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

NCT01023542 | Unknown Phase 2 DMC

• 1 other identifier: BUILT_01
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

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.

Conditions

Renal Impairment; Liver Transplantation; Everolimus

Keywords

renal impairment; MELD>25; Liver transplantation; CNI-free; Bottom-Up; Everolimus

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure of the trial is renal function at 12 months measured by estimated GFR using abbreviated MDRD formula.

  1 year

Study Arms (3)

1

ACTIVE COMPARATOR

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

2

ACTIVE COMPARATOR

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

3

EXPERIMENTAL

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

Interventions

delayed, low-dose CNI DRUG

immunosuppression

1

BU-CNI DRUG

Immunosuppression

2

BU-Everolimus DRUG

Immunosuppression

3

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male and female liver transplant recipients of a primary liver transplant older than 18 years
• Signed, written informed consent prior to randomization
• MELD scores ≥25

You may not qualify if:

• Patients transplanted for autoimmune hepatitis
• HIV positive patients
• Patients with pre-transplant immunosuppressive treatment
• Patients who are recipients of multiple solid organ or islet cell tissue transplants, or have previously received an organ or tissue transplant.
• Patients with renal failure or CKD/ESRD who require renal replacement therapy for more than 2 weeks prior to transplantation.
• Patients with signs of hepatic artery thrombosis.
• Patients with a hepatic encephalopathy grade of Stadium II, III and IV (somnolence, sopor and loss of consciousness
• Patients with a known hypersensitivity to the drugs used on study or their class, or to any of the excipients.
• Patients who are recipients of ABO incompatible transplant grafts.
• 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.
• Patients with platelet count \<50,000/mm3 at the time of randomization.
• Patients with an absolute neutrophil count of \<1,000/mm³ or white blood cell count of \<2,000/mm³ at the time of randomization.
• Patients with a creatinine/protein ratio indicating daily urinary protein excretion \> 1 g/24h at time of randomization.
• 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.
• Patients with any history of coagulopathy or medical condition requiring long-term anticoagulation which would preclude liver biopsy after transplantation.

Sponsors & Collaborators

• University of Regensburg: lead
• Novartis Pharmaceuticals: collaborator

Study Sites (1)

Regensburg University Hospital

Regensburg, Bavaria, 93053, Germany

RECRUITING

MeSH Terms

Conditions

Renal Insufficiency

Interventions

cni protein, Drosophila

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Andreas A Schnitzbauer, MD

  Regensburg University Hospital, Department of Surgery

  PRINCIPAL INVESTIGATOR

• Hans J Schlitt, MD

  Regensburg University Hospital Department of Surgery

  STUDY CHAIR

Central Study Contacts

Andreas A Schnitzbauer, MD

CONTACT

+49-941944; andreas.schnitzbauer@klinik.uni-r.de

Susanne Melter, Study Nurse

CONTACT

+49-941944; susanne.melter@klinik.uni-r.de

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 1, 2009
• First Posted: December 2, 2009
• Study Start: June 1, 2011
• Primary Completion: July 1, 2014
• Study Completion: December 1, 2014
• Last Updated: July 1, 2011

Record last verified: 2011-06

Locations

DE (1)