Sirolimus Conversions in African-American Renal Transplant Recipients

NCT ID: NCT01005706

Last Updated: 2016-03-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 40 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-08-31
• Study Completion Date: 2014-07-31

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.

Conditions

Absence; Kidney

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Tacrolimus Withdrawal Arm

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.

Group Type: ACTIVE_COMPARATOR

rapamune, mycophenolate mofetil and steroid

Intervention Type: DRUG

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 Minimization Arm

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.

Group Type: ACTIVE_COMPARATOR

tacrolimus, sirolimus and steroid

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

rapamune (Sirolimus); mycophenolate mofetil (Cellcept); tacrolimus (Prograf); rapamune (Sirolimus)

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Wyeth is now a wholly owned subsidiary of Pfizer

INDUSTRY

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Charles Bratton, MD

Role: PRINCIPAL_INVESTIGATOR

Medical University of South Carolina

Locations

The Medical University of South Carolina

Charleston, South Carolina, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 11602840 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 9721431 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10823378 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10981252 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12544877 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 11316866 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10221490 (View on PubMed)

MacDonald A. Improving tolerability of immunosuppressive regimens. Transplantation. 2001 Dec 27;72(12 Suppl):S105-12.

Reference Type: BACKGROUND

PMID: 11833142 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 26914542 (View on PubMed)

Other Identifiers

HR19042

Identifier Type: -

Identifier Source: secondary_id

Wyeth Study - HR 19042

Identifier Type: -

Identifier Source: org_study_id