Impact of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2009 by Temple University.
Recruitment status was  Recruiting
Sponsor:
Collaborator:
Wyeth is now a wholly owned subsidiary of Pfizer
Information provided by:
Temple University
ClinicalTrials.gov Identifier:
NCT00999258
First received: October 20, 2009
Last updated: NA
Last verified: October 2009
History: No changes posted
  Purpose

The objective of this study is to examine the effect on allograft function and histology of converting African American renal transplant recipients with chronic allograft nephropathy (CAN) from a tacrolimus-based regimen to a sirolimus-based maintenance immunosuppression regimen.

The investigators hypothesize that the conversion from tacrolimus to sirolimus in African American renal recipients will stabilize or improve renal allograft function, and stabilize the histological progression of CAN. This conversion will have the potential to prolong long-term graft survival in African American renal transplant patients.

GFR measurements, histological parameters on the allograft biopsy, as well as patient and graft survival, incidence of acute rejection, and specific side effects will be monitored and compared between the sirolimus conversion group and the patients who will be maintained on tacrolimus.


Condition Intervention Phase
Glomerular Filtration Rate
Chronic Allograft Nephropathy
Drug: sirolimus
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Prospective Trial of Conversion From Tacrolimus to Sirolimus in African American Renal Transplant Recipients With Chronic Allograft Nephropathy

Resource links provided by NLM:


Further study details as provided by Temple University:

Primary Outcome Measures:
  • Glomerular filtration rate measured by Gd-DTPA [ Time Frame: 6 months, and 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Quantification the histological markers on renal allograft biopsy [ Time Frame: 1 year ] [ Designated as safety issue: No ]
  • Patient survival, graft survival, and incidence of acute rejection [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 50
Study Start Date: September 2009
Estimated Study Completion Date: June 2011
Estimated Primary Completion Date: June 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: sirolimus
the subjects will undergo conversion from tacrolimus to sirolimus OR they will continue to receive tacrolimus.
Drug: sirolimus

The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely.

The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care.

Other Name: GFR measurements and allograft biopsies
No Intervention: tacrolimus Drug: sirolimus

The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely.

The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care.

Other Name: GFR measurements and allograft biopsies

Detailed Description:

All African American renal transplant recipients (>3months and <5 years post-transplant) at our institution that are currently on a tacrolimus based regimen will be screened. Subjects with 10% or more decrease in glomerular filtration rate (GFR) from baseline, estimated by the MDRD formula,65 and who meet all inclusion criteria will be consented to be enrolled in the study. Baseline will be defined as the highest GFR estimated by MDRD formula, within 3 months of transplant.

Subjects who consent to participate in the study will undergo allograft biopsy and GFR measurement by Gd-DTPA, and will be randomly assigned (2:1) to undergo conversion from tacrolimus to sirolimus or to continue to receive tacrolimus.

The subjects assigned to the sirolimus conversion group will be initiated on sirolimus 5mg po daily at which time their tacrolimus dose will be decreased by 50%. Sirolimus levels will be checked within a week and adjusted in a linear fashion to achieve a trough goal of 12-15ng/ml in subjects within 1 year post-transplant, and 8-12 ng/ml in subjects more than 1 year post-transplant. Tacrolimus will be continued in these subjects until sirolimus target trough levels are achieved. Thereafter, tacrolimus will be discontinued indefinitely. Sirolimus trough levels will be monitored in the study as follows: weekly for the first month, monthly from 1 - 6 months, every 3 months from 6 months - 1 year post conversion. Subjects will continue to receive maintenance immunosuppression consisting of mycophenolate mofetil 500mg to 1000 mg po bid as tolerated and corticosteroid taper per protocol (maintenance of 2.5mg - 5mg po daily at 6 months post-transplant and then indefinitely). GFR measurement by DTPA will be repeated at 6 months, and 1 year post conversion. The second allograft biopsy will be performed at 1 year after sirolimus conversion.

The subjects assigned to the tacrolimus maintenance group (control group) represent our present standard of care. The subjects will continue to receive prednisone, and mycophenolate mofetil, similarly to the subjects assigned to the sirolimus conversion group. In the tacrolimus maintenance group, the subjects will be monitored according to our current clinic protocol, monthly between 3 months - 1 year post transplant, every two months in the second year post-transplant and every 3 months after 2 years. The tacrolimus dose will be adjusted to achieve a trough of 5-10ng/ml in subjects randomized to the control group which is standard of care per protocol. GFR measurement by DTPA will be repeated at 6 months, and 1 year post randomization. The second allograft biopsy will be performed at 1 year post randomization.

Patient and graft survival, and the incidence of acute rejection, proteinuria, hyperlipidemia, anemia, leucopenia, thrombocytopenia, and other clinical parameters will be monitored and compared between the sirolimus conversion group and the subjects who will be maintained on tacrolimus.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • African American (self-identified) renal transplant recipients.
  • Primary or re-transplant kidney-only recipients.
  • Recipients on tacrolimus-based immunosuppression regimen.
  • Time interval after transplant: at least 3 months but not greater than 5 years.
  • Renal transplant recipients with 10% decrease in GFR from baseline.
  • Women of childbearing potential must have a negative pregnancy test upon enrollment, and must consent to receive contraceptive counseling and to use effective contraception while enrolled in the study. Two reliable forms of contraception must be used simultaneously unless abstinence is the chosen method.

Exclusion Criteria:

  • GFR <40ml/min.
  • Urine protein-to-creatinine ratio >0.5.
  • Significant chronic allograft nephropathy grade 3 Banff score.
  • Evidence of acute rejection episodes within the past 3 months.
  • Evidence of active infection within the past month.
  • Any malignancy except treated non-melanoma skin cancer within the past 3 years.
  • Leucopenia <2,000/mm3 within the past month.
  • Thrombocytopenia <100,000/mm3 within the past month.
  • Total cholesterol >300mg/dl, despite adequate treatment.
  • Triglycerides >500mg/dl, despite adequate treatment.
  • Non-healed post-surgical or non-surgical wound.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00999258

Contacts
Contact: Serban Constantinescu, MD, PhD 215-707-9171 serban.constantinescu@tuhs.temple.edu
Contact: Sandra Amoroso, RN 215-707-7935 sandra.amoroso@tuhs.temple.edu

Locations
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Serban Constantinescu, MD, PhD    217-707-9171    serban.constantinescu@tuhs.temple.edu   
Principal Investigator: Serban Constantinescu, MD, PhD         
Sub-Investigator: Patricio Silva, MD         
Sub-Investigator: Nicole Sifontis, PharmD         
Sub-Investigator: Iris Lee, MD         
Sub-Investigator: John Daller, MD, PhD         
Sponsors and Collaborators
Temple University
Wyeth is now a wholly owned subsidiary of Pfizer
Investigators
Principal Investigator: Serban Constantinescu, MD, PhD Temple University
  More Information

No publications provided

Responsible Party: Serban Constantinescu, Temple University
ClinicalTrials.gov Identifier: NCT00999258     History of Changes
Other Study ID Numbers: 0468X1-4504
Study First Received: October 20, 2009
Last Updated: October 20, 2009
Health Authority: United States: Institutional Review Board

Keywords provided by Temple University:
glomerular filtration rate
chronic allograft nephropathy
Kidney transplantation
African American

Additional relevant MeSH terms:
Kidney Diseases
Urologic Diseases
Sirolimus
Everolimus
Tacrolimus
Antibiotics, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antifungal Agents
Anti-Infective Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Anti-Bacterial Agents

ClinicalTrials.gov processed this record on July 10, 2014