Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients - Full Text View

Sponsor:	Pfizer
Information provided by (Responsible Party):	Pfizer
ClinicalTrials.gov Identifier:	NCT00895583

Purpose

This study will look at the effect on long-term kidney function using tacrolimus right after a transplant and then switching to sirolimus at 3 to 5 months after the transplant.

Condition	Intervention	Phase
Graft Rejection Kidney Transplant Renal Allograft Recipients Renal Transplant	Drug: Tacrolimus Drug: Sirolimus	Phase 4

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Prevention
Official Title:	Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients

Resource links provided by NLM:

MedlinePlus related topics: Kidney Transplantation

Drug Information available for: Sirolimus Tacrolimus Everolimus Temsirolimus

U.S. FDA Resources

Further study details as provided by Pfizer:

Primary Outcome Measures:

Percent of subjects who demonstrate a greater than or equal to 5 ml/min/1.73m2 improvement in calculated glomerular filtration rate (GFR). [ Time Frame: From randomization to 24 months post-transplant ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Composite rate of the first occurrence of biopsy-confirmed acute rejection (BCAR), graft loss, or death. [ Time Frame: From randomization to 24 months post-transplant ] [ Designated as safety issue: Yes ]

Enrollment:	256
Study Start Date:	June 2009
Estimated Study Completion Date:	August 2013
Estimated Primary Completion Date:	August 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Group I - Planned transition to sirolimus from tacrolimus	Drug: Tacrolimus During the screening phase, tacrolimus is provided by the investigator (not the Sponsor) and is dosed to achieve a target trough level determined by the investigator. Therefore, the dosage form, dosage, and frequency are determined by the investigator. Duration of treatment is from transplantation until randomization (from 90 to 150 days). Other Name: Prograf, Adagraf Drug: Sirolimus Following randomization, sirolimus is provided by the Sponsor in 1 and 2 mg oral tablets. Sirolimus is dosed once daily to achieve a target trough level of 7 to 15 ng/mL in the 1st year post-transplant and 5 - 15 ng/mL in the 2nd year post-transplant. Duration of treatment is from randomization through 2 years post-transplant (19 to 21 months). Other Name: Rapamune
Active Comparator: Group II - Continuation of tacrolimus	Drug: Tacrolimus During the study, tacrolimus is provided by the investigator (not the Sponsor) and is dosed to achieve a target trough level determined by the investigator. Therefore, the dosage form, dosage, and frequency are determined by the investigator. Duration of treatment is 2 years post-transplant. Other Name: Prograf, adagraf

Arms

Assigned Interventions

Experimental: Group I - Planned transition to sirolimus from tacrolimus

Drug: Tacrolimus

During the screening phase, tacrolimus is provided by the investigator (not the Sponsor) and is dosed to achieve a target trough level determined by the investigator. Therefore, the dosage form, dosage, and frequency are determined by the investigator. Duration of treatment is from transplantation until randomization (from 90 to 150 days).

Other Name: Prograf, Adagraf

Drug: Sirolimus

Following randomization, sirolimus is provided by the Sponsor in 1 and 2 mg oral tablets. Sirolimus is dosed once daily to achieve a target trough level of 7 to 15 ng/mL in the 1st year post-transplant and 5 - 15 ng/mL in the 2nd year post-transplant. Duration of treatment is from randomization through 2 years post-transplant (19 to 21 months).

Other Name: Rapamune

Active Comparator: Group II - Continuation of tacrolimus

Drug: Tacrolimus

During the study, tacrolimus is provided by the investigator (not the Sponsor) and is dosed to achieve a target trough level determined by the investigator. Therefore, the dosage form, dosage, and frequency are determined by the investigator. Duration of treatment is 2 years post-transplant.

Other Name: Prograf, adagraf

Eligibility

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

Criteria

Inclusion Criteria:

At Screening:

Male or female subjects aged 18 years or older.
Recipients who are 14 days prior to transplantation up through 14 days after transplantation.
Recipients of a primary, living- or deceased-donor renal allograft.
All female and male subjects who are biologically capable of having children must agree and commit to the use of a reliable method of birth control for the duration of the study and for 3 months after the last dose of test article. A subject is biologically capable of having children even if he or she is using contraceptives or if his or her sexual partner is sterile or using contraceptives.

At Randomization:

Ninety (90) to 150 days post-transplantation.
Treatment with tacrolimus and an inosine monophosphate dehydrogenase (IMPDH) inhibitor initiated less than or equal to 30 days of transplantation and has remained on both for the 30 days prior to randomization.

Exclusion Criteria:

At Screening:

Recipients of multiple organ transplants (i.e., any prior or concurrent transplantation of any organs including prior renal transplant. )
Recipients of adult or pediatric en bloc kidney transplants.
Recipients who required or will require desensitization protocols.
Known history of focal segmental glomerulosclerosis (FSGS) or membranoproliferative glomerulonephritis (MPGN).
Evidence of active systemic or localized major infection, as determined by the investigator.
Received any investigational drugs or devices less than or equal to 30 days prior to transplantation.
Known or suspected allergy to sirolimus (SRL), tacrolimus (TAC), inosine-monophosphate dehydrogenase (IMPDH) inhibitor, macrolide antibiotics, iothalamate, iodine, iodine-containing products, including contrast media other compounds related to these products/classes of medication, or shellfish.
History of malignancy less than or equal to 3 years of screening (except for adequately treated basal cell or squamous cell carcinoma of the skin).
Recipients who are known to be human immunodeficiency virus (HIV) positive.
Women who are biologically capable of having children with a positive urine or serum pregnancy test at screening.
Breastfeeding women.

At Randomization:

Any major illness/condition that, in the investigator's judgment, will substantially increase the risk associated with the subject's participation in and completion of the study, or could preclude the evaluation of the subject's response.
Planned treatment with immunosuppressive therapies other than those described in the protocol.
Subjects who underwent corticosteroids withdrawal or avoidance and did not receive antibody induction at the time of transplantation with anti-thymocyte globulin (rabbit) (rATG) (Thymoglobulin®), anti-thymocyte globulin (equine) (Atgam®), or alemtuzumab (Campath®).
Subjects who have had corticosteroid (CS) discontinued less than or equal to 30 days before randomization.
Calculated glomerular filtration rate (GFR) less than 40 mL/min/1.73m2 using the simplified Modification of Diet in Renal Disease (MDRD) formula less than or equal to 2 weeks prior to randomization.
Spot urine protein to creatinine ratio (UPr/Cr) greater than or equal to 0.5 less than or equal to 2 weeks prior to randomization.
Banff (2007) grade 2 or higher acute T-cell-mediated or any acute antibody-mediated rejection at any time post-transplantation.
Any acute rejection (biopsy-confirmed or presumed) less than or equal to 30 days before randomization.
More than 1 episode of acute rejection (biopsy-confirmed or presumed).
Known Banff (2007) interstitial fibrosis and tubular atrophy (IF/TA) greater than or equal to grade 2 or recurrent/de novo glomerular disease.
Major surgery less than or equal to 2 weeks prior to randomization.
Active post-operative complication, e.g. infection, delayed wound healing.
Total white blood cell count less than 2,000/mm3 or absolute neutrophil count (ANC) less than 1000 or platelet count less than 100,000/mm3 less than or equal to 2 weeks prior to randomization.
Fasting triglycerides greater than 400 mg/dL (greater than 4.5 mmol/L) or fasting total cholesterol greater than 300 mg/dL (greater than 7.8 mmol/L) less than or equal to 2 weeks prior to randomization regardless of whether or not on lipid-lowering therapy.
Women who are biologically capable of having children with a positive urine or serum pregnancy test at randomization.
Breastfeeding women.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00895583

Show 46 Study Locations

Sponsors and Collaborators

Pfizer

Investigators

Study Director:

Pfizer CT.gov Call Center

Pfizer

More Information

Additional Information:

To obtain contact information for a study center near you, click here. This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Pfizer
ClinicalTrials.gov Identifier:	NCT00895583 History of Changes
Other Study ID Numbers:	0468E8-4500, B1741007
Study First Received:	April 29, 2009
Last Updated:	May 17, 2012
Health Authority:	Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica Australia: Depart

Keywords provided by Pfizer:

renal transplant
immunosuppression
sirolimus/rapamune
planned transition

Additional relevant MeSH terms:

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 May 23, 2012