Clinical Trials Register

Summary
EudraCT Number:	2010-023839-42
Sponsor's Protocol Code Number:	H8O-CY-O027
National Competent Authority:	Czechia - SUKL
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2011-01-26
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

Czechia - SUKL

A.2

EudraCT number

2010-023839-42

A.3

Full title of the trial

EXEnatide in patients undergoing Coronary artery bypass grafting for improved glUcose conTrol and hemodynamIc ValuEs

A.3.1

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

Assessment of glycemic compensation and hemodynamic parameteres in patients after administration of GLP-1 agonist exenatid during and after the implantation of aortocoronary by-pass.

A.3.2

Name or abbreviated title of the trial where available

EXECUTIVE

A.4.1

Sponsor's protocol code number

H8O-CY-O027

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	General University Hospital in Prague
B.1.3.4	Country	Czech Republic
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	Eli Lilly
B.4.2	Country	Czech Republic
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	General University Hospital and Charles University in Prague
B.5.2	Functional name of contact point	3rd Department of Medicine
B.5.3	Address:
B.5.3.1	Street Address	U nemocnice 1
B.5.3.2	Town/ city	Prague 2
B.5.3.3	Post code	12808
B.5.3.4	Country	Czech Republic
B.5.4	Telephone number	+420224 96 66 94
B.5.5	Fax number	+420224 91 97 80
B.5.6	E-mail	milos_mraz@yahoo.co.uk

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	Byetta
D.2.1.1.2	Name of the Marketing Authorisation holder	Eli Lilly Nederland, B.V.
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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.3.4	Pharmaceutical form	Solution 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.3.8	INN - Proposed INN	EXENATIDE
D.3.9.1	CAS number	141758-74-9
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10
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

Patients with elective coronary artery bypass grafting with LV systolic dysfunction (EF LV ≤ 50%)

E.1.1.1

Medical condition in easily understood language

Patients with dysfunction of the left heart ventricle undergoing planned coronary artery bypass implantation

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	14.1
E.1.2	Level	PT
E.1.2	Classification code	10011077
E.1.2	Term	Coronary artery bypass
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	HLT
E.1.2	Classification code	10012602
E.1.2	Term	Diabetes mellitus (incl subtypes)
E.1.2	System Organ Class	10014698 - Endocrine 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

To examine whether pre- and peri-operative administration of exenatide affects perioperative hemodynamics,
echocardiographic parameters, necessity of antiarrhytmic and inotropic treatment and glucose control after
CABG operation.

E.2.2

Secondary objectives of the trial

To examine safety and tolerability of peri-operative administration of exenatide in type 2 diabetic patients
undergoing coronary artery bypass grafting operation (CABG).

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

- elective coronary artery bypass grafting operation (CABG) and/or valvuloplasty
- LV systolic dysfunction (EF LV ≤ 50%)
- Age 18 - 85 years
- Signed informed consent
- Females with childbearing potential have to use appropriate contraceptive measures during the whole study period and 6 months after terminating exenatide infusion (hormonal contraception or double-barrier contraception for both partners)

E.4

Principal exclusion criteria

- allergy to exenatide
- allergy to insulin
- mental incapacity or language barrier
- use of incretin-based therapies <3 months before inclusion in the study
- established autonomic neuropathy
- history of acute pancreatitis or severe disease of digestive tract
- renal failure (preoperative creatinine ≥ 180 umol/l)
- liver failure (coagulation times more than 1.5 times higher without use of anticoagulants)
- cardiac surgical procedure on valve, thoracic aorta or MAZE procedure
- diabetic ketoacidosis
- pregnancy and lactation

E.5 End points

E.5.1

Primary end point(s)

A: Echocardiographic parameters:
- cardiac chamber dimensions (including left ventricle, left atrium, right atrium and right ventricle)
- left ventricular systolic function - ejection fraction of left ventricular (%) with the use of the Simpson’s method
on standard 2-dimensional images, RWMA (regional wall motion abnormalities) according to 4 degrees
system and WMSI (wall motion score index) with the use of the 16-segment model of the American Society of
Echocardiography, VTI (measured in left ventricular outflow tract)
- left ventricular diastolic function - transmitral inflow early filling peak velocity (E), atrial peak velocity (A),
E/A ratio and deceleration time (DTE), pulmonary vein flow (or hepatic vein flow), Doppler tissue imaging of
mitral annular motion (E/e‘)
- right ventricular systolic function - with the use of TAPSE (tricuspid anulus plane systolic excursion)

B. perioperative hemodynamics (messured by Swan-Ganz catheter)
Postoperatively every 3 (for first 24 hours) and 6 hours (for another 24-48 h)
- cardiac output and index
- stroke volume
- mean arterial pressure
- pulmonary artery pressures)
- heart rate

C: Antiarrhytmic treatment
- need for antiarhytmic Tx – No of patients and total dose of amiodarone
- need for temporary pacing

D: Dose of inotropic drugs
- total dose of inotropes for each patient and total time (in hours) of infusion (preferable dobutamine or milrinone
if necessary)
- total dose of vasopressors and total time of infusion (norepinephrine)
(indication for inotropes (dobutamin first choice) to keep CI over 2.4 l//min/m2, to keep HR (heart rate ) below
110/min. indication for vasopressors (norepinephrin) to keep mean arterial pressure between 65-80mmHg
according to preoperative BP and comorbidities)

E: Glucose control (time to the target range, time within the target range, time above the target range, frequency
of hypoglycemia, total insulin dose)

E.5.1.1

Timepoint(s) of evaluation of this end point

72 hours after the beginning of exenatide administration

E.5.2

Secondary end point(s)

- tolerability of exenatide
- safety (side effects)
- troponin I levels first postoperative day,
- trends, medians or means of lactate, SvO2 (PAC), number of ischaemic events (according to ECG ST analysis),
- exploratory endpoints (biomarkers of inflammation (e.g. CRP), adipokines etc.)

E.5.2.1

Timepoint(s) of evaluation of this end point

90 days after the beginning of exenatid administration

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

Yes

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

Yes

E.8.1.3

Single blind

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

no substance

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

Yes

E.8.4

The trial involves multiple sites in the Member State concerned

E.8.5

The trial involves multiple Member States

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 subject last visit

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:

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

F.3.3.1

Women of childbearing potential not using contraception