OPTIMAII: Optima: Optimizing Prograf Therapy in Maintenance Allografts II

• Sponsor: East Carolina University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00905515
• Collaborator: Astellas Pharma US, Inc. (Industry)
• Enrollment: 63
• Location: 1
• Arms: 3
• Duration (Months): 59
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Kidney Transplantation	Drug: cyclosporine; Drug: Prograf (Tacrolimus)	Phase 4

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 63 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optima: Optimizing Prograf Therapy in Maintenance Allografts II
• Study Start Date: Aug 1, 2003
• Actual Primary Completion Date: Jul 1, 2008
• Actual Study Completion Date: Jul 1, 2008

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Control Group Cyclosporine 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 Names: Cyclosporine/Neoral®/Sandimmune®/Gengraf®
Active Comparator: Low Trough Level Prograf Group 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 Names: Tacrolimus/Prograf®/FK506
Active Comparator: High Trough Level Prograf Group 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 Names: Tacrolimus/Prograf®/FK506

Outcome Measures

Primary Outcome Measures

1. Renal Function in Patients Converted From Cyclosporine to Prograf [3 years]

2. Optimal Dose of Calcineurin Inhibitor in Long-term Maintenance Kidney Transplant Patients [3 years]

3. Change in Risk Factors for Cardiovascular Morbidity and Chronic Graft Dysfunction as Evidenced by Blood Levels of Homocysteine [3 years]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.

• Responsible Party: Paul Bolin, Chair of Internal Medicine, East Carolina University
• ClinicalTrials.gov Identifier: NCT00905515
• Other Study ID Numbers: MR-06-001
• First Posted: May 20, 2009
• Last Update Posted: Jun 10, 2021
• Last Verified: Jun 1, 2021

• Keywords provided by Paul Bolin, Chair of Internal Medicine, East Carolina University: Kidney Transplantation; Immunosuppressive Agents
• Additional relevant MeSH terms: Cyclosporine; Tacrolimus; Cyclosporins

Study Results

Participant Flow

Arm/Group Title	Remaining on CsA	Reduced TAC	Standard TAC
Arm/Group Description	Stable transplant recipients randomly assigned to continue on Cyclosporine (CsA( with a target trough level of 50-250 ng/mL.	Stable transplant recipients randomly assigned to convert to "reduced" Tacrolimus (TAC) with target trough levels 3.0-5.9 ng/mL.	Stable transplant recipients randomly assigned to convert to "standard" TAC with target trough levels of 6.0-8.9 ng/mL.
Period Title: Overall Study
STARTED	21	20	22
COMPLETED	19	20	20
NOT COMPLETED	2	0	2

Baseline Characteristics

Arm/Group Title	Remaining on CsA	Reduced TAC	Standard TAC	Total
Arm/Group Description	Patients remained on CSA and were not converted to TAC.	Patients converted from CsA to TAC with trough concentrations 3.0-5.9 ng/mL	Patients were converted from CsA to TAC with trough concentrations of 6.0-8.9 ng/mL	Total of all reporting groups
Overall Participants	21	20	22	63
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	13 61.9%	16 80%	14 63.6%	43 68.3%
>=65 years	8 38.1%	4 20%	8 36.4%	20 31.7%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.65 (12.036)	58.57 (12.023)	59.14 (10.011)	58.48 (11.196)
Sex: Female, Male (Count of Participants)
Female	6 28.6%	10 50%	3 13.6%	19 30.2%
Male	15 71.4%	10 50%	19 86.4%	44 69.8%
Region of Enrollment (participants) [Number]
United States	21 100%	20 100%	22 100%	63 100%

Outcome Measures

1. Primary Outcome

Title	Renal Function in Patients Converted From Cyclosporine to Prograf
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remaining on CsA	Reduced TAC	Standard TAC
Arm/Group Description	Stable transplant recipients randomly assigned to continue on CSA with a target trough level of 50-250 ng/mL.	Stable transplant recipients randomly assigned to convert to "reduced" TAC with target trough levels 3.0-5.9 ng/mL.	Stable transplant recipients randomly assigned to convert to "standard" TAC with target trough levels of 6.0-8.9 ng/mL.
Measure Participants	21	20	22
Mean (Full Range) [Change in serum creatinine (mg/dL)]	0.05	0	0.10

2. Primary Outcome

Title	Optimal Dose of Calcineurin Inhibitor in Long-term Maintenance Kidney Transplant Patients
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remaining on CsA	Reduced TAC	Standard TAC
Arm/Group Description	Stable transplant recipients randomly assigned to continue on CSA with a target trough level of 50-250 ng/mL.	Stable transplant recipients randomly assigned to convert to "reduced" TAC with target trough levels 3.0-5.9 ng/mL.	Stable transplant recipients randomly assigned to convert to "standard" TAC with target trough levels of 6.0-8.9 ng/mL.
Measure Participants	21	20	22
Mean (Standard Deviation) [ng/dL]	130.2 (54.94)	5.24 (2.06)	6.90 (2.06)

3. Primary Outcome

Title	Change in Risk Factors for Cardiovascular Morbidity and Chronic Graft Dysfunction as Evidenced by Blood Levels of Homocysteine
Time Frame	3 years

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Remaining on CsA	Reduced TAC	Standard TAC
Arm/Group Description	Stable transplant recipients randomly assigned to continue on CSA with a target trough level of 50-250 ng/mL.	Stable transplant recipients randomly assigned to convert to "reduced" TAC with target trough levels 3.0-5.9 ng/mL.	Stable transplant recipients randomly assigned to convert to "standard" TAC with target trough levels of 6.0-8.9 ng/mL.
Measure Participants	21	20	22
Median (Standard Deviation) [ng/dL]	4.75 (0.82)	4.72 (0.52)	4.89 (0.33)

Adverse Events

Arm/Group Title	Remaining on CsA		Reduced TAC		Standard TAC
Arm/Group Description	Patients remained on CSA and were not converted to TAC.		Patients converted from CsA to TAC with trough concentrations 3.0-5.9 ng/mL		Patients were converted from CsA to TAC with trough concentrations of 6.0-8.9 ng/mL
All Cause Mortality
	Remaining on CsA		Reduced TAC		Standard TAC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Remaining on CsA		Reduced TAC		Standard TAC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/21 (0%)		2/20 (10%)		1/22 (4.5%)
Endocrine disorders
New onset diabetes mellitus	0/21 (0%)	0	1/20 (5%)	1	1/22 (4.5%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	0/21 (0%)	0	1/20 (5%)	1	0/22 (0%)	0
Other (Not Including Serious) Adverse Events
	Remaining on CsA		Reduced TAC		Standard TAC
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	11/21 (52.4%)		14/20 (70%)		14/22 (63.6%)
Blood and lymphatic system disorders
Anemia	1/21 (4.8%)	1	0/20 (0%)	0	1/22 (4.5%)	1
Absolute Neutrophil	1/21 (4.8%)	1	10/20 (50%)	11	10/22 (45.5%)	10
Cardiac disorders
Gingival Hypertrophy	1/21 (4.8%)	1	0/20 (0%)	0	0/22 (0%)	0
Endocrine disorders
Blood Glucose	7/21 (33.3%)	12	9/20 (45%)	23	8/22 (36.4%)	17
Hirsutism	0/21 (0%)	0	1/20 (5%)	1	0/22 (0%)	0
Musculoskeletal and connective tissue disorders
Bone Fracture	1/21 (4.8%)	1	0/20 (0%)	0	0/22 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.