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CNI-free "Bottom"-up Immunosuppression in Patients Undergoing Liver Transplantation (BUILT_01)

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ClinicalTrials.gov Identifier: NCT01023542
Recruitment Status : Unknown
Verified June 2011 by University of Regensburg.
Recruitment status was:  Recruiting
First Posted : December 2, 2009
Last Update Posted : July 1, 2011
Sponsor:
Collaborator:
Novartis Pharmaceuticals
Information provided by:
University of Regensburg

Brief Summary:
The primary objective of the trial is to evaluate efficacy and safety of delayed introduction (up to 30 days post-transplantation in patients without signs of acute rejection that had received an aIL-2 induction and MMF) of either cyclosporine or everolimus versus a 5-day delay of cyclosporine in combination with MMF.

Condition or disease Intervention/treatment Phase
Renal Impairment Liver Transplantation Everolimus Drug: delayed, low-dose CNI Drug: BU-CNI Drug: BU-Everolimus Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 45 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A 3-Armed Prospective Randomized Controlled, Open-Labeled Phase II Trial to Evaluate Late Introduction of Cyclosporine or Everolimus Versus a 5-day Delay of Cyclosporine in Combination With MMF in Liver Transplant Recipients With MELD-Scores≥25
Study Start Date : June 2011
Estimated Primary Completion Date : July 2014
Estimated Study Completion Date : December 2014

Resource links provided by the National Library of Medicine

Drug Information available for: Everolimus

Arm Intervention/treatment
Active Comparator: 1
Basiliximab 20 mg day 0 and 4 + MMF 2x1 g i.v./d from day 0 (will be switched to oral administration after 1 week) + low level cyclosporine [start at day 5 after OLT, trough-level 100-150 ng/mL (CsA)] + low-level steroids 1 mg/kg KG/d from day 0, elimination by month 6 after LTx.
Drug: delayed, low-dose CNI
immunosuppression

Active Comparator: 2
Basiliximab 20 mg Tag 0 and 4 + MMF 2x1 g i.v./d from day 0 (will be switched to oral administration after 1 week) + low-level steroids 1 mg/kg KG/d from day 0, elimination by month 6 after LTx + low-level cyclosporine (start within 30 days after LTx; trough level 100-150ng/mL (CsA).
Drug: BU-CNI
Immunosuppression

Experimental: 3
Basiliximab 20 mg Tag 0 and 4 + MMF 2x1 g i.v./d from day 0 (will be switched to oral administration after 1 week) + low-level steroids 1 mg/kg KG/d from day 0, elimination by month 6 after LTx + everolimus (start within 30 days after LTx; trough-level 6-10 ng/mL).
Drug: BU-Everolimus
Immunosuppression




Primary Outcome Measures :
  1. The primary outcome measure of the trial is renal function at 12 months measured by estimated GFR using abbreviated MDRD formula. [ Time Frame: 1 year ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male and female liver transplant recipients of a primary liver transplant older than 18 years
  2. Signed, written informed consent prior to randomization
  3. MELD scores ≥25
  4. Lack of relevant exclusion criteria

Exclusion Criteria:

  1. Patients transplanted for autoimmune hepatitis
  2. HIV positive patients
  3. Patients with pre-transplant immunosuppressive treatment
  4. Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant.
  5. Patients with renal failure or CKD/ESRD who require renal replacement therapy for more than 2 weeks prior to transplantation.
  6. Patients with signs of hepatic artery thrombosis.
  7. Patients with a hepatic encephalopathy grade of Stadium II, III and IV (somnolence, sopor and loss of consciousness
  8. Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
  9. Patients who are recipients of ABO incompatible transplant grafts.
  10. Patients with uncontrolled or therapy refractory hypercholesterolemia (>350 mg/dL; >9 mmol/L) or hypertriglyceridemia (>500 mg/dL; >8.5 mmol/L) at time of transplantation.
  11. Patients with platelet count <50,000/mm3 at the time of randomization.
  12. Patients with an absolute neutrophil count of <1,000/mm³ or white blood cell count of <2,000/mm³ at the time of randomization.
  13. Patients with a creatinine/protein ratio indicating daily urinary protein excretion > 1 g/24h at time of randomization.
  14. Women of child-bearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, including women whose career, lifestyle, or sexual orientation precludes intercourse with a male partner and women whose partners have been sterilized by vasectomy or other means, UNLESS (1) they meet the following definition of post-menopausal: 12 months of natural (spontaneous) amenorrhea or 6 months of spontaneous amenorrhea with serum FSH levels >40 mIU/m, or (2) have past 6 weeks from surgical bilateral oophorectomy with or without hysterectomy or (3) are using one or more of the following acceptable methods of contraception: surgical sterilization (e.g., bilateral tubal ligation, vasectomy), hormonal contraception (implantable, patch, oral), copper coated IUD and double-barrier methods ( any double combination of male or female condom with spermicidal gel, diaphragm, sponge, cervical cap). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception. Reliable contraception should be maintained throughout the and for 3 months after study drug discontinuation.
  15. Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation.
  16. Patients with a psychologic, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.
  17. Patients under guardianship (e.g. individuals who are not able to freely give their informed consent).

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To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01023542


Contacts
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Contact: Andreas A Schnitzbauer, MD +49-941944 ext 6770 andreas.schnitzbauer@klinik.uni-r.de
Contact: Susanne Melter, Study Nurse +49-941944 ext 6771 susanne.melter@klinik.uni-r.de

Locations
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Germany
Regensburg University Hospital Recruiting
Regensburg, Bavaria, Germany, 93053
Contact: Andreas A Schnitzbauer, MD    +49-941944 ext 6770    andreas.schnitzbauer@klinik.uni-r.de   
Sponsors and Collaborators
University of Regensburg
Novartis Pharmaceuticals
Investigators
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Principal Investigator: Andreas A Schnitzbauer, MD Regensburg University Hospital, Department of Surgery
Study Chair: Hans J Schlitt, MD Regensburg University Hospital Department of Surgery

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Responsible Party: Regensburg University, Regensburg University Hospital, Department of Surgery
ClinicalTrials.gov Identifier: NCT01023542     History of Changes
Other Study ID Numbers: BUILT_01
First Posted: December 2, 2009    Key Record Dates
Last Update Posted: July 1, 2011
Last Verified: June 2011

Keywords provided by University of Regensburg:
renal impairment
MELD>25
Liver transplantation
CNI-free
Bottom-Up
Everolimus

Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases
Everolimus
Sirolimus
Cyclosporins
Cyclosporine
Antineoplastic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Dermatologic Agents
Antirheumatic Agents
Calcineurin Inhibitors