Safety Study of Calcineurin-Inhibitor-Free Immunosuppression After Liver Transplantation (CILT)

A Therapeutic Exploratory Study to Determine the Efficacy and Safety of Calcineurin-Inhibitor-Free De-novo Immunosuppression After Liver Transplantation

A prospective, non-randomized two stage monocentric phase II clinical trial to evaluate a de-novo calcineurin-inhibitor (CNI)-free immunosuppressive regimen based on induction therapy with anti-CD25 monoclonal anti-body (basiliximab), mycophenolic acid (MPA), and mammalian target of rapamycin (mTOR) - inhibition with everolimus to determine its safety and to investigate the preliminary efficacy in patients with impaired renal function at the time-point of liver transplantation (OLT) with regards to the incidence of steroid resistant acute rejection within the first 30 days after liver transplantation.

Study Overview

• Status: Unknown
• Conditions: Liver Transplantation; Chronic Renal Insufficiency
• Intervention / Treatment: Drug: Basiliximab (Simulect); Drug: Myfortic; Drug: everolimus; Drug: Prednisolone

• Study Type: Interventional
• Enrollment (Anticipated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Aiman Obed, Prof. Dr.; Phone Number: +49 551 3912296; Email: aobed@chirurgie-goettingen.de
• Study Contact Backup: Name: Armin D Goralczyk, MD; Phone Number: +49 551 3914638; Email: agoralczyk@med.uni-goettingen.de

Study Locations

• Germany
  • Goettingen, Germany, 37099
    • Recruiting
    • University Medical Center Goettingen
    • Contact: Armin D Goralczyk, Dr.; Phone Number: +49 551 398490; Email: agoralczyk@med.uni-goettingen.de
    • Contact: Aiman Obed, PD Dr.; Phone Number: +49 551 39 12296; Email: aobed@chirurgie-goettingen.de
    • Principal Investigator: Aiman Obed, Prof. Dr.
    • Sub-Investigator: Armin D Goralczyk, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients undergoing primary liver transplantation.
2. Patients older than 18 years.
3. Patients with a hepatorenal syndrome.
4. Female patients of childbearing potential willing to perform a highly effective contraception during the study and 12 weeks after conclusion of study participation.
5. eGFR < 50 ml/min at the time point of transplantation.
6. Serum creatinine levels > 1.5 mg/dL at the time-point of transplantation.

Exclusion Criteria:

1. Patients with pre-transplant renal replacement therapy > 14 days.
2. Patients with a reason for renal impairment other than a hepatorenal syndrome.
3. Patients with a known hypersensitivity to mTOR-inhibitors.
4. Patients with a known hypersensitivity to mycophenolate acid.
5. Patients with a known hypersensitivity to anti CD 25-monoclonal antibodies.
6. Patients with platelets < 50.000/nl prior to initiation of therapy with mTOR inhibition.
7. Patients with triglycerides > 350 mg/dl and cholesterol > 300 mg/dl refractory to optimal medical treatment prior to initiation of therapy with mTOR inhibition.
8. Severe systemic infections and wound-healing disturbances.
9. Multiple organ graft recipients.
10. Patients with signs of a hepatic artery stenosis directly prior to initiation of therapy with everolimus.
11. Pregnant women will not be included in the study.
12. Patients with a psychological, familial, sociologic or geographic condition potentially hampering compliance with the study protocol and follow-up schedule.
13. Patients under guardianship (e.g., individuals who are not able to freely give their informed consent).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: CNI-free Immunosuppression; Immunosuppression after OLT including basiliximab, enteric-coated mycophenolate sodium (EC-MPS), and everolimus.

Drug: Basiliximab (Simulect); 20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT; Other Names: Basiliximab: Simulect; Drug: Myfortic; 1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT; Other Names: Enteric-coated mycophenolate sodium: EC-MPS, Myfortic; Drug: everolimus; 1 mg q12 everolimus (Certican) po starting on 10th post-operative day; Other Names: Certican; Drug: Prednisolone; Prednisolone 1mg per kg body weight starting within 24 hours after transplantation. Then q24 but with reduction by 5 mg every 48 hours until maintenance dose of 7.5 mg; Other Names: Prednisone

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Steroid resistant rejection	30 days

Secondary Outcome Measures

Outcome Measure	Time Frame
Patient survival	1 year
Graft survival	1 year
Steroid resistant rejection	1 year
Liver function	1 year
Calculated glomerular filtration rate	1 year
Number of days on renal replacement therapy	1 year

Collaborators and Investigators

• Sponsor: Armin Goralczyk
• Investigators: Study Director: Aiman Obed, PD Dr., University Medical Center Goettingen; Principal Investigator: Armin D Goralczyk, Dr., University Medical Center Goettingen

Publications and helpful links

General Publications

• Goralczyk AD, Schnitzbauer A, Tsui TY, Ramadori G, Lorf T, Obed A. A therapeutic exploratory study to determine the efficacy and safety of calcineurin-inhibitor-free de-novo immunosuppression after liver transplantation: CILT. BMC Surg. 2010 Apr 9;10:15. doi: 10.1186/1471-2482-10-15.

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): January 1, 2012
• Study Completion (Anticipated): January 1, 2013

Study Registration Dates

• First Submitted: April 28, 2009
• First Submitted That Met QC Criteria: April 28, 2009
• First Posted (Estimate): April 29, 2009

Study Record Updates

• Last Update Posted (Estimate): September 15, 2011
• Last Update Submitted That Met QC Criteria: September 14, 2011
• Last Verified: January 1, 2010

More Information

Terms related to this study

• Keywords: Liver transplantation; Renal impairment; Chronic Renal Insufficiency
• Additional Relevant MeSH Terms: Kidney Diseases; Urologic Diseases; Renal Insufficiency, Chronic; Renal Insufficiency; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Anti-Inflammatory Agents; Antineoplastic Agents; Immunosuppressive Agents; Immunologic Factors; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Antitubercular Agents; Antibiotics, Antitubercular; Prednisolone; Prednisone; Mycophenolic Acid; Everolimus; Basiliximab
• Other Study ID Numbers: CILT08