End Stage Liver DiseasePhase 3PATRON07NCT00604357
CNI-free de Novo Protocol in Patients Undergoing Liver Transplantation With Renal Impairment
A Phase 3 study testing anti-CD 25 mAb, Sirolimus, MMF in people with End Stage Liver Disease and Impaired Renal Function, run by University of Regensburg at 1 site in Germany.
Trial summary
Background: Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- End Stage Liver Disease, Impaired Renal Function
- What is being tested?
- anti-CD 25 mAb, Sirolimus, MMF
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 27 participants
- Where
- 1 siteGermany
- Study dates
- Dec 2008to Aug 2012
- Phase
- Phase 3
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients undergoing primary liver transplantation.
- Patients older than 18 years.
- Patients with a hepatorenal syndrome type I or II
- eGFR < 50 ml/min at the time point of transplantation
- Serum creatinine levels > 1.5 mg/dL at the time-point of transplantation
Who cannot join
- Patients with pre-transplant renal replacement therapy > 14 days.
- Patients with a known hypersensitivity to mTOR-inhibitors.
- Patients with a known hypersensitivity to mycophenolate acid.
- Patients with a known hypersensitivity to anti CD 25-monoclonal antibodies.
- Patients with platelets < 50.000/nl.
- Patients with triglycerides > 350 mg/dl and cholesterol > 300 mg/dl refractory to optimal medical treatment prior to initiation of therapy with mTOR inhibition.
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- Severe systemic infections and wound-healing disturbances prior to inclusion.
- Multiple organ graft recipients.
- Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with Sirolimus.
- Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.
- Patients under guardianship (e.g. individuals who are not able to freely give their informed consent).
Trial locations and contacts
1 site in 1 country.
Germany1 site
Regensburg University Medical Center, Department of Surgery
Regensburg, Bavaria, 93053
About this study
Official title: A Pilot Study to Determine the Safety and Efficacy of Induction-Therapy, De Novo MPA and Delayed mTOR-Inhibition in Liver Transplant Recipients With Impaired Renal Function. (PATRON-Study)
Background:
Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free regimens in patients with impaired renal function undergoing liver transplantation. The objective of the study is to evaluate a de novo calcineurin-inhibitor-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body, mycophenolate mofetil (MMF/MPA), and mTOR-inhibition to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time of liver transplantation. Methods/Design: Patients older than 18 years with renal impairment at the time of liver transplantation due to hepatorenal syndrome, eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients will receive a combination therapy with antiCD25-monoclonal antibodies, MMF, steroids and delayed sirolimus (day 10) and will be evaluated with regards to the incidence of steroid resistant acute rejection within the first 30 days after liver transplantation as the primary endpoint. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary end-point the regimen is regarded to be safe and efficient. The follow up period will be one year after transplantation. The aim is to obtain safety and efficacy data for this new and innovative therapy regimen that might be the basis for a large prospective randomized multicenter trial in the future.
Read the detailed description
Objectives of this study The objective of the study is to evaluate a de novo CNI-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body, mycophenolate mofetil (MMF/MPA), and delayed mTOR-inhibition. The primary endpoint is defined as the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation.
Secondary objectives include the incidence of acute rejection(s), the number and the timing of acute rejections per patient within the first year after transplantation. A critical secondary endpoint will be the development of renal function at 1 week, 1, 3, 6 and 12 months after liver transplantation. This includes information on the number of patients requiring renal replacement therapy and its duration. During follow-up of 1 year liver allograft function, infectious complications, treatment failures defined as introduction of CNIs as well as side-effects affecting the hematopoetic system, tolerability, impaired wound-healing, the incidence of hepatic artery thrombosis and mortality will be explicitly documented and investigated.
Trial population The collective we are aiming at are patients older than 18 years with a preexisting renal impairment at the time of liver transplantation. Patients will be eligible if the eGFR < 50 ml/min (Cockcroft-Gault) and/or their serum creatinine levels > 1.5 mg/dL.
Follow-Up Every patient will be followed up for 1 year after transplantation. The primary end-point will be at 30 days after transplantation (Steroid resistant acute rejection). During the first 30 days after transplantation there will be 9 visits where laboratory values (liver, renal and metabolic function, sirolimus trough levels), adverse events and rejection episodes will be recorded. Additionally there will be an ultrasound on day 1 after liver transplantation and on day 10 prior to the initiation of sirolimus to exclude hepatic artery thrombosis.
Between day 30 and 1 year after liver transplantation the patient will be followed up to evaluate the long time outcome and secondary objectives of the trial.
- Conditions
- End Stage Liver Disease, Impaired Renal Function
- Being tested
- anti-CD 25 mAb, Sirolimus, MMF
- Keywords
- CNI free, mTOR inhibition, induction, IL2 receptor antibodies, renal function, liver transplantation
- Medical subject headings
- End Stage Liver Disease, Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anti-CD 25 mAb, Sirolimus, MMFDrug
Also called Rapamune, Simulect, CellCept, DecortinH
Prior to reperfusion: 500 mg Prednisolone After OLT: anti-CD25-mAB (basiliximab 20 mg on day 0 and day 4 after the procedure)
MMF 2 g/d, 2 applications per day i.v., later conversion to oral intake)
Earliest, on day 10 after LT Sirolimus: 5 mg/d, thereafter a dosage of 2 mg/d (4 and 8 ng/mL)
Steroids: 1mg/kg BW (tapered every 2 days for 5 mg to a dosage of 20 mg, 2.5 mg every two days to 7.5 mg, reduced to 5 mg and 2.5 mg for 1 week each and eliminated thereafter).
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Prior to reperfusion 500 mg Prednisolone will be administered i.v.. After the transplantation, a combination of anti-CD25-mAB (basiliximab 20 mg on day 0 and day 4 after the procedure), and MMF 2 g/d, 2 applications per day i.v., later conversion to oral intake) will be applied. Earliest, on day 10 after LT Sirolimus will be introduced aiming at 24 hours trough-levels for Sirolimus between 4 and 8 ng/mL. Steroids will be started on day 1 after transplantation with 1mg/kg BW and will be tapered every 2 days for 5 mg to a dosage of 20 mg and for 2.5 mg every two days to 7.5 mg. Thereafter the dosage will be reduced to 5 mg and 2.5 mg for 1 week each and eliminated thereafter. Additionally, every patient with risk constellation will receive cytomegalovirus (CMV) prophylaxis and prophylaxis against Pneumocystis carinii infection during the first 3 months after liver transplantation. Receives: Drug: anti-CD 25 mAb, Sirolimus, MMF |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary endpoint is defined as the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation.
Measured: 30 days
Secondary outcomes (11)
incidence of acute rejection(s)
Measured: 1 year
the number and the timing of acute rejections
Measured: 1 year
the development of renal function at 1 week, 1, 3, 6 and 12 months after liver transplantation
Measured: 1 year
liver allograft function
Measured: 1 year
infectious complications
Measured: yes
treatment failures defined as introduction of CNIs
Measured: 1 year
side-effects affecting the hematopoetic system
Measured: 1 year
tolerability
Measured: 1 year
impaired wound-healing
Measured: 1 year
incidence of hepatic artery thrombosis
Measured: 1 year
mortality
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2008 (estimated)
- Study startDec 2008
- Primary completionJul 2011
- Study completionAug 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for End Stage Liver DiseaseStudies 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
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Regensburg
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hans J Schlitt, Prof. MD, University of Regensburg
- Investigators
- Andreas A Schnitzbauer, MD, Study director, Regensburg University Medical Center, Department of SurgeryHans J Schlitt, MD, Study chair, Regensburg University Medical Center, Department of SurgeryMarcus N Scherer, MD, Principal investigator, Regensburg University Medical Center, Department of Surgery
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00604357
- Sponsor's protocol ID
- PATRON07
- Acronym
- PATRON07
- Status last verified
- Dec 2014
- First submitted
- 17 Jan 2008
- Last updated
- 16 Dec 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Schnitzbauer AA, Sothmann J, Baier L, Bein T, Geissler EK, Scherer MN, Schlitt HJ. Calcineurin Inhibitor Free De Novo Immunosuppression in Liver Transplant Recipients With Pretransplant Renal Impairment: Results of a Pilot Study (PATRON07). Transplantation. 2015 Dec;99(12):2565-75. doi: 10.1097/TP.0000000000000779.
PubMed 26018348Schnitzbauer AA, Scherer MN, Rochon J, Sothmann J, Farkas SA, Loss M, Geissler EK, Obed A, Schlitt HJ. Study protocol: a pilot study to determine the safety and efficacy of induction-therapy, de novo MPA and delayed mTOR-inhibition in liver transplant recipients with impaired renal function. PATRON-study. BMC Nephrol. 2010 Sep 14;11:24. doi: 10.1186/1471-2369-11-24.
PubMed 20840760
Study at a glance
From the registry record, last updated by the sponsor on 16 Dec 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Determine the Safety and Efficacy of Induction-Therapy, De Novo MPA and Delayed mTOR-Inhibition in Liver Transplant Recipients With Impaired Renal Function. (PATRON-Study)
- ClinicalTrials.gov ID
- NCT00604357
- Acronym / sponsor ID
- PATRON07 / PATRON07
- Conditions
- End Stage Liver Disease, Impaired Renal Function
- Keywords
- CNI free, mTOR inhibition, induction, IL2 receptor antibodies, renal function, liver transplantation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of RegensburgUniversity, hospital or other
- Study start
- Dec 2008
- Primary completion
- Jul 2011 (actual)
- Study completion
- Aug 2012 (actual)
- First posted
- 30 Jan 2008 (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.
Background:
Patients undergoing liver transplantation with preexisting renal dysfunction are prone to further renal impairment with the early postoperative use of Calcineurin-inhibitors. However, there is only little scientific evidence for the safety and efficacy of de novo CNI free regimens in patients with impaired renal function undergoing liver transplantation. The objective of the study is to evaluate a de novo calcineurin-inhibitor-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body, mycophenolate mofetil (MMF/MPA), and mTOR-inhibition to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time of liver transplantation. Methods/Design: Patients older than 18 years with renal impairment at the time of liver transplantation due to hepatorenal syndrome, eGFR < 50 ml/min and/or serum creatinine levels > 1.5 mg/dL will be included. Patients will receive a combination therapy with antiCD25-monoclonal antibodies, MMF, steroids and delayed sirolimus (day 10) and will be evaluated with regards to the incidence of steroid resistant acute rejection within the first 30 days after liver transplantation as the primary endpoint. The study is designed as prospective two-step trial requiring a maximum of 29 patients. In the first step 9 patients will be included. If 8 or more patients show no signs of biopsy proven steroid resistant rejection, additional 20 patients will be included. If in the second step a total of 27 or more patients reach the primary end-point the regimen is regarded to be safe and efficient. The follow up period will be one year after transplantation. The aim is to obtain safety and efficacy data for this new and innovative therapy regimen that might be the basis for a large prospective randomized multicenter trial in the future.
Detailed description
Objectives of this study The objective of the study is to evaluate a de novo CNI-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti- body, mycophenolate mofetil (MMF/MPA), and delayed mTOR-inhibition. The primary endpoint is defined as the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation.
Secondary objectives include the incidence of acute rejection(s), the number and the timing of acute rejections per patient within the first year after transplantation. A critical secondary endpoint will be the development of renal function at 1 week, 1, 3, 6 and 12 months after liver transplantation. This includes information on the number of patients requiring renal replacement therapy and its duration. During follow-up of 1 year liver allograft function, infectious complications, treatment failures defined as introduction of CNIs as well as side-effects affecting the hematopoetic system, tolerability, impaired wound-healing, the incidence of hepatic artery thrombosis and mortality will be explicitly documented and investigated.
Trial population The collective we are aiming at are patients older than 18 years with a preexisting renal impairment at the time of liver transplantation. Patients will be eligible if the eGFR < 50 ml/min (Cockcroft-Gault) and/or their serum creatinine levels > 1.5 mg/dL.
Follow-Up Every patient will be followed up for 1 year after transplantation. The primary end-point will be at 30 days after transplantation (Steroid resistant acute rejection). During the first 30 days after transplantation there will be 9 visits where laboratory values (liver, renal and metabolic function, sirolimus trough levels), adverse events and rejection episodes will be recorded. Additionally there will be an ultrasound on day 1 after liver transplantation and on day 10 prior to the initiation of sirolimus to exclude hepatic artery thrombosis.
Between day 30 and 1 year after liver transplantation the patient will be followed up to evaluate the long time outcome and secondary objectives of the trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: anti-CD 25 mAb, Sirolimus, MMFPrior to reperfusion 500 mg Prednisolone will be administered i.v.. After the transplantation, a combination of anti-CD25-mAB (basiliximab 20 mg on day 0 and day 4 after the procedure), and MMF 2 g/d, 2 applications per day i.v., later conversion to oral intake) will be applied. Earliest, on day 10 after LT Sirolimus will be introduced aiming at 24 hours trough-levels for Sirolimus between 4 and 8 ng/mL. Steroids will be started on day 1 after transplantation with 1mg/kg BW and will be tapered every 2 days for 5 mg to a dosage of 20 mg and for 2.5 mg every two days to 7.5 mg. Thereafter the dosage will be reduced to 5 mg and 2.5 mg for 1 week each and eliminated thereafter. Additionally, every patient with risk constellation will receive cytomegalovirus (CMV) prophylaxis and prophylaxis against Pneumocystis carinii infection during the first 3 months after liver transplantation. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Patients undergoing primary liver transplantation.
- Patients older than 18 years.
- Patients with a hepatorenal syndrome type I or II
- eGFR < 50 ml/min at the time point of transplantation
- Serum creatinine levels > 1.5 mg/dL at the time-point of transplantation
Key exclusion criteria (11 listed)
- Patients with pre-transplant renal replacement therapy > 14 days.
- Patients with a known hypersensitivity to mTOR-inhibitors.
- Patients with a known hypersensitivity to mycophenolate acid.
- Patients with a known hypersensitivity to anti CD 25-monoclonal antibodies.
- Patients with platelets < 50.000/nl.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| anti-CD 25 mAb, Sirolimus, MMFAlso: Rapamune, Simulect, CellCept, DecortinHPrior to reperfusion: 500 mg Prednisolone After OLT: anti-CD25-mAB (basiliximab 20 mg on day 0 and day 4 after the procedure) MMF 2 g/d, 2 applications per day i.v., later conversion to oral intake) Earliest, on day 10 after LT Sirolimus: 5 mg/d, thereafter a dosage of 2 mg/d (4 and 8 ng/mL) Steroids: 1mg/kg BW (tapered every 2 days for 5 mg to a dosage of 20 mg, 2.5 mg every two days to 7.5 mg, reduced to 5 mg and 2.5 mg for 1 week each and eliminated thereafter). | Drug | 1 |
Primary outcome
The primary endpoint is defined as the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation.
Time frame: 30 days
11 secondary outcomes
incidence of acute rejection(s)
Time frame: 1 year
the number and the timing of acute rejections
Time frame: 1 year
the development of renal function at 1 week, 1, 3, 6 and 12 months after liver transplantation
Time frame: 1 year
liver allograft function
Time frame: 1 year
infectious complications
Time frame: yes
treatment failures defined as introduction of CNIs
Time frame: 1 year
side-effects affecting the hematopoetic system
Time frame: 1 year
tolerability
Time frame: 1 year
impaired wound-healing
Time frame: 1 year
incidence of hepatic artery thrombosis
Time frame: 1 year
mortality
Time frame: 1 year
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Dec 2014.
- Derived from this study: PubMed 26018348Schnitzbauer AA, Sothmann J, Baier L, Bein T, Geissler EK, Scherer MN, Schlitt HJ. Calcineurin Inhibitor Free De Novo Immunosuppression in Liver Transplant Recipients With Pretransplant Renal Impairment: Results of a Pilot Study (PATRON07). Transplantation. 2015 Dec;99(12):2565-75. doi: 10.1097/TP.0000000000000779.
- Derived from this study: PubMed 20840760Schnitzbauer AA, Scherer MN, Rochon J, Sothmann J, Farkas SA, Loss M, Geissler EK, Obed A, Schlitt HJ. Study protocol: a pilot study to determine the safety and efficacy of induction-therapy, de novo MPA and delayed mTOR-inhibition in liver transplant recipients with impaired renal function. PATRON-study. BMC Nephrol. 2010 Sep 14;11:24. doi: 10.1186/1471-2369-11-24.
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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.
Andreas A Schnitzbauer, MD study director
Regensburg University Medical Center, Department of Surgery
Hans J Schlitt, MD study chair
Regensburg University Medical Center, Department of Surgery
Marcus N Scherer, MD principal investigator
Regensburg University Medical Center, Department of Surgery
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing anti-CD 25 mAb, Sirolimus, MMF in people with End Stage Liver Disease and Impaired Renal Function, run by University of Regensburg 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 5 inclusion and 11 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: finished, as of the sponsor's last update on 16 Dec 2014. 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.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary endpoint is defined as the incidence of steroid-resistant acute rejection within the first 30 days after liver transplantation. (time frame: 30 days). 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 NCT00604357, which also lists 2 linked publications.
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 16 Dec 2014; AzTrials last refreshed its copy on 7 Nov 2026.