JS, Morillo CA, Nair GM, Whitlock RP. Interventions for preventing post-operative atrial fibrillation in patients undergoing heart surgery. Cochrane Database Syst Rev. 2013 Jan 31;2013(1):CD003611. doi: 10.1002/14651858.CD003611.pub3.
- Background: PubMed 31944855AlTurki A, Marafi M, Proietti R, Cardinale D, Blackwell R, Dorian P, Bessissow A, Vieira L, Greiss I, Essebag V, Healey JS, Huynh T. Major Adverse Cardiovascular Events Associated With Postoperative Atrial Fibrillation After Noncardiac Surgery: A Systematic Review and Meta-Analysis. Circ Arrhythm Electrophysiol. 2020 Jan;13(1):e007437. doi: 10.1161/CIRCEP.119.007437. Epub 2020 Jan 16.
- Background: PubMed 30792496Dobrev D, Aguilar M, Heijman J, Guichard JB, Nattel S. Postoperative atrial fibrillation: mechanisms, manifestations and management. Nat Rev Cardiol. 2019 Jul;16(7):417-436. doi: 10.1038/s41569-019-0166-5.
- Background: PubMed 28369234Greenberg JW, Lancaster TS, Schuessler RB, Melby SJ. Postoperative atrial fibrillation following cardiac surgery: a persistent complication. Eur J Cardiothorac Surg. 2017 Oct 1;52(4):665-672. doi: 10.1093/ejcts/ezx039.
- Background: PubMed 33516390Aguilar M, Dobrev D, Nattel S. Postoperative Atrial Fibrillation: Features, Mechanisms, and Clinical Management. Card Electrophysiol Clin. 2021 Mar;13(1):123-132. doi: 10.1016/j.ccep.2020.11.010.
- 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 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 30316645Scott L Jr, Li N, Dobrev D. Role of inflammatory signaling in atrial fibrillation. Int J Cardiol. 2019 Jul 15;287:195-200. doi: 10.1016/j.ijcard.2018.10.020. Epub 2018 Oct 4.
- Individual participant dataSharing planned: Yes. Data will be available in anonymized form in accordance with GDPR upon reasonable request. Rules for external researchers to apply for and access data will be laid out towards the end of the study.
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Atorvastatin 80mg in people with Postoperative Atrial Fibrillation, run by Odense University Hospital at 1 site in Denmark.
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 8 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: looking for participants now, as of the sponsor's last update on 8 Oct 2024. 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 Denmark. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Lytfi Krasniqi, MD (42772085, Lytfi.krasniqi@rsyd.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants with POAF - In-hospital (time frame: In-hospital up to 10 days). The study lists 3 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 NCT05076019, which also lists 48 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 8 Oct 2024.