Clinical trial NCT01005706: Sirolimus Conversions in African-American Renal Transplant Recipients
Official title: A Pilot Study Comparing Two Different Sirolimus-based Transition Regimens in African-American Renal Transplant Recipients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Absence; Kidney
Lead sponsor: Medical University of South Carolina
Sponsor class: OTHER
Collaborators: name: Wyeth is now a wholly owned subsidiary of Pfizer
First posted: 2009-11-01
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: This study's focus is to compare the level effectiveness and safety of regimens involving Sirolimus, Cellcept and steroid to Prograf, Sirolimus and steroid in African-American recipients of kidney transplants.

Detailed description: A major concern in transplantation is finding a successful regimen of medications to lower the potential for the body to reject the newly transplanted organ. The regimens in kidney transplantation include tacrolimus, sirolimus, mycophenolate mofetil and steroids. This study will compare the effectiveness and safety of a regimen including Sirolimus, Prograf, and steroids compared to a regimen including Sirolimus, Cellcept and steroids. These regimens have already been researched in the Caucasian population, and both drug regimens are FDA approved. This study's focus is on the effectiveness and safety of these regimens in African-Americans.

Eligibility criteria: Inclusion Criteria:

* At least 18 years of age and able to give informed consent
* African-American ethnicity
* Received a first or second non-ECD cadaveric or living donor renal transplant
* Transplant occurred during the past 6 to 24 weeks
* Patient has stable graft function, defined as no change of greater than 30% of baseline serum creatinine during the past month and no acute rejection in the past 6 weeks
* Estimated GFR using the modified MDRD equation of at least 40 mL/min10 at time of enrollment into the study
* Currently receiving tacrolimus, mycophenolate mofetil (at least 1 gm per day), and corticosteroids as their immunosuppression regimen.

Exclusion Criteria:

* Biopsy proven acute rejection episode that occurred within the past 6 weeks
* Malignancy within the past 3 years, except for non-melanoma skin cancer
* Any known intolerances to current immunosuppressant regimen necessitating withdrawal of the offending agent
* Currently enrolled in an investigational trial
* Woman of child bearing potential not utilizing an effective form of birth control
* Patients with uncontrolled dyslipidemia, defined at serum fasting LDL \>200 mg/dL or serum fasting triglycerides \>500 mg/dL.
* Patients with a spot urine protein to creatinine ratio of \> 800 mg of protein per gram of creatinine.
* WBC \< 3,000 cells/mm3
* Platelets \< 100,000 cells/mm3

Primary outcomes:
measure: Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection
timeFrame: 12 months
Secondary outcomes:
Other outcomes:
Locations:
city: Charleston
country: United States
facility: The Medical University of South Carolina
state: South Carolina
Study officials:
affiliation: Medical University of South Carolina
name: Charles Bratton, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Kahan BD, Camardo JS. Rapamycin: clinical results and future opportunities. Transplantation. 2001 Oct 15;72(7):1181-93. doi: 10.1097/00007890-200110150-00001. No abstract available.
citation: Sehgal SN. Rapamune (RAPA, rapamycin, sirolimus): mechanism of action immunosuppressive effect results from blockade of signal transduction and inhibition of cell cycle progression. Clin Biochem. 1998 Jul;31(5):335-40. doi: 10.1016/s0009-9120(98)00045-9.
citation: MacDonald A, Scarola J, Burke JT, Zimmerman JJ. Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Ther. 2000;22 Suppl B:B101-121. doi: 10.1016/s0149-2918(00)89027-x.
citation: Ingle GR, Sievers TM, Holt CD. Sirolimus: continuing the evolution of transplant immunosuppression. Ann Pharmacother. 2000 Sep;34(9):1044-55. doi: 10.1345/aph.19380.
citation: El-Sabrout R, Delaney V, Butt F, Qadir M, Hanson P, Tuteja S, McCollum DA, Butt K. Improved freedom from rejection after a loading dose of sirolimus. Transplantation. 2003 Jan 15;75(1):86-90. doi: 10.1097/00007890-200301150-00016.
citation: Podder H, Stepkowski SM, Napoli KL, Clark J, Verani RR, Chou TC, Kahan BD. Pharmacokinetic interactions augment toxicities of sirolimus/cyclosporine combinations. J Am Soc Nephrol. 2001 May;12(5):1059-1071. doi: 10.1681/ASN.V1251059.
citation: Groth CG, Backman L, Morales JM, Calne R, Kreis H, Lang P, Touraine JL, Claesson K, Campistol JM, Durand D, Wramner L, Brattstrom C, Charpentier B. Sirolimus (rapamycin)-based therapy in human renal transplantation: similar efficacy and different toxicity compared with cyclosporine. Sirolimus European Renal Transplant Study Group. Transplantation. 1999 Apr 15;67(7):1036-42. doi: 10.1097/00007890-199904150-00017.
citation: MacDonald A. Improving tolerability of immunosuppressive regimens. Transplantation. 2001 Dec 27;72(12 Suppl):S105-12.
citation: Fleming JN, Taber DJ, Pilch NA, McGillicuddy JW, Srinivas TR, Baliga PK, Chavin KD, Bratton CF. A randomized, prospective comparison of transition to sirolimus-based CNI-minimization or withdrawal in African American kidney transplant recipients. Clin Transplant. 2016 May;30(5):528-33. doi: 10.1111/ctr.12718. Epub 2016 Mar 14.