Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA (Enteric Coated Mycophenolic Acid) Following Liver Transplantation

Liver Transplantation Clinical Trial

Official title:

Safety and Efficacy of Basiliximab, Delayed Dose Tacrolimus Plus ECMPA, Versus Standard Dose Tacrolimus, ECMPA Plus Corticosteroids in Patients Undergoing Liver Transplant

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02123108
• Other study ID #: UCLA: CCHI621AUS17T
• Status: Completed
• Phase: Phase 4
• Start date: January 2011
• Est. completion date: January 2015

Study information

• Verified date: September 2022
• Source: University of California, Los Angeles
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an investigator initiated study at the University of California, Los Angeles (UCLA) funded by Novartis looking at using a combination of immunosuppressive drugs in liver transplant patients that are at risk of developing kidney problems. Kidney problems following liver transplants is the most problematic issue facing liver transplant patients today.

This study will generate information in this area of high unmet medical need utilizing basiliximab and Myfortic and using a reduced dose of tacrolimus, one of the current standard of care medications, after kidney function has normalized.

Description:

Since basiliximab works on the same receptor system as tacrolimus and has not been shown to cause significant adverse effects, such as nephrotoxicity or the cytokine release syndrome, the investigators are proposing induction therapy with basiliximab in liver transplant patients with concomitant preoperative renal dysfunction. This will combat acute rejection and allow the delay of tacrolimus therapy until post-operative day #7. The delay in tacrolimus therapy should allow renal function to improve and reduce the chance of continued renal dysfunction. Also, the addition of basiliximab to the immunosuppressive regimen should allow for a reduction in tacrolimus dose (normal tacrolimus concentrations at UCLA are 7-10ng/mL. Our goal will be 3-5ng/mL) in the immediate post-transplant period thereby reducing the chance of acute and long-term efficacy-limiting adverse effects associated with the tacrolimus while maintaining adequate immunosuppression to reduce acute rejection episodes. This would be the most convincing prospective randomized study utilizing basiliximab as a renal sparing agent in liver transplantation.

Objectives Primary objectives

• To evaluate renal recovery/ function following OLT in patients undergoing orthotopic liver transplant at 6 and 12 months post-transplant.

Secondary objectives (comparing the two treatment arms)

• To determine the tolerability and adverse event profile during the first year post-transplant.

• To determine incidence and severity acute rejection episodes

• To determine the incidence of death and/or graft failure within the first year post-transplant

Study design The study is a single center prospective randomized trial wherein the investigators will have two groups. Patients will be screened and eligible patients will be enrolled pre-transplant. Patients will then be randomized at time of transplant to either the control or treatment arm. Post transplant laboratory data (chemistry, tacrolimus level and liver function tests) will be collected on a daily basis. For the duration of the patients' hospital stay (average 2-3 weeks). This will provide the early data set for early post operative results. Patients will subsequently be followed on a weekly outpatient basis upon discharge as per protocol. During these visits, laboratory data (chemistry, tacrolimus level and liver function tests) are also collected and will provide the continued flow of data for our follow up analysis. Any evidence of rejection will prompt treatment with rescue therapy and if necessary disenrollment from the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 59
• Est. completion date: January 2015
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:

Patients eligible for inclusion in this study have to fulfill all of the following criteria:

• >18 years old

• Undergoing first or second OLT

• MELD (model for end-stage liver disease) score >25

• Serum creatinine > 1.5 or ongoing hemodialysis for less than 4 weeks at the time of transplant

• Able and agreeable to conform to requirements of the study

• Patients or proxy must give written informed consent before any assessment is performed.

Exclusion Criteria:

• <18 years old

• Serum creatinine <1.5

• MELD Score < 25

• Ongoing hemodialysis for 4 or more weeks (those patients become eligible for renal transplants at that point per UCLA practice).

• Receiving OKT3 (Muromonab-CD3), ATG (Antithymocyte Globulin), or IVIG (Intravenous Immunoglobulin Therapy) therapy around time of transplant

• Participating in another clinical research study involving the evaluation of another investigational drug or device

• Prior documented allergy to any of the study medications

• Active Fungal infection

Related Conditions & MeSH terms

• Liver Transplantation

Intervention

Drug:
• Basiliximab
Peri-operative 40 mg IV dose within 4 hours of OLT Postoperative 20mg IV dose Day 4
• Tacrolimus
Day #7 post-transplant or when serum creatinine (SCr) < 1.8 mg/dl 6 months to 1 year: 0.03-0.1 mg.kg q12h po to maintain whole blood trough concentration of 3-5ng/mL
• Tacrolimus
Day #1 post-transplant to 6 months: 0.03-0.1mg/kg q12h po to maintain whole blood trough concentration of 7-10 ng/mL + 6 months to 1 year: maintain whole blood trough concentration of 5-8ng/mL
• Mycophenolic Acid
Enteric coated mycophenolic acid 360-720 mg po bid

Locations

Country	Name	City	State
United States	Ronald Reagan UCLA Medical Center	Los Angeles	California

Sponsors (2)

Lead Sponsor	Collaborator
University of California, Los Angeles	Novartis

Country where clinical trial is conducted

United States, 

References & Publications (10)

Berard JL, Velez RL, Freeman RB, Tsunoda SM. A review of interleukin-2 receptor antagonists in solid organ transplantation. Pharmacotherapy. 1999 Oct;19(10):1127-37. Review. — View Citation

Calmus Y, Scheele JR, Gonzalez-Pinto I, Jaurrieta EJ, Klar E, Pageaux GP, Scudamore CH, Cuervas-Mons V, Metselaar HJ, Prestele H, Girault D. Immunoprophylaxis with basiliximab, a chimeric anti-interleukin-2 receptor monoclonal antibody, in combination with azathioprine-containing triple therapy in liver transplant recipients. Liver Transpl. 2002 Feb;8(2):123-31. — View Citation

Cherqui D, Duvoux C, Charlotte F, Humeres R, Lauzet JY, Métreau JM, Salvat A, Rotman N, Julien M, Fagniez PL, et al. [Value of a powerful initial immunosuppression after liver transplantation. Prospective study of 60 cases]. Gastroenterol Clin Biol. 1994;18(2):115-22. Review. French. — View Citation

Guckelberger O, Bechstein WO, Neuhaus R, Luesebrink R, Lemmens HP, Kratschmer B, Jonas S, Neuhaus PL. Cardiovascular risk factors in long-term follow-up after orthotopic liver transplantation. Clin Transplant. 1997 Feb;11(1):60-5. — View Citation

Katari SR, Magnone M, Shapiro R, Jordan M, Scantlebury V, Vivas C, Gritsch A, McCauley J, Starzl T, Demetris AJ, Randhawa PS. Clinical features of acute reversible tacrolimus (FK 506) nephrotoxicity in kidney transplant recipients. Clin Transplant. 1997 Jun;11(3):237-42. — View Citation

Klintmalm GB, Gonwa TA. Nephrotoxicity associated with cyclosporine and FK506. Liver Transpl Surg. 1995 Sep;1(5 Suppl 1):11-9. Review. — View Citation

Neuhaus P, Clavien PA, Kittur D, Salizzoni M, Rimola A, Abeywickrama K, Ortmann E, Chodoff L, Hall M, Korn A, Nashan B; CHIC 304 International Liver Study Group. Improved treatment response with basiliximab immunoprophylaxis after liver transplantation: results from a double-blind randomized placebo-controlled trial. Liver Transpl. 2002 Feb;8(2):132-42. — View Citation

Onrust SV, Wiseman LR. Basiliximab. Drugs. 1999 Feb;57(2):207-13; discussion 214. Review. — View Citation

Ramirez CB, Marino IR. The role of basiliximab induction therapy in organ transplantation. Expert Opin Biol Ther. 2007 Jan;7(1):137-48. Review. — View Citation

Rimola A, Gavaler JS, Schade RR, el-Lankany S, Starzl TE, Van Thiel DH. Effects of renal impairment on liver transplantation. Gastroenterology. 1987 Jul;93(1):148-56. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Participants Experiencing Adverse Event Attributable to Study Drug		12 months post liver transplantation
Other	Participants Experiencing Acute Rejection Episode		12 months post liver transplant
Other	Survival	Participants at risk minus incidence of death within the first year post-transplant	12 months post liver transplant
Other	Participants Experiencing Graft Failure		12 months post transplant
Primary	Renal Recovery/ Function	Number of participants who experienced dialysis independence or improvement based upon kidney function labs as a measure of renal recovery/ function following OLT in patients after undergoing orthotopic liver transplant	12 months post-transplant