Optima: Optimizing Prograf Therapy in Maintenance Allografts II

NCT ID: NCT00905515

Last Updated: 2023-09-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 63 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-08-31
• Study Completion Date: 2008-07-31

Brief Summary

This study is designed to optimize calcineurin immunosuppressive regimens and evaluate immunological and non-immunological markers that may explain mechanistic differences in these agents and their effects.

Detailed Description

One of the major challenges in transplantation over the past two decades has been managing long-term renal function. Serum creatinine is the most commonly used serum marker of renal function. However serum creatinine is insensitive for detecting small decreases in glomerular filtration rate (GFR). Another marker for renal function is cystatin C. Dharnidharka et al concluded that cystatin C is superior to serum creatinine as a marker of kidney function since cystatin C was a more sensitive marker than serum creatinine for detecting decreases in GFR. Pirsch et al reported that tacrolimus-treated patients had a lower incidence of severe acute rejection and better lipid profiles than cyclosporine-treated patients.

Cardiovascular disease is the primary cause of premature death in renal and other transplant recipients. Current immunosuppressive protocols often elevate cardiovascular disease risk factors such as hypertension, hyperlipidemia, obesity and diabetes.

This study is designed to optimize calcineurin immunosuppressive regimens to ensure the best possible long-term outcomes after renal transplantation.

Conditions

Kidney Transplantation

Study Design

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

Study Groups

Control Group Cyclosporine

Maintain on Cyclosporine (CsA) at target trough level of 50-250 ng/mL.

Group Type: ACTIVE_COMPARATOR

cyclosporine

Intervention Type: DRUG

Maintain on cyclosporine at target trough level of 50-250 ng/mL.

Low Trough Level Prograf Group

Convert to Prograf (TAC) at target trough levels of 3.0-5.9 ng/mL.

Group Type: ACTIVE_COMPARATOR

Prograf (Tacrolimus)

Intervention Type: DRUG

Convert to Prograf at target trough levels of 3.0-5.9 ng/mL (Arm 2) or target trough levels of 6.0-8.9 ng/mL (Arm 3).

High Trough Level Prograf Group

Convert to TAC at target trough levels of 6.0-8.9 ng/mL.

Group Type: ACTIVE_COMPARATOR

Prograf (Tacrolimus)

Intervention Type: DRUG

Convert to Prograf at target trough levels of 3.0-5.9 ng/mL (Arm 2) or target trough levels of 6.0-8.9 ng/mL (Arm 3).

Interventions

cyclosporine

Maintain on cyclosporine at target trough level of 50-250 ng/mL.

Intervention Type: DRUG

Prograf (Tacrolimus)

Convert to Prograf at target trough levels of 3.0-5.9 ng/mL (Arm 2) or target trough levels of 6.0-8.9 ng/mL (Arm 3).

Intervention Type: DRUG

Other Intervention Names

Cyclosporine/Neoral®/Sandimmune®/Gengraf®; Tacrolimus/Prograf®/FK506

Eligibility Criteria

Inclusion Criteria

• Patient is the recipient of a cadervic or living donor renal transplant.
• Patient was 18 years of age at time of transplant.
• Patient is at least 6 months post-transplant.
• Patient has been on a cyclosporine-based immunosuppressive regimen since the transplant.
• Patient has a functioning allograft and a Cockcroft/Gault estimate of creatinine clearance >or= 35 mL/min within four weeks prior to randomization.
• Patient or legal guardian has signed and dated an Institutional Review Board (IRB) approved informed consent document and is willing and able to follow study procedures.
• Females are not pregnant and agree to practice effective birth control while receiving immunosuppressant medication.

Exclusion Criteria

• Patient is the recipient of a solid organ transplant other than the kidney.
• Patient experienced biopsy-confirmed, acute rejection, (Banff 97 criteria)within 3 months before randomization that required treatment, which is defined as antilymphocyte therapy, corticosteroids, or an increase in the number or dose of immunosuppressant medication.
• Patient has recurrence of primary renal disease, or de novo renal disease.
• Patient has a urine protein of > 1.5g/24 hours or two successive urinalyses sent to and reported by the laboratory indicating albuminuria greater than 2+ within 6 months prior to enrollment.
• Patient has an estimated creatinine clearance < 35 mL/min calculated using Cockcroft/Gault formula within four weeks prior to randomization.
• Patient has changed adjunctive immunosuppressant therapy within one month if randomization.
• Patient is pregnant or lactating.
• Patient is a known carrier of any of the HIV viruses.
• Patient has a known or suspected malignancy (except for treated squamous or basal cell skin cancers) < 5 years before randomization or a history of post-transplant lymphoproliferative disease (PTLD).
• Patient has a known hypersensitivity to tacrolimus, or any of the excipients of the drug.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Astellas Pharma US, Inc.

INDUSTRY

Sponsor Role: collaborator

East Carolina University

OTHER

Sponsor Role: lead

Responsible Party

Paul Bolin

Chair of Internal Medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Paul Bolin, MD

Role: PRINCIPAL_INVESTIGATOR

East Carolina University

Locations

Brody School of Medicine at East Carolina University

Greenville, North Carolina, United States

Countries

United States

References

Dharnidharka VR, Kwon C, Stevens G. Serum cystatin C is superior to serum creatinine as a marker of kidney function: a meta-analysis. Am J Kidney Dis. 2002 Aug;40(2):221-6. doi: 10.1053/ajkd.2002.34487.

Reference Type: BACKGROUND

PMID: 12148093 (View on PubMed)

Pirsch JD, Miller J, Deierhoi MH, Vincenti F, Filo RS. A comparison of tacrolimus (FK506) and cyclosporine for immunosuppression after cadaveric renal transplantation. FK506 Kidney Transplant Study Group. Transplantation. 1997 Apr 15;63(7):977-83. doi: 10.1097/00007890-199704150-00013.

Reference Type: BACKGROUND

PMID: 9112351 (View on PubMed)

Other Identifiers

MR-06-001

Identifier Type: -

Identifier Source: org_study_id