Clinical Trials Register

Summary
EudraCT Number:	2009-018173-31
Sponsor's Protocol Code Number:	POISE-2
National Competent Authority:	Denmark - DHMA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-04-29
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

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A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2009-018173-31

A.3

Full title of the trial

A large, international, placebo-controlled, factorial trial to assess the impact of low-dose clonidine and low-dose acetyl-salicylic acid (ASA) in patients undergoing noncardiac surgery who are at risk of a perioperative cardiovascular event. PeriOperative ISchemic Evaluation-2 (POISE-2) Trial

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

A.3.2

Name or abbreviated title of the trial where available

POISE-2

A.4.1

Sponsor's protocol code number

POISE-2

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Population Health Research Institute
B.1.3.4	Country	Canada
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Population Health Research Institute
B.4.2	Country	Canada
B.4.1	Name of organisation providing support	Boehringer Ingelheim
B.4.2	Country	Canada
B.4.1	Name of organisation providing support	Bayer Schering Pharma
B.4.2	Country	Germany
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Population Health Research Institute
B.5.2	Functional name of contact point	POISE-2 Project Office
B.5.3	Address:
B.5.3.1	Street Address	237 Barton Street East
B.5.3.2	Town/ city	Hamilton, Ontario
B.5.3.3	Post code	Canada L8L 2X2
B.5.3.4	Country	Canada
B.5.4	Telephone number	+1-905-527-43224047
B.5.5	Fax number	+1-905-297-3779
B.5.6	E-mail	poise2@phri.ca

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	acetyl-salicylic acid
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	acetyl-salicylic acid
D.3.9.1	CAS number	50-78-2
D.3.9.2	Current sponsor code	ASA
D.3.9.3	Other descriptive name	ACETYLSALICYLIC ACID
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100 to mg
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 2
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Clonidine
D.3.4	Pharmaceutical form	Transdermal patch
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Transdermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CLONIDINE HYDROCHLORIDE
D.3.9.1	CAS number	4205-91-8
D.3.9.2	Current sponsor code	CLONIDINE HYDROCHLORIDE
D.3.9.3	Other descriptive name	CLONIDINE HYDROCHLORIDE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No
D.IMP: 3
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	Clonidine
D.3.4	Pharmaceutical form	Tablet
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Oral use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	CLONIDINE HYDROCHLORIDE
D.3.9.1	CAS number	4205-90-7
D.3.9.2	Current sponsor code	CLONIDINE HYDROCHLORIDE
D.3.9.3	Other descriptive name	CLONIDINE HYDROCHLORIDE
D.3.10	Strength
D.3.10.1	Concentration unit	mg milligram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	0.2
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	Yes
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	No
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	No
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 2
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Tablet
D.8.4	Route of administration of the placebo	Oral use
D.8 Placebo: 3
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Transdermal patch
D.8.4	Route of administration of the placebo	Transdermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

To determine the impact of clonidine versus placebo and 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.1.1.1

Medical condition in easily understood language

To determine the impact of clonidine and ASA versus placebo on the all-cause mortality or nonfatal MI in patients with, or at risk of, atherosclerotic disease who are undergoing noncardiac surgery.

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	15.1
E.1.2	Level	PT
E.1.2	Classification code	10007649
E.1.2	Term	Cardiovascular disorder
E.1.2	System Organ Class	10007541 - Cardiac disorders

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

E.2.2

Secondary objectives of the trial

To determine the impact of clonidine and ASA on cardiovascular events at 30 days and 1 year after surgery.

E.2.3

Trial contains a sub-study

E.3

Principal 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 one or more of the following 5 criteria: A. History of coronary artery disease; B. History of peripheral vascular disease; C. History of stroke; D. Undergoing major vascular surgery; or E. Any 3 of the following 9 criteria: undergoing major surgery (i.e. intraperitoneal, retroperitoneal, intrathoracic, or major orthopedic surgery), history of congestive heart failure, transient ischemic attack, diabetes and currently taking an oral hypoglycemic agent or insulin, age > 70 years, hypertension, serum creatinine > 175 µmol/L (> 2.0 mg/dL), history of smoking within 2 years of surgery, undergoing urgent/emergent surgery

E.4

Principal exclusion 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 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; 10. Bare-metal coronary stent in the 6 weeks prior to randomization; 11. Having taken 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 currently taking an alpha-2 agonist, alpha methyldopa, monoamine oxidase inhibitors or reserpine; 12. Planned use – during the first 3 days after surgery – therapeutic dose anticoagulation or a therapeutic subcutaneous or intravenous antithrombotic agent; 13. Undergoing intracranial surgery, carotid endarterectomy, or retinal surgery; 14. Is pregnant or do not wish to use means of antikonception in the intervention period 15. Not consenting to participate in POISE-2 prior to surgery; 16. Previously enrolled in POISE-2 Trial

E.5 End points

E.5.1

Primary end point(s)

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.5.1.1

Timepoint(s) of evaluation of this end point

30 days and 1 year

E.5.2

Secondary end point(s)

Cardiovascular death, non-fatal myocardial infarction, non-fatal cardiac arrest, cardiac re-vascularisation procedure, pulmonary embolus, deep venous thrombosis, clinical important atrial flutter, amputation, peripheral arterial thrombosis, infection/sepsis, re-admission for cardiovascular reasons, length of stay in hospital, length of stay in intensive care unit / cardiologic intensive care (ICU/CCU) – and new kidney failure needing dialysis.

E.5.2.1

Timepoint(s) of evaluation of this end point

30 days and one year after randomisation

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.3

Single blind

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

Factorial

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

Yes

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

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

E.8.5

The trial involves multiple Member States

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Australia

Austria

Belgium

Brazil

Canada

Colombia

Denmark

India

Spain

United States

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

The study will be finished one year after the inclusion of the last patient.

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1