Condition category
Injury, Occupational Diseases, Poisoning
Date applied
14/08/2012
Date assigned
02/10/2012
Last edited
14/07/2016
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Background and study aims
The success of a liver transplantation depends on multiple factors. A poorly functioning liver graft increases the risk of complications, severe infections, and complete organ failure. For this reason, strategies are needed to reduce the number of poorly functioning liver grafts. One such possibility is the use of prostaglandin drugs, one of these being Iloprost. Prostaglandins widen the blood vessels and they prevent the aggregation of platelets, the blood cells responsible for clotting. This should improve the blood supply (perfusion) and functioning of the transplanted liver. The aim of this study is to examine whether the continuous use of Iloprost immediately after transplantation over seven days has a positive effect on the function of the transplanted liver.

Who can participate?
Patients aged over 18 receiving a liver transplant

What does the study involve?
Participants are randomly allocated to one of two groups. In the treatment group, participants receive Iloprost continuously intravenously (into a vein) over seven days; in the control group participants receive a placebo (dummy drug) intravenously with the same dosage.

What are the possible benefits and risks of participating?
Iloprost improves the perfusion of the transplanted liver, which may improve the functioning of the liver graft and may reduce the risk of complications. The most frequent drug-related side effects are flushing, headache, nausea and vomiting. Many of these side effects are dose-dependent and may be reduced or stopped by a dosage adjustment.

Where is the study run from?
Lead centre: Jena University Hospital. Further participating centres: Charite Campus Virchow, University Medicine Berlin; University Hospital of Essen; Goethe University Hospital Frankfurt, University Hospital of Mainz, University Hospital of Heidelberg (Germany)

When is the study starting and how long is it expected to run for?
April 2012 to December 2015

Who is funding the study?
1. Astellas GmbH
2. German Federal Ministry of Education and Research
3. BayerVital GmbH

Who is the main contact?
Dr Erik Bärthel

Trial website

http://www.praise.uniklinikum-jena.de

Contact information

Type

Scientific

Primary contact

Prof Utz Settmacher

ORCID ID

Contact details

University Hospital of Jena
Department of General Visceral and Vascular Surgery
Erlanger Allee 101
Jena
07740
Germany

Additional identifiers

EudraCT number

2010-022660-12

ClinicalTrials.gov number

Protocol/serial number

PRAISE-ZKS0006, DRKS00003514

Study information

Scientific title

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

Acronym

PRAISE

Study hypothesis

Improved graft viability under treatment with systemically administered prostacyclin analogue iloprost.

Ethics approval

Medical Faculty Ethics Committee, Friedrich Schiller University of Jena, 25/01/2011, ref: 2980-11/10

Study design

Prospective multi-center randomized double-blinded placebo-controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet (in German)

Condition

Liver transplantation

Intervention

Patients of the treatment group received 1 ng/kg body weight /min iloprost, intravenous administered for 7 days post-liver transplantation, in contrast to the control (placebo) population.

Intervention type

Drug

Phase

Not Applicable

Drug names

Iloprost

Primary outcome measures

Current primary outcome measures as of 07/03/2013:
Primary graft dysfunction (PDF) after liver transplantation characterized as presentation of one or more of the following criteria:
1. Alanine amino transferase / Aspartate amino transferase (ALAT or ASAT) level > 2000 lu/ml within the first 7 postoperative days
2. Bilirubin ≥ 10 mg/dl on postoperative day 7
3. INR ≥ 1.6 on postoperative day 7 or as occurrence of initial non-function (lNF) 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

Previous primary outcome measures:
Primary graft dysfunction (PDF) after liver transplantation characterized as presentation of one or more of the following criteria:
1. Alanine amino transferase / Aspartate amino transferase (ALAT or ASAT) level > 2000 lu/ml within the first 7 postoperative days
2. Bilirubin ≥ 10 mg/dl on postoperative day 7
3. INR ≥ 1.6 on postoperative day 7 or as occurrence of initial non-function (lNF) defined as graft failure originating from the graft itself, excluding hepatic artery thrombosis (HAT)
4. Biliary complication
5. Recurrent disease or acute rejection and resulting in retransplantation or patient death within 14 days after initial LT

Secondary outcome measures

Current secondary outcome measures as of 07/03/2013:
1. Occurence of any infection up to day 28 after LT
2. Initial non-function (lNF) 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
3. Clotting factor substitution up to day 28 after LT
4. Renal replacement therapy up to day 28 and 180 after LT
5. Liver dialysis up to day 28 and 180 after LT
6. Graft survival at day 28 and 't 80 after LT
7. Patient survival at day 28 and 180 after LT
8. Occurrence of biliary complications at day 28 and 180 after LT
9. Length of ICU stay in days up to day 180 after LT (max)
10. Length of hospital stay in days up to day 180 after LT (maximum)
11. Course of ASAT/ALAT, Quick's value/lNR, Factor V and Indocyanine green plasma disappearance rate (ICG-PDR) until day 7 after LT
12. Change in Sequential Organ Failure Assessment (SOFA)-score from day 1 to day 7 after LT

Previous secondary outcome measures:
1. Initial non-function (lNF) 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 2. Clotting factor substitution up to day 28 after LT
3. Renal replacement therapy up to day 28 and 180 after LT
4. Liver dialysis up to day 28 and 180 after LT
5. Graft survival at day 28 and 't 80 after LT
6. Patient survival at day 28 and 180 after LT
7. Occurrence of biliary complications at day 28 and 180 after LT
8. Length of hospital stay in days up to day 180 after LT (maximum)
9. Course of ASAT/ALAT, Quick's value/lNR, Factor V and Indocyanine green plasma disappearance rate (ICG-PDR) until day 7 after LT
10. Change in Sequential Organ Failure Assessment (SOFA)-score from day 1 to day 7 after LT

Overall trial start date

30/04/2012

Overall trial end date

31/12/2015

Reason abandoned

Eligibility

Participant inclusion criteria

Current inclusion criteria as of 07/03/2013:
1. Full-size liver transplantation
2. Informed consent of the patient or legal representative
3. Aged 18 years or over

Previous inclusion criteria:
1. Full-size liver transplantation
2. Informed consent of the patient or legal representative
3. Age over 18 years

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

356 randomised (900 screened, 430 with written consent)

Participant exclusion criteria

1. Women of child-bearing potential except women with the following criteria:
1.1. Post menopausal (12 months natural amenorrhea or 6 month amenorrhea with serum FSH > 40 mlU/ml)
1.2. Sterilization 86 weeks after bilateral ovarectomy with or without hysterectomy
1.3. Using an effective method of birth control for the duration of trial:
1.3.1 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
1.4. Sexual abstinence
2. Pregnancy/lactation
3. Respiratory and/or circulatory instability (noradrenaline > 1 pg/kgBWmin and FiOz > 0.6) after liver transplantation (LT) before randomization
4. Split liver transplantation/living donor related liver transplantation
5. Retransplantation
6. Receiving a multi-organ 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 lloprost 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 ll-lV)
13. Cardiac arrhythmias relevant for the prognosis
14. Suspected pulmonary artery congestion
15. Known allergy or intolerance against tacrolimus, mycophenolate mofetil, basiliximab or corticosteroids

Recruitment start date

30/04/2012

Recruitment end date

31/12/2015

Locations

Countries of recruitment

Germany

Trial participating centre

University Hospital of Jena
Jena
07740
Germany

Sponsor information

Organisation

Friedrich-Schiller-University Jena (Germany)

Sponsor details

Fürstengraben 1
Jena
07743
Germany

Sponsor type

University/education

Website

http://www.uni-jena.de/

Funders

Funder type

Hospital/treatment centre

Funder name

Universitätsklinikum Jena

Alternative name(s)

Jena University Hospital, UKJ

Funding Body Type

private sector organisation

Funding Body Subtype

academic

Location

Germany

Funder name

Bayer

Alternative name(s)

Funding Body Type

private sector organisation

Funding Body Subtype

corporate

Location

Germany

Funder name

Astellas Pharma GmbH (Germany)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

2013 protocol in: http://www.ncbi.nlm.nih.gov/pubmed/23356494

Publication citations

  1. Protocol

    Bärthel E, Rauchfuss F, Hoyer H, Breternitz M, Jandt K, Settmacher U, The PRAISE study: a prospective, multi-center, randomized, double blinded, placebo-controlled study for the evaluation of iloprost in the early postoperative period after liver transplantation (ISRCTN12622749)., BMC Surg, 2013, 13, 1, doi: 10.1186/1471-2482-13-1.

Additional files

Editorial Notes

14/07/2016: Plain English summary added. 07/03/2013: the overall trial start date was changed from 01/04/2012 to 30/04/2012.