Liver Graft DysfunctionIMUTECTNCT01781195
Delayed CNI-based Immunosuppression With Advagraf After MELD-based Liver Transplantation
An observational study of Liver Graft Dysfunction, run by Heidelberg University at 1 site in Germany.
Trial summary
Prolonged-release low-dose Advagraf should better protect from CNI-side effects compared to standard immunosuppressive regiments while the rate of rejection is not increased and thus graft function is well maintained. Read more about this study
- Who is it for?
- Ages 18 to 64 years
- Conditions the study is for
- Liver Graft Dysfunction
- How many people
- 50 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2013to Dec 2015
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 64 years
- All sexes
- No healthy volunteers
- Adult
Study population: patients with different MELD-scores/Na-MELD-scores undergoing liver transplantation
Who may be able to join
- age >18, <65
- first liver transplantation
- Immunosuppression with Advagraf, MMF, corticosteroid
- surgery and postoperative treatment at the department for general-, visceral- and transplantation surgery
Who cannot join
- missing informed consent
- re-transplantation
- acute infection: CMV (pp65 positive), pneumonia, urinary tract infection, wound infection, reactivation of Hepatitis B/C
Trial locations and contacts
1 site in 1 country.
Germany1 site, 1 recruiting
- Recruiting
University Surgical Clinic
Heidelberg, 69120
Peter Schemmer, Prof., +4962215636500, Peter.schemmer@med.uni-Heidelberg.de
Daniela Hall, +4962215636805, Daniela.hall@med.uni-Heidelberg.de
About this study
Official title: Effect of Delayed CNI-based Immunosuppression With Advagraf on Liver Function After MELD-based Liver Transplantation
Prolonged-release low-dose Advagraf should better protect from CNI-side effects compared to standard immunosuppressive regiments while the rate of rejection is not increased and thus graft function is well maintained. We hypothesize that especially in high-MELD (MELD-score >20) recipients who have a decreased immune competence the prolonged-release low-dose Advagraf concept would better protect from side effects of immunosuppression (i.e. infection). Nevertheless, we assume that also patients with a MELD-score ≤20 will benefit from this concept in regard to lower infection rates and less side effects of immunosuppression.
Read the detailed description
The MELD-score (model of end stage liver disease) was designed to estimate the prognosis after TIPS (transjugular intrahepatic porto-systemic shunt). Nowadays it is the key-score for patients awaiting a liver graft and consists of serum-creatinine, serum-bilirubine and the INR-ratio with values between 6-40. The MELD-based liver allocation follows the sickest patient first strategy which significantly decreased outcome after liver transplantation (LTx) in Germany. There is evidence that the immune competence of very sick patients is decreased. Monocytic HLA-DR status is a marker for the function of the immune system. A reduced monocytic HLA-DR expression is indicative for a suppressed immune system.
Blood levels of Advagraf are slowly increased during the first week until the aimed tacrolimus trough levels are reached. Since therapeutic tacrolimus trough levels are reached not before the end of the first week after transplantation this is a concept for prolonged-release immunosuppression.
We assume, that high-MELD patients (MELD >20) undergoing LTx are immunosuppressed per se. Thus prolonged-release low-dose immunosuppression with Advagraf would decrease both- infection rate (CMV-reactivation, wound infection urinary tract infections, pneumonia, etc.) and side effects of immunosuppression. The immune capacity of patients will be determined by the measurement of monocytic HLA-DR status. To ensure that graft function is not impaired due to rejection episodes, liver function will be determined with the LiMAx-test, a routine procedure in our institution. After 13-C-Methacetin is given to the patient, it is metabolized to paracetamol and 13CO2 by the enzyme CYP1A2 which is localized in hepatocytes. The 13CO2/12CO2 ratio in the exhaled air correlates with liver function.
- Conditions
- Liver Graft Dysfunction
- Keywords
- Advagraf, MELD-score, Na-MELD-score, liver function, LiMAx-test, infection rate, HLA-DR status, immunostatus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Advagraf-based immunosuppression | 50 patients after liver transplantation (25 with a MELD-score ≤20 and 25 patients with a MELD-score >20) under CNI-based immunosuppression with Advagraf |
What is being measured
The primary outcome is the main question the study is designed to answer.
infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)
clinical visit: infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)
Measured: 1-year follow-up per patient
Secondary outcomes (2)
liver function (LiMAx)
LiMAx test before liver transplantation, and on postoperative days 1, 3, 7
Measured: one week
HLA-DR status
HLA-DR status will be measured before liver transplantation and on postoperative days 3, 5, 7.
Measured: one week
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2013 (estimated)
- Study startFeb 2013
- Primary completionAug 2015 (estimated)
- Study completionDec 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Liver Graft DysfunctionStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Heidelberg University
- Sponsor type
- University, hospital or other
- Collaborators
- Astellas Pharma Inc
- Responsible party
- Principal investigator, Peter Schemmer, Heidelberg University
- Investigators
- Peter Schemmer, Prof., Principal investigator, University Hospital Heidelberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01781195
- Sponsor's protocol ID
- IMUTECT2013-01
- Acronym
- IMUTECT
- Status last verified
- May 2015
- First submitted
- 29 Jan 2013
- Last updated
- 28 May 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Richter S, Polychronidis G, Gotthardt DN, Houben P, Giese T, Sander A, Dorr-Harim C, Diener MK, Schemmer P. Effect of delayed CNI-based immunosuppression with Advagraf(R) on liver function after MELD-based liver transplantation [IMUTECT]. BMC Surg. 2014 Sep 1;14:64. doi: 10.1186/1471-2482-14-64.
PubMed 25178675
Study at a glance
From the registry record, last updated by the sponsor on 28 May 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Delayed CNI-based Immunosuppression With Advagraf on Liver Function After MELD-based Liver Transplantation
- ClinicalTrials.gov ID
- NCT01781195
- Acronym / sponsor ID
- IMUTECT / IMUTECT2013-01
- Conditions
- Liver Graft Dysfunction
- Keywords
- Advagraf, MELD-score, Na-MELD-score, liver function, LiMAx-test, infection rate, HLA-DR status, immunostatus
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Heidelberg UniversityUniversity, hospital or other
- Collaborators
- Astellas Pharma Inc
- Study start
- Feb 2013
- Primary completion
- Aug 2015 (estimated)
- Study completion
- Dec 2015 (estimated)
- First posted
- 31 Jan 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Prolonged-release low-dose Advagraf should better protect from CNI-side effects compared to standard immunosuppressive regiments while the rate of rejection is not increased and thus graft function is well maintained. We hypothesize that especially in high-MELD (MELD-score >20) recipients who have a decreased immune competence the prolonged-release low-dose Advagraf concept would better protect from side effects of immunosuppression (i.e. infection). Nevertheless, we assume that also patients with a MELD-score ≤20 will benefit from this concept in regard to lower infection rates and less side effects of immunosuppression.
Detailed description
The MELD-score (model of end stage liver disease) was designed to estimate the prognosis after TIPS (transjugular intrahepatic porto-systemic shunt). Nowadays it is the key-score for patients awaiting a liver graft and consists of serum-creatinine, serum-bilirubine and the INR-ratio with values between 6-40. The MELD-based liver allocation follows the sickest patient first strategy which significantly decreased outcome after liver transplantation (LTx) in Germany. There is evidence that the immune competence of very sick patients is decreased. Monocytic HLA-DR status is a marker for the function of the immune system. A reduced monocytic HLA-DR expression is indicative for a suppressed immune system.
Blood levels of Advagraf are slowly increased during the first week until the aimed tacrolimus trough levels are reached. Since therapeutic tacrolimus trough levels are reached not before the end of the first week after transplantation this is a concept for prolonged-release immunosuppression.
We assume, that high-MELD patients (MELD >20) undergoing LTx are immunosuppressed per se. Thus prolonged-release low-dose immunosuppression with Advagraf would decrease both- infection rate (CMV-reactivation, wound infection urinary tract infections, pneumonia, etc.) and side effects of immunosuppression. The immune capacity of patients will be determined by the measurement of monocytic HLA-DR status. To ensure that graft function is not impaired due to rejection episodes, liver function will be determined with the LiMAx-test, a routine procedure in our institution. After 13-C-Methacetin is given to the patient, it is metabolized to paracetamol and 13CO2 by the enzyme CYP1A2 which is localized in hepatocytes. The 13CO2/12CO2 ratio in the exhaled air correlates with liver function.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Advagraf-based immunosuppression | – | –50 patients after liver transplantation (25 with a MELD-score ≤20 and 25 patients with a MELD-score >20) under CNI-based immunosuppression with Advagraf |
Who may qualify
- Ages
- 18 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- patients with different MELD-scores/Na-MELD-scores undergoing liver transplantation
Key inclusion criteria (4 listed)
- age >18, <65
- first liver transplantation
- Immunosuppression with Advagraf, MMF, corticosteroid
- surgery and postoperative treatment at the department for general-, visceral- and transplantation surgery
Key exclusion criteria (3 listed)
- missing informed consent
- re-transplantation
- acute infection: CMV (pp65 positive), pneumonia, urinary tract infection, wound infection, reactivation of Hepatitis B/C
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)
Time frame: 1-year follow-up per patient
clinical visit: infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia)
2 secondary outcomes
liver function (LiMAx)
Time frame: one week
HLA-DR status
Time frame: one week
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 May 2015.
- Derived from this study: PubMed 25178675Richter S, Polychronidis G, Gotthardt DN, Houben P, Giese T, Sander A, Dorr-Harim C, Diener MK, Schemmer P. Effect of delayed CNI-based immunosuppression with Advagraf(R) on liver function after MELD-based liver transplantation [IMUTECT]. BMC Surg. 2014 Sep 1;14:64. doi: 10.1186/1471-2482-14-64.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Peter Schemmer, Prof. principal investigator
University Hospital Heidelberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Liver Graft Dysfunction, run by Heidelberg University at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 May 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Peter Schemmer, Prof. (+49-6221-566205, peter.schemmer@med.uni-heidelberg.de), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
infection rate (CMV reactivation, wound infection, urinary tract infection, pneumonia) (time frame: 1-year follow-up per patient). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01781195, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 May 2015.