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    The EU Clinical Trials Register currently displays   43916   clinical trials with a EudraCT protocol, of which   7306   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

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    Summary
    EudraCT Number:2009-018173-31
    Sponsor's Protocol Code Number:
    National Competent Authority:UK - MHRA
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2011-05-19
    Trial results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedUK - MHRA
    A.2EudraCT number2009-018173-31
    A.3Full title of the trial
    A large, international, placebo-controlled, factorial trial to assess the impact of low-dose clonidine and acetyl-salicyclic acid (ASA) in patients undergoing noncardiac surgery who are at risk of a perioperative cardiovascular event. PeriOperative ISchemic Evaluation-2 Trial.
    A.3.2Name or abbreviated title of the trial where available
    PeriOperative ISchemic Evaluation-2 Trial
    A.4.1Sponsor's protocol code number
    A.5.1ISRCTN (International Standard Randomised Controlled Trial) NumberISRCTN17233551
    A.7Trial is part of a Paediatric Investigation Plan Information not present in EudraCT
    A.8EMA Decision number of Paediatric Investigation Plan
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorPopulation Health Research Institute
    B.1.3.4CountryCanada
    B.3.1 and B.3.2Status of the sponsorNon-Commercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing support
    B.4.2Country
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisation
    B.5.2Functional name of contact point
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameAspirin® protect 100 mg
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNacetylsalicylic acid
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 2
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Catapres Tablets 100 micrograms
    D.2.1.1.2Name of the Marketing Authorisation holderBoehringer Ingelheim Limited
    D.2.1.2Country which granted the Marketing AuthorisationUnited Kingdom
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCatapres Tablets 100 micrograms
    D.3.4Pharmaceutical form Tablet
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNclonidine hydrochloride
    D.3.10 Strength
    D.3.10.1Concentration unit µg microgram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number100microgram
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.IMP: 3
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation Yes
    D.2.1.1.1Trade name Catapres-TTS
    D.2.1.1.2Name of the Marketing Authorisation holderBOEHRINGER INGELHEIM ITALIA S.p.A
    D.2.1.2Country which granted the Marketing AuthorisationItaly
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community No
    D.2.5.1Orphan drug designation number
    D.3 Description of the IMP
    D.3.1Product nameCATAPRESAN TTS-2
    D.3.4Pharmaceutical form Transdermal patch
    D.3.4.1Specific paediatric formulation Information not present in EudraCT
    D.3.7Routes of administration for this IMPTransdermal use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNClonidine Hydrochloride
    D.3.10 Strength
    D.3.10.1Concentration unit mg milligram(s)
    D.3.10.2Concentration typeequal
    D.3.10.3Concentration number5
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) Information not present in EudraCT
    D.3.11.3.1Somatic cell therapy medicinal product Information not present in EudraCT
    D.3.11.3.2Gene therapy medical product Information not present in EudraCT
    D.3.11.3.3Tissue Engineered Product Information not present in EudraCT
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) Information not present in EudraCT
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product Information not present in EudraCT
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy Information not present in EudraCT
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product Information not present in EudraCT
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTablet
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 2
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboCapsule
    D.8.4Route of administration of the placeboOral use
    D.8 Placebo: 3
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboTransdermal patch
    D.8.4Route of administration of the placeboTransdermal use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    Patients at risk of Peri operative associated cardiovascular events
    MedDRA Classification
    E.1.3Condition being studied is a rare disease No
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    What is the effect of low-dose clonidine versus placebo and low-dose ASA versus placebo on the 30-day risk of all-cause mortality or nonfatal MI in patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery?
    E.2.2Secondary objectives of the trial
    1. To determine the impact of perioperative administration of low-dose clonidine and separately low-dose ASA on each of the following individual secondary outcomes at 30 days after randomization: all-cause mortality, vascular mortality, MI, nonfatal cardiac arrest, cardiac revascularization procedure, pulmonary emboli, deep venous thrombosis, clinically important atrial fibrillation, rehospitalization for vascular reasons, length of hospital stay, length of intensive care unit / cardiac care unit (ICU/CCU) stay, and new acute renal failure requiring dialysis. 2. To determine the impact of perioperative administration of low-dose clonidine and separately low-dose ASA on the composite of all-cause mortality, nonfatal MI, and nonfatal stroke at 30 days after randomization. 3. To determine in each ASA stratum the impact on a composite outcome of all-cause mortality, nonfatal MI, cardiac revascularization procedure, nonfatal pulmonary emboli, and nonfatal deep venous thrombosis at 30 da
    E.2.3Trial contains a sub-study Yes
    E.3Principal inclusion criteria
    1. are undergoing noncardiac surgery; 2. are ≥ 45 years of age; 3. are expected to require at least an overnight hospital admission after surgery; AND 4. fulfill > 1 of the following 5 criteria: A. history of coronary artery disease as defined by any one of the following 6 criteria i. history of angina ii. history of a myocardial infarction or acute coronary syndrome iii. history of a segmental cardiac wall motion abnormality on echocardiography or a segmental fixed defect on radionuclide imaging iv. history of a positive radionuclide exercise, echocardiographic exercise, or pharmacological cardiovascular stress test demonstrating cardiac ischemia v. history of a coronary angiographic or CT coronary angiographic evidence of atherosclerotic stenosis ≥ 50% of the diameter of any coronary artery vi. ECG with pathological Q waves in two contiguous leads POISE-2 Trial Version 4 March 1, 2010April 6, 2011 13 vii. previous coronary artery revascularization, i.e. percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) B. history of peripheral vascular disease as defined by a physician diagnosis of a current or prior history of any one of the following 4 criteria i. intermittent claudication ii. vascular surgery for atherosclerotic disease iii. an ankle/arm systolic blood pressure ratio < 0.90 in either leg at rest iv. angiographic or doppler study demonstrating > 70% stenosis in a noncardiac artery C. history of stroke as defined by any one of the following 2 criteria i. a physician diagnosis of stroke ii. CT or MRI evidence of a prior stroke D. undergoing major vascular surgery defined as all vascular surgery except arteriovenous shunt, vein stripping procedures, and carotid endarterectomies;, and endovascular abdominal aortic aneurysm repair (EVAR); OR E. any 3 of 9 risk criteria i. undergoing major surgery defined as intraperitoneal, intrathoracic, retroperitoneal or major orthopedic surgery (i.e., hip arthroplasty, internal fixation of hip or femur, pelvic arthroplasty, knee arthroplasty, above-knee amputation or amputation below the knee but above the foot) ii. history of congestive heart failure defined as a physician diagnosis of a current or prior episode of congestive heart failure OR prior radiographic evidence of vascular redistribution, interstitial pulmonary edema, or frank alveolar pulmonary edema iii. history of a transient ischemic attack; iv. diabetes and currently taking an oral hypoglycemic agent or insulin; v. age > 70 years; vi. hypertension; vii. serum creatinine > 175 ╬╝mol/L (> 2.0 mg/dl); viii. history of smoking within 2 years of surgery; ix. undergoing emergent/urgent surgery defined as surgery that a surgeon schedules to go to the operating room within 48 hours of an acute presentation to the hospital
    E.4Principal exclusion criteria
    We will exclude patients meeting any of the following criteria: 1. consumption of ASA within 72 hours prior to surgery; 2. hypersensitivity or known allergy to ASA or clonidine; 3. systolic blood pressure < 105 mm Hg; 4. heart rate < 55 beats per minute in a patient who does not have a permanent pacemaker; 5. second or third degree heart block without a permanent pacemaker; 6. active peptic ulcer disease or gastrointestinal bleeding within previous 6 weeks; 7. intracranial hemorrhage (including subdural hematoma and parenchymal hematoma as a complication of primary ischemic stroke) documented by neuro-imaging, in the 6 months prior to randomization. This does not include petechial hemorrhagic transformation of a primary ischemic stroke; 8. subarachnoid hemorrhage or epidural hematoma unless the event occurred more than 6 months prior to randomization and the offending aneurysm or arterial lesion has been repaired; 9. drug-eluting coronary stent in the year prior to randomization;96 10. bare-metal coronary stent in the 6 weeks prior to randomization;96 11. thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel) or ticagrelor within 72 hours prior to surgery; or intent to restart a thienopyridine or ticagrelor during the first 7 days post-op; or POISE-2 Trial Version 4 March 1, 2010April 6, 2011 14 currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine, ticagrelor, or thienopyridine (e.g., clopidogrel, ticlopidine, prasugrel);; 12. planned use – during the first 3 days after surgery – therapeutic dose anticoagulation (e.g., warfarin with a target INR > 2.0, dabigatran > 250 mg/day, or rivaroxaban > 10 mg/day) or a therapeutic subcutaneous or intravenous antithrombotic agent (defined as full dose unfractionated heparin [i.e., > 15, 000 u/24hrs], low molecular weight heparin [i.e., > 6,000 u/24hrs or enoxaparin: > 60 mg/24hrs], or fondaparinux [i.e., > 2.5mg/24hrs]; 13. undergoing intracranial surgery, carotid endarterectomy, or retinal surgery; 14. not consenting to participate in POISE-2 prior to surgery; OR 15. previously enrolled in POISE-2 Trial
    E.5 End points
    E.5.1Primary end point(s)
    The overall primary outcome of the POISE-2 Trial is a composite of all-cause mortality and nonfatal MI at 30 days after randomization. We will present the time-to-the first occurrence of one of the components of the primary outcome using the Kaplan-Meier estimator. We will use log-rank tests to compare the rate of occurrence of the primary outcome between the ASA versus ASA placebo group and separately the clonidine versus the clonidine placebo group. We will use Cox proportional hazards models to estimate the effect of clonidine, and of ASA, on the hazard ratio for the primary and secondary outcomes (with stratification according to whether treatment included the other agent). We will calculate the hazard ratios and their associated 95% confidence intervals. We will infer statistical significance if the computed 2-sided p-value is < 0.05. We anticipate that the treatment effect of clonidine and ASA, if present, will act independently, but we will, however, evaluate the possibility of synergism or antagonism by formally testing the interaction term in a Cox model.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis Yes
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic No
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response No
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans Information not present in EudraCT
    E.7.1.2Bioequivalence study Information not present in EudraCT
    E.7.1.3Other Information not present in EudraCT
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open Information not present in EudraCT
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group No
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) Yes
    E.8.2.2Placebo Yes
    E.8.2.3Other Information not present in EudraCT
    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.8.4.1Number of sites anticipated in Member State concerned10
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA50
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA Information not present in EudraCT
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    E.8.7Trial 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
    last visit of the last subject undergoing the trial where he/she would be follow-up for a year.
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years3
    E.8.9.1In the Member State concerned months
    E.8.9.1In the Member State concerned days
    E.8.9.2In all countries concerned by the trial years3
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 No
    F.1.1.1In Utero Information not present in EudraCT
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) Information not present in EudraCT
    F.1.1.3Newborns (0-27 days) Information not present in EudraCT
    F.1.1.4Infants and toddlers (28 days-23 months) Information not present in EudraCT
    F.1.1.5Children (2-11years) Information not present in EudraCT
    F.1.1.6Adolescents (12-17 years) Information not present in EudraCT
    F.1.2Adults (18-64 years) Yes
    F.1.3Elderly (>=65 years) Yes
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations No
    F.3.3.1Women of childbearing potential not using contraception Information not present in EudraCT
    F.3.3.2Women of child-bearing potential using contraception Information not present in EudraCT
    F.3.3.3Pregnant women Information not present in EudraCT
    F.3.3.4Nursing women Information not present in EudraCT
    F.3.3.5Emergency situation Information not present in EudraCT
    F.3.3.6Subjects incapable of giving consent personally Information not present in EudraCT
    F.3.3.7Others Information not present in EudraCT
    F.4 Planned number of subjects to be included
    F.4.1In the member state2000
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 5000
    F.4.2.2In the whole clinical trial 10000
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    There is no arrangements are made or available for drug or procedure intervention, once the research has finished. All patients would receive normal care from NHS as part of their disease management. If there is any issue that might happen after research completion, those research participants would be managed appropriately as those who would have had a normal care.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2011-07-11
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2011-04-15
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2015-03-17
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