Safety Study of Calcineurin-Inhibitor-Free Immunosuppression After Liver Transplantation

Liver Transplantation Clinical Trial

— CILT  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00890253
• Other study ID #: CILT08
• Status: Recruiting
• Phase: Phase 2
• First received: April 28, 2009
• Last updated: September 14, 2011
• Start date: January 2010
• Est. completion date: January 2013

Study information

• Verified date: January 2010
• Source: University Medical Center Goettingen
• Contact: Aiman Obed, Prof. Dr.
• Phone: +49 551 3912296
• Email: aobed[@]chirurgie-goettingen.de
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 29
• Est. completion date: January 2013
• Est. primary completion date: January 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Renal Insufficiency
• Liver Transplantation
• Renal Insufficiency
• Renal Insufficiency, Chronic

Intervention

Drug:
• Basiliximab (Simulect)
20 mg basiliximab (Simulect) iv on day 0 and 4 after OLT
• Myfortic
1080 mg q12 EC-MPS (Myfortic) po starting within 24h after OLT
• everolimus
1 mg q12 everolimus (Certican) po starting on 10th post-operative day
• 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

Locations

Country	Name	City	State
Germany	University Medical Center Goettingen	Goettingen

Sponsors (1)

Lead Sponsor	Collaborator
Armin Goralczyk

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Steroid resistant rejection		30 days	Yes
Secondary	Steroid resistant rejection		1 year	Yes
Secondary	Liver function		1 year	Yes
Secondary	Calculated glomerular filtration rate		1 year	No
Secondary	Patient survival		1 year	Yes
Secondary	Number of days on renal replacement therapy		1 year	No
Secondary	Graft survival		1 year	Yes