E.1 Medical condition or disease under investigation |
E.1.1 | Medical condition(s) being investigated |
Perioperative cardiac events frequently complicate non-cardiac surgery resulting in significant morbidity, mortality and cost. There is no clear evidence from RCTs on how to lower perioperative cardiac risk. This a multi-centre, double-blind, randomized controlled group trial of metoprolol vs placebo in 10,000 moderate and high risk patients undergoing non-cardiac 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 |
To determine the impact of perioperative administration of metoprolol on cardiovascular events during the 30 day post-operative period in moderate and high-risk patients undergoing non-cardiac surgery. |
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E.2.2 | Secondary objectives of the trial |
Secondary objectives include an evaluation of the impact of metoprolol on long-term risk of cardiovascular events and the effect of perioperative metoprolol on length of hospital stay/ICU/CCU. |
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E.2.3 | Trial contains a sub-study | Information not present in EudraCT |
E.3 | Principal inclusion criteria |
Patients are eligible if they are undergoing non cardiac surgery; age > 45 years, have an expected length of hospital stay > 24 hours for surgical reasons, AND fulfill any one of the following six criteria: history of coronary artery disease, peripheral vascular disease, history of stroke thought due to atherothrombotic disease, hospitalization for congestive heart failure within 3 years of randomization, undergoing major vascular surgery OR fulfill any 3 of the following 7 risk factors: undergoing high-risk type surgery (intrathoracic, intraperitoneal), any history of congestive heart failure, diabetes and currently on an oral hypoglycemic agent or insulin therapy, pre-operative serum creatinine > 175 µmol/L (>2.0 mg/dl), age > 70 years, history of transient ischemic attack, undergoing emergency/urgent surgery |
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E.4 | Principal exclusion criteria |
Contraindication to metoprolol including any of the following: significant bradycardia (heart rate < 50 beats per minute); second or third degree heart block without a pacemaker; asthma that has been active within the last decade (i.e. a clinical diagnosis of asthma and use of regular inhaled steroids, or beta agonists at least once per week over the period of a month, any time in the last ten years); and a history of COPD with bronchospasm on pulmonary function tests (i.e. an increase in FEV1 > 12% and of at least 200 ml, 15 minutes after inhalation of a beta 2 – agonist). Clinical plan to use a beta-blocker preoperatively or during the first 30 postoperative days Prior adverse reaction to a beta-blocker CABG surgery with complete revascularization in the preceding 5 years and no evidence of cardiac ischemia since the CABG surgery Patients undergoing low risk surgical procedures (e.g. transurethral procedures [transurethral prostatectomies (TURPs), stone baskets, etc], ophthalmologic procedures under topical or regional anesthesia [cornea transplants, cataract surgery, etc], and surgeries with limited physiological stresses [digital re-implantation, nerve repairs, etc] ) Concurrent use of verapamil; OR Prior enrollment in this trial
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E.5 End points |
E.5.1 | Primary end point(s) |
There will be adjudication of the primary outcomes (i.e. cardiovascular death, nonfatal myocardial infarction, and nonfatal cardiac arrest) by a blinded adjudication committee. Clinical centers will therefore forward supporting documents for these outcomes. |
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E.6 and E.7 Scope of the trial |
E.6 | Scope of the trial |
E.6.1 | Diagnosis | Information not present in EudraCT |
E.6.2 | Prophylaxis | Yes |
E.6.3 | Therapy | Yes |
E.6.4 | Safety | Yes |
E.6.5 | Efficacy | Yes |
E.6.6 | Pharmacokinetic | Information not present in EudraCT |
E.6.7 | Pharmacodynamic | Yes |
E.6.8 | Bioequivalence | Information not present in EudraCT |
E.6.9 | Dose response | Information not present in EudraCT |
E.6.10 | Pharmacogenetic | Information not present in EudraCT |
E.6.11 | Pharmacogenomic | Information not present in EudraCT |
E.6.12 | Pharmacoeconomic | Information not present in EudraCT |
E.6.13 | Others | Information not present in EudraCT |
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) | No |
E.8.2.2 | Placebo | Yes |
E.8.2.3 | Other | No |
E.8.3 |
The trial involves single site in the Member State concerned
| Information not present in EudraCT |
E.8.4 | The trial involves multiple sites in the Member State concerned | Information not present in EudraCT |
E.8.5 | The trial involves multiple Member States | Yes |
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 | Information not present in EudraCT |
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 POISE study end 30 days after allocation of the last patient, i.e. patient number 10.000 world wide. See the protocol for the interim analyses and stopping rules. |
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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 | 5 |
E.8.9.2 | In all countries concerned by the trial months | 0 |