E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Trial 2: Condition under investigation: Postoperative atrial fibrillation after surgical aortic valve replacement. In patients no prior usage of statins: 14 days prior surgery to 30days after - Atorvastatin (Lipistad) 80mg vs placebo
Trial 3: Condition under investigation: Postoperative atrial fibrillation after surgical aortic valve replacement. In patients with prior usage of statins Discontinuation of statin vs continuation up to 14 days prior surgery to 30days after |
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E.1.1.1 | Medical condition in easily understood language |
The effects of statins on the development of postoperative atrial fibrillation in patients undergoing aortic valve replacement with surgical procedure. |
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E.1.1.2 | Therapeutic area | Diseases [C] - Cardiovascular Diseases [C14] |
MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | LLT |
E.1.2 | Classification code | 10003660 |
E.1.2 | Term | Atrial fibrillation and flutter |
E.1.2 | System Organ Class | 100000004849 |
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E.1.3 | Condition being studied is a rare disease | No |
E.2 Objective of the trial |
E.2.1 | Main objective of the trial |
Trial 2: The primary objective of this study is to establish if prophylactic regime administration of Atorvastatin 80 mg daily dose P.O. (started at least 7 to 14 days before surgery and continued until the 30th post-operative day included) in patients undergoing elective solitary SAVR with bioprosthesis and are statin-naïve leads to a reduction in the incidence of POAF evaluated by Holter monitoring.
Trial 3: The primary objective of study 3 is to investigate if discontinuance of statins in patients undergoing elective solitary SAVR with bioprosthesis with prior usage of statin the last 3 months and of at least 7 days is associated with risk of POAF or other complications including infections evaluated by Holter monitoring, clinical presentation and biochemical parameters. |
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E.2.2 | Secondary objectives of the trial |
Trial 2: The secondary objectives are to evaluate if prophylactic regime administration of Atorvastatin affects: • Early (≤30 days) and intermediate (1 year) clinical outcomes as outlined under secondary endpoints. • Prior to discharge echocardiographic outcomes as outlined under section 6.3. • Length of hospital care or the need of readmission.
Trial 3: The secondary objectives are to evaluate if discontinuance of statin is associated with: • Early (≤30 days) and intermediate (1 year) clinical outcomes as outlined under secondary endpoints. • Prior to discharge echocardiographic outcomes as outlined under secondary endpoints. • Length of hospital care or the need of readmission
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Trial 2 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 statin 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
Trial 3 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 statin in the past 3 months and of at least 7 days Age >60 years Willingness and provision of informed consent to be randomized
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E.4 | Principal exclusion criteria |
Trial 2: Prior history of atrial fibrillation Prior history of cardiac surgery Known adverse reaction to statin 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
Trial 3 Prior history of atrial fibrillation Prior history of cardiac surgery Hepatic dysfunction (Alanin-aminotransferase more than twice the upper limit) Creatinine >200 µmol/L |
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E.5 End points |
E.5.1 | Primary end point(s) |
Trial 2: Primary Outcome Measure: 1.Number of Participants with POAF - In-hospital In-hospital POAF assessed by Holter monitoring.
2.Number of Participants with POAF - Early Early assessed by anamnesis and electronic health record (EHR).
3.Number of Participants with POAF - Intermediate Intermediate POAF assessed by anamnesis and EHR.
Trial 3: Primary Outcome Measure: 1.Number of Participants with POAF - In-hospital In-hospital POAF assessed by Holter monitoring.
2.Number of Participants with POAF - Early Early assessed by anamnesis and electronic health record (EHR).
3.Number of Participants with POAF - Intermediate Intermediate POAF assessed by anamnesis and EHR.
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E.5.1.1 | Timepoint(s) of evaluation of this end point |
Trial2: 1 [Time Frame: In-hospital up to 10 days] 2 [Time Frame: Early (≤30 days) incidence of POAF] 3 [Time Frame: Intermediate (1 year) incidence of POAF]
Trial 3: 1 [Time Frame: In-hospital up to 10 days.] 2 [Time Frame: Early (≤30 days) incidence of POAF] 3 [Time Frame: Intermediate (1 year) incidence of POAF] |
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E.5.2 | Secondary end point(s) |
4) 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. 5) 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. 6) 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. 7) Myocardial injury - Tn Injury assessed by serial Troponin measurements. Unit:ng/l 8) Myocardial injury - CKMB Injury assessed by serial CKMB measurements. Unit: μg/l. 9) Stroke - Early Number of patients with stroke in each group. 10) Stroke - Intermediate Number of patients with stroke in each group. 11) Trans ischemic attack - Early Number of patients with trans ischemic attack in each group. 12) Trans ischemic attack - Intermediate Number of patients with trans ischemic attack in each group. 13) Myocardial infarction - Early Number of patients with Myocardial infarction in each group. 14) Myocardial infarction - Intermediate Number of patients with Myocardial infarction in each group. 15) Permanent pacemaker - Early Number of patients with Permanent pacemaker in each group. 16) Permanent pacemaker – Intermediate Number of patients with Permanent pacemaker in each group. 17) ICD implantation - Early Number of patients with ICD implantation in each group. 18) ICD implantation - Intermediate Number of patients with ICD implantation in each group. 19) Acute kidney injury - Early Number of patients with Acute kidney injury in each group. 20) Acute kidney injury - Intermediate Number of patients with Acute kidney injury in each group. 21) LVEF Describe echocardiography assessed differences in pre and postoperative measurements of LVEF(left ventricular ejection fraction) between groups. Unit: % 22) Strain Describe echocardiography assessed differences in pre and postoperative measurements of Strain between groups.Unit: %
23) Peak gradient Describe echocardiography assessed differences in pre and postoperative measurements of peak gradient between groups. Unit: mmHg 24) Mean gradient Describe echocardiography assessed differences in pre and postoperative measurements of mean gradient between groups. Unit: mmHg 25) TAPSE Describe echocardiography assessed differences in pre and postoperative measurements of TAPSE (tricuspid annular plane systolic excursion) between groups. Unit: mm 26) Length of stay on ICU Length of stay on ICU after surgery. Unit: Days 27) Length of stay in hospital Length of stay in hospital after surgery. Unit: Days
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E.5.2.1 | Timepoint(s) of evaluation of this end point |
Trial 2 and 3 4. In hospital up to 10 days 5. ≤30 days 6. 1 year 7. After surgery until discharge up to 10 days 8. After surgery until discharge up to 10 days 9. ≤30 days 10. 1 year 11. ≤30 days 12. 1 year 13. ≤30 days 14. 1 year 15. ≤30 days 16. 1 year 17. ≤30 days 18. 1 year 19. ≤30 days 20. 1 year 21. Before surgery compared to prior to discharge (3rd to 5th postoperative day) 22. Before surgery comp. to prior to discharge (3rd to 5th postop. day) 23. Before surgery comp. to prior to discharge (3rd to 5th postop. day) 24. Before surgery comp. to prior to discharge (3rd to 5th postop. day) 25. Before surgery comp. to prior to discharge (3rd to 5th postop. day) 26. Day of surgery to the day of discharge from ICU 27. Day of surgery to the day of discharge
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | No |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | No |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | No |
E.6.6 | Pharmacokinetic | No |
E.6.7 | Pharmacodynamic | No |
E.6.8 | Bioequivalence | No |
E.6.9 | Dose response | No |
E.6.10 | Pharmacogenetic | No |
E.6.11 | Pharmacogenomic | No |
E.6.12 | Pharmacoeconomic | No |
E.6.13 | Others | No |
E.7 | Trial type and phase |
E.7.1 | Human pharmacology (Phase I) | No |
E.7.1.1 | First administration to humans | No |
E.7.1.2 | Bioequivalence study | No |
E.7.1.3 | Other | No |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | No |
E.7.3 | Therapeutic confirmatory (Phase III) | No |
E.7.4 | Therapeutic use (Phase IV) | Yes |
E.8 Design of the trial |
E.8.1 | Controlled | Yes |
E.8.1.1 | Randomised | Yes |
E.8.1.2 | Open | No |
E.8.1.3 | Single blind | No |
E.8.1.4 | Double blind | No |
E.8.1.5 | Parallel group | No |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | Yes |
E.8.1.7.1 | Other trial design description |
Trial 2: Double blind, Trial 3: Open |
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E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
Trial 2: Placebo, Trial 3: discontinuation of medicin |
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E.8.2.4 | Number of treatment arms in the trial | 2 |
E.8.3 |
The trial involves single site in the Member State concerned
| Yes |
E.8.4 | The trial involves multiple sites in the Member State concerned | No |
E.8.5 | The trial involves multiple Member States | No |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | No |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.7 | Trial has a data monitoring committee | No |
E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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Trial 2: After 1 year of follow up from last enrolled subject. Total subjects: 266 Trial 3: After 1 year of follow up from last enrolled subject. Total subjects: 100 |
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E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | |
E.8.9.1 | In the Member State concerned months | |
E.8.9.1 | In the Member State concerned days | |