Clinical trial NCT00905515: Optima: Optimizing Prograf Therapy in Maintenance Allografts II
Official title: Optima: Optimizing Prograf Therapy in Maintenance Allografts II
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Kidney Transplantation
Keywords: Kidney Transplantation
Immunosuppressive Agents
Lead sponsor: East Carolina University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2009-05-20
Enrollment: 63
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Renal Function in Patients Converted From Cyclosporine to Prograf
timeFrame: 3 years
measure: Optimal Dose of Calcineurin Inhibitor in Long-term Maintenance Kidney Transplant Patients
timeFrame: 3 years
measure: Change in Risk Factors for Cardiovascular Morbidity and Chronic Graft Dysfunction as Evidenced by Blood Levels of Homocysteine
timeFrame: 3 years
Secondary outcomes:
Other outcomes:
Locations:
city: Greenville
country: United States
facility: Brody School of Medicine at East Carolina University
state: North Carolina
Study officials:
affiliation: East Carolina University
name: Paul Bolin, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.