Sirolimus Conversions in African-American Renal Transplant Recipients

Absence; Kidney Clinical Trial

Official title:

A Pilot Study Comparing Two Different Sirolimus-based Transition Regimens in African-American Renal Transplant Recipients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01005706
• Other study ID #: Wyeth Study - HR 19042
• Secondary ID: HR19042
• Status: Completed
• Phase: N/A
• First received: October 9, 2009
• Last updated: February 12, 2016
• Start date: August 2009
• Est. completion date: July 2014

Study information

• Verified date: February 2014
• Source: Medical University of South Carolina
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 40
• Est. completion date: July 2014
• Est. primary completion date: July 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Absence; Kidney

Intervention

Drug:
• rapamune, mycophenolate mofetil and steroid
At the time of transition patients randomized into this arm of the study will receive loading doses of sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml. Patients randomized into this arm of the study will continue their current dosing regimen and frequency of mycophenolate mofetil. Serum trough level monitoring of mycophenolic acid will not be performed unless clinically warranted per standard of care and dosage adjustments from such levels will be made only with consent of the study primary investigator.
• tacrolimus, sirolimus and steroid
Tacrolimus dosing is based on 12-hour whole blood trough concentrations. Target blood concentration is 2-5 ng/ml. At the time of transition patients randomized into this arm of the study will receive loading doses of Sirolimus for two days and then 5mg PO daily. Twenty-four hour troughs will be checked per the schedule to ensure and monitor the therapeutic concentrations of 8-12ng/ml.

Locations

Country	Name	City	State
United States	The Medical University of South Carolina	Charleston	South Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Medical University of South Carolina	Wyeth is now a wholly owned subsidiary of Pfizer

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View Citation

Groth CG, Bäckman L, Morales JM, Calne R, Kreis H, Lang P, Touraine JL, Claesson K, Campistol JM, Durand D, Wramner L, Brattström 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. — View Citation

Ingle GR, Sievers TM, Holt CD. Sirolimus: continuing the evolution of transplant immunosuppression. Ann Pharmacother. 2000 Sep;34(9):1044-55. Review. — View Citation

Kahan BD, Camardo JS. Rapamycin: clinical results and future opportunities. Transplantation. 2001 Oct 15;72(7):1181-93. Review. — View 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. Review. — View Citation

MacDonald A. Improving tolerability of immunosuppressive regimens. Transplantation. 2001 Dec 27;72(12 Suppl):S105-12. Review. — View 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):1059-71. — View 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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Effectiveness and Safety of a Particular Drug Regimen to Prevent Kidney Rejection	Number of Participants with Kidney Rejections	12 months	Yes