Clinical Trials Register

Summary
EudraCT Number:	2010-022660-12
Sponsor's Protocol Code Number:	PRAISE_ZKS0006
National Competent Authority:	Germany - BfArM
Clinical Trial Type:	EEA CTA
Trial Status:	Prematurely Ended
Date on which this record was first entered in the EudraCT database:	2010-11-22
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

Germany - BfArM

A.2

EudraCT number

2010-022660-12

A.3

Full title of the trial

A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of Iloprost in the early postoperative period after liver transplantation

A.3.1

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

A prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of Iloprost in the early postoperative period after liver transplantation

Prospektive, multizentrische, randomisierte, doppelblinde, placebo-kontrollierte Studie zur Evaluation von Iloprost in der frühen postoperativen Phase nach Lebertransplantation (PRAISE-Studie)

A.4.1

Sponsor's protocol code number

PRAISE_ZKS0006

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN12622749

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	Friedrich Schiller University
B.1.3.4	Country	Germany
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	BAYER Vital GmbH
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	Astellas Pharma GmbH
B.4.2	Country	Germany
B.4.1	Name of organisation providing support	SIRS-Lab GmbH
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	Friedrich Schiller University
B.5.2	Functional name of contact point	Dept. of Gen., Vis. and Vasc. Surg
B.5.3	Address:
B.5.3.1	Street Address	Erlanger Allee 101
B.5.3.2	Town/ city	Jena
B.5.3.3	Post code	07747
B.5.3.4	Country	Germany
B.5.4	Telephone number	+493641932 2688
B.5.5	Fax number	+493641932 2602
B.5.6	E-mail	erik.baerthel@med.uni-jena.de

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	Ilomedin
D.2.1.1.2	Name of the Marketing Authorisation holder	Bayer Vital GmbH, 51368 Leverkusen
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	Yes
D.2.5.1	Orphan drug designation number	EU/3/00/014
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
D.3.9.1	CAS number	78919-13-8
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	20
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	Concentrate for 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

the early postoperative period after liver transplantation

E.1.1.1

Medical condition in easily understood language

the early postoperative period after liver transplantation

frühe postoperative Periode nach Lebertransplantation

E.1.1.2

Therapeutic area

Body processes [G] - Physiological processes [G07]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	17.0
E.1.2	Level	LLT
E.1.2	Classification code	10024716
E.1.2	Term	Liver transplantation
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

Evaluation of Iloprost in the early postoperative period after liver transplantation

E.2.2

Secondary objectives of the trial

during trial duration: Occurrence of any infection up to day 28 after LT; Initial non-function defined as graft failure originating from the graft itself, excluding hepatic artery thrombosis, biliary complication, recurrent disease or acute rejection and resulting in retransplantation or patient death within 14 days after initial LT; Clotting factor substitution up to day 28 after LT; Renal replacement therapy up to day 28 and 180 after LT; Liver dialysis up to day 28 and 180 after LT; Graft survival at day 28 and 180 after LT; Patient survival at day 28 and 180 after LT; Occurrence of biliary complications at day 28 and 180 after LT; Length of ICU stay in days up to day 180 after LT; Length of hospital stay in days up to day 180 after LT; Course of ASAT/ALAT, Quick’s value/INR, Factor V and ICG-PDR until day 7 after LT; Change in SOFA-score from day 1 to day 7 after LT
Follow-up assessment 270 and 360 days after LT: Graft survival;Patient survival;Occurrence of biliary complications

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Full-size liver transplantation
2. Informed consent of the patient or legal representative
3. Age ≥ 18 years

E.4

Principal exclusion criteria

1.Women of child-bearing potential except women with the following criteria:
- post menopausal (12 month natural amenorrhoe or 6 month amenorrhoe with serum FSH > 40 mlU/ml)
- sterilization 86 weeks after bilateral ovarectomy with or without hysterectomy
- using an effective method of birth control for the duration of trial: implants, injectables, combined oral contraceptives, intra-uterine device (in place for a period of at least 2 months prior to screening) and with negative serum pregnancy test
- sexual abstinence
- vasectomised partner
2. Pregnancy/lactation
3. Respiratory and/or circulatory instability (noradrenaline > 1 µg/kgBW/min and FiO2 > 0.6) after LTx before randomization
4. Split liver transplantation / living donor related liver transplantation
5. Retransplantation
6. Multivisceral transplantation
7. Participation on other clinical trials 30 days prior to randomization
8. Known allergic reaction against trial medication
9. Conditions in which bleeding complications may be expected from the effect of Iloprost on platelets
10. Severe coronary artery disease or unstable angina pectoris
11. Myocardial infarction within the past 6 months prior to baseline assessment after acceptance of donor organ
12. Acute or chronic heart failure (NYHA II-IV)
13. Cardiac arrhythmias relevant for the prognosis
14. Suspected pulmonary artery congestion
15. known allergy or intolerance against tacrolimus, mycophenolate mofetil, basiliximab or corticosteroids

E.5 End points

E.5.1

Primary end point(s)

primary graft dysfunction (PDF) after liver transplantation characterized as
presentation of one or more of the following criteria: ALAT or ASAT level > 2000
IU/ml within the first 7 postoperative days, bilirubin ≥ 10 mg/dl on postoperative
day 7; INR ≥ 1.6 on postoperative day 7 or as occurrence of initial non-function
(INF) defined as graft failure originating from the graft itself, excluding hepatic artery thrombosis (HAT), biliary complication, recurrent disease or acute rejection and resulting in retransplantation or patient death within 14 days after initial LT

E.5.1.1

Timepoint(s) of evaluation of this end point

until day 14 after liver transplantation

E.5.2

Secondary end point(s)

during trial duration
- Occurrence of any infection up to day 28 after LT
- Initial non-function (INF) defined as graft failure originating from the graft itself, excluding hepatic artery thrombosis (HAT), biliary complication, recurrent disease or acute rejection and resulting in retransplantation or patient death within 14 days after initial LT
- Clotting factor substitution up to day 28 after LT
- Renal replacement therapy up to day 28 and 180 after LT
- Liver dialysis up to day 28 and 180 after LT
- Graft survival at day 28 and 180 after LT
- Patient survival at day 28 and 180 after LT
- Occurrence of biliary complications at day 28 and 180 after LT
- Length of ICU stay in days up to day 180 after LT
- Length of hospital stay in days up to day 180 after LT
- Course of ASAT/ALAT, Quick’s value/INR, Factor V and ICG-PDR until day 7 after LT
- Change in SOFA-score from day 1 to day 7 after LT

Follow-up assessment 270 and 360 days after LT:
- Graft survival
- Patient survival
- Occurrence of biliary complications

E.5.2.1

Timepoint(s) of evaluation of this end point

see above in E.5.2

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

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

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

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

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

end of trial: LVLS 180 d after LT
end of follow up: LVLS 360 d after LT

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:

370

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

Yes

F.3.3.6

Subjects incapable of giving consent personally

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

If patients are incapable of giving informed consent personally, than the legal representative is able to sign the informed consent. As soon as the patient is able to give his informed consent, he has to sign the consent form personally.

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

430

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)

is not different from the expected normal treatment of that condition

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

2010-12-17

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-02

P. End of Trial
P.	End of Trial Status	Prematurely Ended
P.	Date of the global end of the trial	2014-12-11

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