Post-Operative Atrial Fibrillation After Surgical Aortic Valve Replacement and the Influence of Statins

Sponsor

Lars Peter Riber (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05062239

Collaborator

Odense Patient Data Explorative Network (Other), GCP-unit at Odense University Hospital (Other)

100

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief 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.

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 investigate the risk of POAF, infection or other complications after SAVR in continuous versus preoperative discontinuous treatment with statins.

The study is a single centre randomized controlled trial with continuance treatment with statin vs. discontinuance (7 to 14 days prior surgery until the 30th post-operative day included), on patients undergoing elective solitary SAVR with bioprosthesis with prior usage of statins the last 3 months and of at least 7 days.

This randomized studies will address 2 separate hypotheses in patients undergoing open heart operation with solitary aortic valve replacement with a bioprosthetic valve that

Discontinuation of HMG-CoA reductase inhibitors 7 to 14 days preoperative until 30 days postoperative of AVR in patients with prior use of HMG-CoA reductase inhibitors is not associated with increased early (<30 days) risk of POAF.
Discontinuation of HMG-CoA reductase inhibitors 7 to 14 days preoperative until 30 days postoperative of AVR in patients with prior use of HMG-CoA reductase inhibitors is not associated with increased early (<30 days) and intermediate (<1 year) risk of mortality, MI, stroke and rehospitalisation.

Condition or Disease	Intervention/Treatment	Phase
Postoperative Atrial Fibrillation	Drug: Discontinuance of treatment with statins 7 to 14 days prior to surgery until 30 days postoperative Drug: No-intervention.	N/A

Detailed Description

Trial Participants:

Enrolment for the study is planned to start February 2022 and continue until 100 patients have been enrolled.

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 (continuance or discontinuance of statin therapy) Randomization scheme will be set-up by OPEN data manager with control for beta-blockers and age (60-65, 66-70, 71-80, >80), 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 intervention

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 intervention
Blood samples:
Preoperative: Troponin, CK-MB, Creatinine, CRP, Plasma-Atorvastatin
Serial troponin and CK-MB levels: (6, 24, 48, and 120 hours after surgery).
Creatinine levels: 48 and 120 hours after surgery.
CRP levels: 48 and 120 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 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

Study Type:

Interventional

Anticipated Enrollment :

100 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

Discontinuous of statin Intervention: Discontinuous of statin, n = 50 Length of preoperative discontinuous: 7 to 14 days prior to surgery Length of postoperative discontinuous: 30 days Control group: continuing medication, n = 50 No withdrawal study could be found in the literature. We therefore estimate that 100 patients with 50 patients in each group will be enough to observe significant differences, if withdrawal statin should be a clinically manifested issue for the risk of POAF from 36% to 66%. Sample size Continuance of statins: 50 Discontinuance of statins: 50Discontinuous of statin Intervention: Discontinuous of statin, n = 50 Length of preoperative discontinuous: 7 to 14 days prior to surgery Length of postoperative discontinuous: 30 days Control group: continuing medication, n = 50 No withdrawal study could be found in the literature. We therefore estimate that 100 patients with 50 patients in each group will be enough to observe significant differences, if withdrawal statin should be a clinically manifested issue for the risk of POAF from 36% to 66%. Sample size Continuance of statins: 50 Discontinuance of statins: 50

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

Post-Operative Atrial Fibrillation After Surgical Aortic Valve Replacement and the Influence of Statins - Randomized Controlled Trial

Anticipated Study Start Date :

Feb 1, 2022

Anticipated Primary Completion Date :

Feb 1, 2027

Anticipated Study Completion Date :

Feb 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Continuance Continuance prior statin therapy.	Drug: No-intervention. Continuance of prior statin therapy
Experimental: Discontinuance Discontinuance prior statin therapy. Duration: From 7 to 14 days prior to surgery until 30 days postoperative	Drug: Discontinuance of treatment with statins 7 to 14 days prior to surgery until 30 days postoperative Discontinuance of prior statin therapy

Arm

Intervention/Treatment

Active Comparator: Continuance

Continuance prior statin therapy.

Drug: No-intervention.

Continuance of prior statin therapy

Experimental: Discontinuance

Discontinuance prior statin therapy. Duration: From 7 to 14 days prior to surgery until 30 days postoperative

Drug: Discontinuance of treatment with statins 7 to 14 days prior to surgery until 30 days postoperative

Discontinuance of prior statin therapy

Outcome Measures

Primary Outcome Measures

Number of Participants with POAF - In-hospital [In-hospital up to 10 days.]
In-hospital POAF assessed by Holter monitoring.
Number of Participants with POAF - Early [Early (≤30 days) incidence of POAF]
Early assessed by anamnesis and electronic health record (EHR).
Number of Participants with POAF - Intermediate [Intermediate (1 year) incidence of POAF]
Intermediate POAF assessed by anamnesis and EHR.

Secondary Outcome Measures

Rate of all-cause mortality - In-hospital [In-hospital up to 10 days.]
Number of deaths in each group.
Rate of all-cause mortality - Early [Early (≤30 days)]
Number of deaths in each group.
Rate of all-cause mortality - intermediate [Intermediate (1 year)]
Number of deaths in each group.
Myocardial injury - Tn [After surgery until discharge up to 10 days]
Injury assessed by serial Troponin measurements. Unit:ng/l
Myocardial injury - CKMB [After surgery until discharge up to 10 days]
Injury assessed by serial CKMB measurements. Unit: μg/l.
Stroke - Early [Early (≤30 days).]
Number of patients with stroke in each group.
Stroke - Intermediate [Intermediate (1 year)]
Number of patients with stroke in each group.
Trans ischemic attack - Early [Early (≤30 days)]
Number of patients with trans ischemic attack in each group.
Trans ischemic attack - Intermediate [Intermediate (1 year)]
Number of patients with trans ischemic attack in each group.
Myocardial infarction - Early [Early (≤30 days)]
Number of patients with Myocardial infarction in each group.
Myocardial infarction - Intermediate [Intermediate (1 year)]
Number of patients with Myocardial infarction in each group.
Permanent pacemaker - Early [Early (≤30 days)]
Number of patients with Permanent pacemaker in each group.
Permanent pacemaker - Intermediate [Intermediate (1 year)]
Number of patients with Permanent pacemaker in each group.
ICD implantation - Early [Early (≤30 days)]
Number of patients with ICD implantation in each group.
ICD implantation - Intermediate [Intermediate (1 year)]
Number of patients with ICD implantation in each group.
Acute kidney injury - Early [Early (≤30 days)]
Number of patients with Acute kidney injury in each group.
Acute kidney injury - Intermediate [Intermediate (1 year)]
Number of patients with Acute kidney injury in each group.
LVEF [Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).]
Describe echocardiography assessed differences in pre and postoperative measurements of LVEF(left ventricular ejection fraction) between groups. Unit: %
Strain [Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).]
Describe echocardiography assessed differences in pre and postoperative measurements of Strain between groups.Unit: %
Peak gradient [Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).]
Describe echocardiography assessed differences in pre and postoperative measurements of peak gradient between groups. Unit: mmHg
Mean gradient [Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).]
Describe echocardiography assessed differences in pre and postoperative measurements of mean gradient between groups. Unit: mmHg
TAPSE [Before surgery compared with prior to discharge (On the 3rd to 5th postoperative day).]
Describe echocardiography assessed differences in pre and postoperative measurements of TAPSE (tricuspid annular plane systolic excursion) between groups. Unit: mm
Length of stay on ICU [Day of surgery to the day of discharge from ICU. Up to 52 weeks.]
Length of stay on ICU after surgery. Unit: Days
Length of stay in hospital [Day of surgery to the day of discharge from the hospital. Up to 52 weeks.]
Length of stay in hospital after surgery. Unit: Days

Eligibility Criteria

Criteria

Ages Eligible for Study:

60 Years to 95 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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
In treatment with HMG-CoA reductase inhibitors in the past 3 months and of at least 7 days
Age >60 years
Willingness and provision of informed consent to be randomized

Exclusion Criteria:

Prior history of atrial fibrillation
Prior history of cardiac surgery
Hepatic dysfunction (Alanin-aminotransferase more than twice the upper limit)
Creatinine >200 µmol/L

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Lars Peter Riber
Odense Patient Data Explorative Network
GCP-unit at Odense University Hospital

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Lars Peter Riber, MD, Associate Professor, Ph.D., DMSc, Odense University Hospital

ClinicalTrials.gov Identifier:

NCT05062239

Other Study ID Numbers:

STARC210421_3
2021-002210-13

First Posted:

Sep 30, 2021

Last Update Posted:

Sep 30, 2021

Last Verified:

Sep 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Additional relevant MeSH terms:

Atrial Fibrillation

Study Results

No Results Posted as of Sep 30, 2021