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Optima: Optimizing Prograf Therapy in Maintenance Allografts II (OPTIMAII)

This study has been completed.
Sponsor:
Collaborator:
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Paul Bolin, East Carolina University
ClinicalTrials.gov Identifier:
NCT00905515
First received: May 18, 2009
Last updated: January 4, 2013
Last verified: January 2013
History of Changes
  Purpose

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.


Condition Intervention Phase
Kidney Transplantation
 Drug: cyclosporine
Drug: Prograf (Tacrolimus)
 Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Optima: Optimizing Prograf Therapy in Maintenance Allografts II

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by East Carolina University:

Primary Outcome Measures:
  • Renal Function in Patients Converted From Cyclosporine to Prograf [ Time Frame: 6 months, 1 year, 2 years and 3 years ] [ Designated as safety issue: Yes ]
  • Optimal Dose/Blood Level of Prograf in Long-term Maintenance Kidney Transplant Patients [ Time Frame: 6 months, 1 year, 2 years, 3 years ] [ Designated as safety issue: Yes ]
  • Change in Risk Factors for Cardiovascular Morbidity and Chronic Graft Dysfunction as Evidenced by Blood Levels of Homocysteine and Transforming Growth Factor Beta (TGF-B) [ Time Frame: 6 months, 1 year, 2 years, 3 years ] [ Designated as safety issue: Yes ]

Enrollment: 63
Study Start Date: August 2003
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Maintain on Cyclosporine (CsA) at target trough level of 50-250 ng/mL.
 Drug: cyclosporine
Maintain on cyclosporine at target trough level of 50-250 ng/mL.
Other Name: Cyclosporine/Neoral®/Sandimmune®/Gengraf®
Active Comparator: 2
Convert to Prograf (TAC) at target trough levels of 3.0-5.9 ng/mL.
 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).
Other Name: Tacrolimus/Prograf®/FK506
Active Comparator: 3
Convert to TAC at target trough levels of 6.0-8.9 ng/mL.
 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).
Other Name: Tacrolimus/Prograf®/FK506

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00905515

Locations
United States, North Carolina
Brody School of Medicine at East Carolina University
Greenville, North Carolina, United States, 27834
Sponsors and Collaborators
East Carolina University
Astellas Pharma US, Inc.
Investigators
Principal Investigator: Paul Bolin, MD East Carolina University
  More Information

Publications:

Responsible Party: Paul Bolin, Chair of Internal Medicine, East Carolina University
ClinicalTrials.gov Identifier: NCT00905515     History of Changes
Other Study ID Numbers: MR-06-001
Study First Received: May 18, 2009
Results First Received: October 22, 2012
Last Updated: January 4, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by East Carolina University:
Kidney Transplantation
Immunosuppressive Agents

Additional relevant MeSH terms:
Cyclosporins
Cyclosporine
Immunosuppressive Agents
Tacrolimus
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
 Immunologic Factors
Physiological Effects of Drugs
Antifungal Agents
Anti-Infective Agents
Therapeutic Uses
Dermatologic Agents
Antirheumatic Agents

ClinicalTrials.gov processed this record on May 21, 2013