Clinical Trials Register

Summary
EudraCT Number:	2014-002440-41
Sponsor's Protocol Code Number:	CO-ILEPSS
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:	2014-07-02
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

Expand All Collapse All

A. Protocol Information

A.1

Member State Concerned

Denmark - DHMA

A.2

EudraCT number

2014-002440-41

A.3

Full title of the trial

Safety and efficacy of iloprost and eptifibatide co-administration compared to standard therapy in patients with septic shock – a randomized, controlled, double-blind investigator-initiated 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

CO-ILEPSS

A.4.1

Sponsor's protocol code number

CO-ILEPSS

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	Rigshospitalet, Capital Region Bloodbank 2034, Section for Transfusion Medicine
B.1.3.4	Country	Denmark
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	Rigshospitalet
B.4.2	Country	Denmark
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Rigshospitalet, Capital Region Bloodbank 2034, Section for Transfusion Medicine
B.5.2	Functional name of contact point	Sponsor (Sisse Ostrowski)
B.5.3	Address:
B.5.3.1	Street Address	Blegdamsvej 9
B.5.3.2	Town/ city	Copenhagen Ø
B.5.3.3	Post code	2100
B.5.3.4	Country	Denmark
B.5.4	Telephone number	004524430464
B.5.5	Fax number	004535390038
B.5.6	E-mail	sisse.ostrowski@gmail.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	INTEGRILIN 2 mg/ml infusionsvæske, opløsning
D.2.1.1.2	Name of the Marketing Authorisation holder	Glaxo Group Ltd
D.2.1.2	Country which granted the Marketing Authorisation	Denmark
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	Infusion
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	EPTIFIBATIDE
D.3.9.1	CAS number	188627-80-7
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB12498MIG
D.3.10	Strength
D.3.10.1	Concentration unit	mg/ml milligram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	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: 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.2.1.1.1	Trade name	ILOMEDIN, Concentrate for infusion
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Schering Pharma
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	Concentrate for solution for infusion
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	ILOPROST TROMETAMOL
D.3.9.1	CAS number	0
D.3.9.2	Current sponsor code	NA
D.3.9.4	EV Substance Code	SUB14185MIG
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	27
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	Solution for infusion
D.8.4	Route of administration of the placebo	Intravenous use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Septic shock

E.1.1.1

Medical condition in easily understood language

Blood poisoning

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	PT
E.1.2	Classification code	10040070
E.1.2	Term	Septic shock
E.1.2	System Organ Class	10021881 - Infections and infestations

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Evaluating the safety and efficacy of iloprost and eptifibatide co-administration compared to placebo as an addition to standard care in septic shock patients.

E.2.2

Secondary objectives of the trial

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Adult intensive care patients (age ≥18 years)
AND
2. Sepsis, defined as suspected or confirmed site of infection or positive blood culture and ≥2 of 4 systemic inflammatory response syndrome (SIRS) criteria fulfilled within the last 24h:
a) Temperature ≤ 36˚ C or ≥ 38˚C
b) Heart rate ≥ 90 beats per minute
c) Mechanical ventilation for acute respiratory process or respiratory rate ≥ 20 breaths per min or PaCO2 < 4.2kPa
d) WBC ≥ 12,000/mm³ OR ≤ 4,000/mm³ OR > 10% bands
AND
3. Septic shock within the last 24h, defined as:
a. Hypotension (MAP <70 mmHg, Lactate 4 mmol/L) despite ongoing resuscitation with fluids (crystalloids, colloids, blood products) within the last 24h OR
b. ≥30 ml/kg ideal body weight (IBW) fluid (crystalloids, colloids, blood products) given in the last 24h AND
c. Need for vasopressor/inotropic agents (noradrenaline, adrenaline, dopamine) within the last 24h
AND
4. Can be randomized into trial and dosed < 24 hours after septic shock diagnosis (the time-point for the septic shock diagnosis corresponds to the time-point where the vasopressor/inotropic therapy (3c) is initiated)
AND
5. Consent is obtainable

E.4

Principal exclusion criteria

1. Patient is pregnant or breast-feeding
2. Patient weights more than 125 kg
3. Patients with known allergy towards any of the investigational products or contraindications which
should be excluded according to the investigational product specifications
4. Patients in whom the clinician finds antithrombotic therapy contraindicated - prophylaxis included
5. Patients at increased risk of bleeding:
a. Surgery in the previous 48 hours and expected surgery within 48 hours
b. Epidural or spinal puncture in the previous 12 hours
c. Platelet count less than 10,000/mm3 in the previous 24 hours
d. Need of blood products for bleeding in the previous 24 hours (3 or more RBC/24 h)
e. Treatment with any antithrombotics within 12 hours (profylaxis excepted)
f. Current intracranial bleeding
g. Traumatic brain or spinal injury within the last month
6. Patients requiring any form of antithrombotics (beyond profylaxis) in therapeutic doses or
prothrombotics in any dose, including:
a. Unfractionated heparin within 8 hours before the infusion (prophylactic heparin up to 15,000 U/day permitted)
b. LMWH within 12 hours before the infusion (prophylactic doses permitted)
c. Warfarin within 1 day before the infusion
d. Acetylsalicylic acid more than 650 mg/day within 3 days before the study
e. Thrombolytic therapy within 3 days before the study (catheter clearance doses permitted)
f. GPIIb/IIIa receptor inhibitors within 4 days before the study
g. Antithrombin III with dose greater than 10,000 U within 12 hours before the study
7. Patients with a do-not-resuscitate order (expected not to survive more than few days because of uncorrectable medical or surgical condition other than sepsis)
8. Patient with chronic renal failure requiring dialysis (renal failure without need for dialysis permitted)
9. Patients who have undergone transplantation of bone marrow, liver, pancreas, heart, lung, or bowel (kidney transplant permitted)
10. Patient with known hypercoagulable condition:
a. Activated protein C resistance
b. Hereditary protein C, protein S, or antithrombin III deficiency
c. Anticardiolipin or antiphospholipid antibody
d. Lupus anticoagulant
e. Homocysteinemia
f. Recent or highly suspected pulmonary embolism or deep venous thrombosis (within 3 months)
11. Patients with known congenital hypocoagulable diseases
12. Patient with known primary pulmonary hypertension

E.5 End points

E.5.1

Primary end point(s)

* Change in biomarkers indicative of endothelial activation and damage from baseline to 48 hours post-randomization
* Change in platelet count from baseline to 48 hours post-randomization
* Change in D-dimer and fibrin split products indicative of fibrinolysis from baseline to 48 hours post-randomization

E.5.1.1

Timepoint(s) of evaluation of this end point

48 hours post-randomization

E.5.2

Secondary end point(s)

* Severe bleeding (intracranial or clinical bleeding with the use of 3 RBC units or more/24 hours)
* Use of blood products (in ICU) post-randomization
* Difference in day 7, 30 and 90 day mortality between patients receiving active treatment and placebo
* Changes in SOFA score from baseline to 48 h and day 5 and 7 post-randomization
* Days of vasopressor, ventilator and renal replacement therapy post-randomization

E.5.2.1

Timepoint(s) of evaluation of this end point

The secondary endpoint are evaluated througout the 48 hour treatment period and after 7, 30 and 90 days

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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

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

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

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

All patients who withdraw from the trial for any reason and at any time
should have an end of trial examination. Patients will be examined for
any status changes that require further follow-up. All withdrawn
patients will be followed-up as the remaining patients in the trial. If
consent is withdrawn, the person making the withdrawal will be asked
for permission to follow up for 90 days after randomisation.

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

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

Yes

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Patients are at the investigator site in a critical acute condition resulting in mental impairment or sedation, therefore scientific guardians will co-sign the informed consent form. Next-of-kin and the patients' general practitioner will co-sign.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

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)

None

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

2014-07-30

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-08-14

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-11

Select Country:	Select Age Range:
Select Trial Status:	Select Trial Phase:
Select Gender:
Select Date Range: to
Select Rare Disease:
IMP with orphan designation in the indication
Orphan Designation Number:
Results Status:
Clear advanced search filters

Austria
Belgium
Bulgaria
Croatia
Cyprus
Czechia
Denmark
Estonia
Finland
France
Germany
Greece
Hungary
Iceland
Ireland
Italy
Latvia
Liechtenstein
Lithuania
Luxembourg
Malta
Netherlands
Norway
Poland
Portugal
Romania
Slovakia
Slovenia
Spain
Sweden
United Kingdom
Outside EU/EEA

Clinical trials