E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perioperative atrial fibrillation/atrial flutter after major noncardiac thoracic surgery. Myocardial injury after noncardiac surgery. |
|
E.1.1.1 | Medical condition in easily understood language |
Fast irregular heartbeats after thoracic surgery. Abnormal troponin elevations. |
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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 | PT |
E.1.2 | Classification code | 10003662 |
E.1.2 | Term | Atrial flutter |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 20.0 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10003658 |
E.1.2 | Term | Atrial fibrillation |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
E.1.2 Medical condition or disease under investigation |
E.1.2 | Version | 24.1 |
E.1.2 | Level | PT |
E.1.2 | Classification code | 10085879 |
E.1.2 | Term | Myocardial injury |
E.1.2 | System Organ Class | 10007541 - Cardiac disorders |
|
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 |
The co-primary objectives of the trial are to determine whether the administration of colchicine compared with placebo reduces the occurrence of perioperative atrial fibrillation/atrial flutter, and myocardial injury after noncardiac surgery within 14 days of randomization. |
|
E.2.2 | Secondary objectives of the trial |
The secondary objectives of the trial are to determine whether the administration of colchicine compared with placebo reduces the following within 14 days of randomization: 1. first occurrence of the composite of all-cause mortality, nonfatal MINS, or nonfatal stroke; 2. first occurrence of the composite of all-cause mortality, nonfatal myocardial infarction (MI), or nonfatal stroke; 3. MINS not fulfilling the 4th universal definition of MI; 4. MI; 5. time to chest tube removal; and 6. duration of stay in ICU, step-down, and in-hospital. |
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Patients are eligible if they: 1. are undergoing thoracic surgery with general anesthesia; 2. are ≥55 years of age at the time of randomization; 3. are expected to require at least an overnight hospital admission after surgery; and 4. provide written informed consent to participate. |
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E.4 | Principal exclusion criteria |
Patients are excluded if they: 1. have a prior history of documented AF; 2. are currently taking anti-arrhythmic medication; 3. are undergoing minor thoracic interventions/procedures; 4. have contraindications to colchicine; 5. are not expected to take oral medications for >24 hours after surgery; 6. are scheduled for lung transplantation; 7. are currently taking non-study colchicine before surgery; 8. have severe hepatic dysfunction; 9. have aplastic anemia; 10. women of childbearing potential who are not taking effective contraception, pregnant or breast-feeding; 11. took within the last 14 days or scheduled to take during the first 10 days after surgery clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole or itraconazole; 12. HIV patients treated with antiretroviral therapy; or 13. are scheduled for thoracoscopic wedge resection only. |
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E.5 End points |
E.5.1 | Primary end point(s) |
1. Clinically important perioperative atrial fibrillation/atrial flutter 2. Myocardial injury after noncardiac surgery |
|
E.5.1.1 | Timepoint(s) of evaluation of this end point |
14 days after randomization |
|
E.5.2 | Secondary end point(s) |
1. First occurrence of the composite of all-cause mortality, nonfatal myocardial infarction, or nonfatal stroke 2. Number of days alive and at home 3. Time to chest tube removal 4. Duration of stay in ICU, step-down, and in-hospital 5. All-cause mortality 6. Occurrence of myocardial infarction
|
|
E.5.2.1 | Timepoint(s) of evaluation of this end point |
14 days after randomization |
|
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) | 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) | Yes |
E.7.4 | Therapeutic use (Phase IV) | No |
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 | Yes |
E.8.1.5 | Parallel group | Yes |
E.8.1.6 | Cross over | No |
E.8.1.7 | Other | No |
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 | No |
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
| No |
E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
E.8.5 | The trial involves multiple Member States | Yes |
E.8.5.1 | Number of sites anticipated in the EEA | 17 |
E.8.6 Trial involving sites outside the EEA |
E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | No |
E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
Colombia |
Malaysia |
Switzerland |
Hong Kong |
Canada |
Pakistan |
United States |
Austria |
Belgium |
Italy |
Spain |
|
E.8.7 | Trial has a data monitoring committee | Yes |
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
|
|
E.8.9 Initial estimate of the duration of the trial |
E.8.9.1 | In the Member State concerned years | 1 |
E.8.9.1 | In the Member State concerned months | 6 |
E.8.9.1 | In the Member State concerned days | |
E.8.9.2 | In all countries concerned by the trial years | 1 |