Clinical Trials Register

Summary
EudraCT Number:	2010-020677-17
Sponsor's Protocol Code Number:	ALMED-09-C3-026
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-06-29
Trial results	View 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

Germany - BfArM

A.2

EudraCT number

2010-020677-17

A.3

Full title of the trial

Efficacy and safety of xenon anaesthesia compared to sevoflurane
anaesthesia and total intravenous anaesthesia for on-pump coronary
artery bypass graft surgery: a randomised, three-arm, single-blind,
international study.

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

Xenon in Cardiac Surgery

A.4.1

Sponsor's protocol code number

ALMED-09-C3-026

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	Air Liquide Santé International
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Air Liquide Santé International
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Air Liquide Santé International
B.5.2	Functional name of contact point	Vice President Medical
B.5.3	Address:
B.5.3.1	Street Address	75 Quai d'Orsay
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75007
B.5.3.4	Country	France
B.5.4	Telephone number	+33(0)139 07 63 42
B.5.5	Fax number	+33(0)139 07 61 99
B.5.6	E-mail	juan-fernando.ramirez@airliquide.com

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.2.1.1.1	Trade name	LENOXe
D.2.1.1.2	Name of the Marketing Authorisation holder	AIR LIQUIDE Santé International
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	Xenon
D.3.4	Pharmaceutical form	Medicinal gas, liquefied
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	007440-63-3
D.3.9.3	Other descriptive name	XENON
D.3.9.4	EV Substance Code	SUB32179
D.3.10	Strength
D.3.10.1	Concentration unit	% (V/V) percent volume/volume
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
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	Comparator
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	Sevoflurane
D.3.4	Pharmaceutical form	Inhalation vapour, liquid
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Inhalation use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	SEVOFLURANE
D.3.9.1	CAS number	28523-86-6
D.3.9.3	Other descriptive name	SEVOFLURANE
D.3.9.4	EV Substance Code	SUB10506MIG
D.3.10	Strength
D.3.10.1	Concentration unit	% percent
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1.8
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	Comparator
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	Propofol
D.3.4	Pharmaceutical form	Emulsion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intravenous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.1	CAS number	2078-54-8
D.3.9.3	Other descriptive name	PROPOFOL
D.3.9.4	EV Substance Code	SUB10116MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/kg milligram(s)/kilogram
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2-4
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

General anesthesia for on pump coronary artery bypass surgery

E.1.1.1

Medical condition in easily understood language

anaesthesia for bypass surgery

E.1.1.2

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Anesthesia and Analgesia [E03]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.0
E.1.2	Level	LLT
E.1.2	Classification code	10006894
E.1.2	Term	CABG
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To assess the effect of xenon anesthesia on the posteoperative blood
level of cardiac troponin, a predictive marker of medium and long term
clinical outcome after coronary artery bypass graft surgery 24 hours
after the end of intervention, compared to sevoflurane anesthesia and
total intravenous anesthesia.

E.2.2

Secondary objectives of the trial

- To assess the effect of xenon on other myocardial damage-related
criteria and on short term consequences of myocardial damage
- To assess the feasbility of xenon for cornoary artery bypass graft
surgery
- To assess the effect of xenon of the postoperative follow-up, during
intensive care unit stay and hospital saty
- To assess the effect of xenon on the incidence of posteperative delirium
-To assess the effect of xenon on safety

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1)Male or female patients aged 18 years (or having reached majority if
the legal age of majority is over 18) or more at the date of selection
2)Coronary heart disease requiring elective isolated coronary artery
bypass graft surgery to be performed with cardiopulmonary bypass in
mild hypothermia (central temperature between 32° and 34° Celsius) or
normothermia with cardiac arrest and cold or warm cardioplegia
3)Normal or moderately impaired left ventricular systolic function
(corresponding to a left ventricular ejection fraction above or equal to
35%, if available)
4)Written informed consent signed and dated by the patient after full
explanation of the study has been given by the investigator prior to
participation

E.4

Principal exclusion criteria

-Legal incapacity or limited legal capacity
- Women who are pregnant, breast-feeding or women of childbearing
potential not using adequate contraceptive methods
- Patient previously randomised in this study
- Recent acute myocardial infarction (within 7 days)
- Ongoing unstable angina
- Active endocarditis
- Ongoing treatment with nicorandil
- Ongoing treatment with a sulfonylurea medication if this treatment
cannot be replaced 24 hours before surgery
- Participation in a drug or device trial within the previous 30 days
- Known contraindication to xenon, sevoflurane, propofol or sufentanil
- Recent or ongoing myocardial damage/infraction with cardiac troponin
level assessed within 24 hours of surgery above the upper reference
limite for the diagnosis of mycocardial infraction (local laboratory) or
prolonged thoracic pain and ST-segement deviation at rest
- Severe renal dysfunction with preoperative value of serum creatinine
level above 200 micromoles/litre(local laboratory)
- Severe haptic dysfunction with preoperative value of alanine aminetransferase
or alkaline phosphatase three times above the upper normal
value(loval laboratory)
- Severely depressed left ventricular function, corresponding to an
ejection fraction below 35%,if available

E.5 End points

E.5.1

Primary end point(s)

Cardiac troponin blood level measured 24 hours after the end of
intervention (central laboratory)

E.5.1.1

Timepoint(s) of evaluation of this end point

This time point is the most frequently chosen time point reported in
studies performed to investigate the correlation between troponin levels
and clinical outcome.

E.5.2

Secondary end point(s)

Other myocardial damage ( blood cardiac troponin, CK-MB levels, MI
type 5 , NT-proBNP levels, CRP levels),feasibility of xenon as anaesthetic
during CABG, ICU parameters(blood loss, blood transfusion, length of
stay) mechamical ventilation , incidence on post operative delirium
(CAM test), safety (Adverse event)

E.5.2.1

Timepoint(s) of evaluation of this end point

From the inclusion to the hospital discharge. During anaesthesia, 12
hours, 24hours, 48 hours, at the ICU discharge, at the hospital
discharge. For CAM test, at inclusion then once a day as soon as trachea
is extubated, at the ICU discharge and Hospital discharge

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

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)

Yes

E.7.4

Therapeutic use (Phase IV)

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

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Sevoflurane(PR2),Propofol(PR3)

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

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

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 LAST SUBJECT

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.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

412

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

Yes

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

190

F.4.2

For a multinational trial

F.4.2.1

In the EEA

509

F.4.2.2

In the whole clinical trial

509

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)

Normal treatment of that condition will be received by the patient after
his/her participation.

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2011-08-29

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-10-20

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2014-04-05

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