E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
POST-OPERATIVE ATRIAL FIBRILLATION |
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MedDRA Classification |
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 13 |
E.1.2 | Level | SOC |
E.1.2 | Classification code | 10003658 |
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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 |
To establish whether perioperative administration (for 6 to 1 day before surgery and 5 days after) of atorvastatin (80 mg od) in patients undergoing elective cardiac surgery •Prevents shortening of the atrial effective refractory period (a marker of atrial electrical remodelling leading to AF)after surgery •Leads to a reduction in atrial production of reactive oxygen species (an independent predictor of post-operative AF)and systemic inflammatory markers.
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E.2.2 | Secondary objectives of the trial |
To evaluate the effect of perioperative administration of high-dose atorvastatin on the activity of atrial oxidase systems (the enzymes producing reactive oxygen species in the atrial tissue),inflammation in atrial tissue,on the postoperative AF burden (evaluated by ambulatory ECG monitoring)and contractile function of the heart.
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients who are: 1. Willing and able to give informed consent for participation in the study 2. In normal sinus rhythm at the time of surgery 3. Stable and requiring elective cardiac surgery. 4. Able (in the Investigators’ opinion) and willing to comply with all study requirements. 5. Willing to allow his or her General Practitioner and consultant, if appropriate, to be notified of participation in the study.
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E.4 | Principal exclusion criteria |
Age>80yrs 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 preoperative ALT >2-fold the upper limit of normal or alcohol abuse Creatinine >200 umol/L Untreated hypothyroidism 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. |
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E.5 End points |
E.5.1 | Primary end point(s) |
To establish whether perioperative administration (for 6 to 1 day before surgery and 5 days after) of atorvastatin (80 mg od) in patients undergoing elective cardiac surgery •Prevents shortening of the atrial effective refractory period in the postoperative period •Leads to a reduction in atrial production of reactive oxygen species and systemic markers of inflammation and cardiac function
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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 | Yes |
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) | Information not present in EudraCT |
E.7.1.1 | First administration to humans | Information not present in EudraCT |
E.7.1.2 | Bioequivalence study | Information not present in EudraCT |
E.7.1.3 | Other | Information not present in EudraCT |
E.7.1.3.1 | Other trial type description | |
E.7.2 | Therapeutic exploratory (Phase II) | Information not present in EudraCT |
E.7.3 | Therapeutic confirmatory (Phase III) | Information not present in EudraCT |
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 | Information not present in EudraCT |
E.8.1.3 | Single blind | Information not present in EudraCT |
E.8.1.4 | Double blind | Yes |
E.8.1.5 | Parallel group | Information not present in EudraCT |
E.8.1.6 | Cross over | Information not present in EudraCT |
E.8.1.7 | Other | Information not present in EudraCT |
E.8.2 | Comparator of controlled trial |
E.8.2.1 | Other medicinal product(s) | Information not present in EudraCT |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | Information not present in EudraCT |
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 | Information not present in EudraCT |
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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The date of last participant's discharge from hospital marks the end of the trial. |
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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 | 3 |
E.8.9.1 | In the Member State concerned months | 0 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 3 |
E.8.9.2 | In all countries concerned by the trial months | 0 |