E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
The study investigates standard anaesthesia for surgery. There is no single specific 'disease' rather there is a population of patients requiring anaesthesia to permit surgery. |
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MedDRA Classification |
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 |
Are patients who receive nitrous oxide as a part of their anaesthetic more likely die or to experience cardiovascular events?
The primary endpoint is a composite of death and cardiovascular events (clinical and silent MI, cardiac arrest, pulmonary embolism, and stroke) measured at 30 days after surgery. |
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E.2.2 | Secondary objectives of the trial |
Are any of the following secondary endpoints in creased amongst patients receiving nitrous oxide? 1. Myocardial Infarction (MI) 2. Cardiac arrest 3. Pulmonary embolism 4. Stroke 5. Wound infection 6. Severe PONV 7. ICU Stay 8. Hospital Stay
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E.2.3 | Trial contains a sub-study | No |
E.3 | Principal inclusion criteria |
Inclusion Criteria 1. Adult males and females age ≥ 45 years, undergoing noncardiac surgery and general anaesthesia expected to exceed two hours. 2. At increased risk of cardiac events, defined as any of a) history of coronary artery disease as defined by a history of any one of the following: i. angina ii. MI iii. segmental wall motion abnormality on echocardiography or a fixed defect on radionuclide imaging iv. a positive exercise stress test for cardiac ischaemia v. a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test for cardiac ischaemia vi. coronary revascularization (CABG or PTCA) vii. angiographic evidence of atherosclerotic stenosis > 50% of the diameter of any coronary artery viii. ECG with pathological Q waves in two contiguous leads
b) heart failure c) cerebrovascular disease thought due to atherothrombotic disease d) aortic or peripheral vascular disease e) or three or more of the following risk factors: age ≥70 years any history of congestive heart failure diabetes and currently on an oral hypoglycaemic agent or insulin therapy current treatment for hypertension preoperative serum creatinine >175 mol/L (> 2.0 mg/dl) current or previous high cholesterol ≥6.2 mmol/L (> 240 mg/dl) history of a transient ischemic attack (TIA) (i.e. a transient focal neurological deficit that lasted less than 24 hours and thought to be vascular in origin) emergency/urgent surgery (i.e. surgery which must be undertaken within 24 hours of acute presentation to hospital) high-risk type of surgery (i.e. intrathoracic or intraperitoneal)
Exclusion Criteria 1. having cardiac surgery 2. marked impairment of gas-exchange expected to require Fi02> 0.5 intraoperatively 3. specific circumstances where N2O is contraindicated (eg. volvulus, pulmonary hypertension, raised intracranial pressure) or the anaesthetist plans to use supplemental oxygen (eg. colorectal surgery) 4. N2O unavailable for use.
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E.4 | Principal exclusion criteria |
Cardiac surgery, under 45 years, nitrous oxide not clinically appropriate for type of suyrgery (EG middle ear operation etc) |
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E.5 End points |
E.5.1 | Primary end point(s) |
Primary Endpoint The primary endpoint is a composite of death and cardiovascular events (clinical and silent MI, cardiac arrest, pulmonary embolism, and stroke) measured at 30 days after surgery.
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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 | No |
E.6.3 | Therapy | Yes |
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 | 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) | 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 | Yes |
E.8.1.4 | Double blind | No |
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 | No |
E.8.2.3 | Other | Yes |
E.8.2.3.1 | Comparator description |
air+oxygen will be compared with nitrous oxide+oxygen |
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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 | 11 |
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 | Yes |
E.8.6.2 | Trial being conducted completely outside of the EEA | Information not present in EudraCT |
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 |
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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
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the last visit of the last subject undergoing 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 | 0 |
E.8.9.2 | In all countries concerned by the trial years | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |
E.8.9.2 | In all countries concerned by the trial days | 0 |