Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients

NCT00895583 | Completed Phase 4 Results

• 2 other identifiers: 0468E8-4500B1741007
• Study Type: interventional
• Target: 254
• Locations: 7 countries
• Sites: 44

Brief Summary

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.

Conditions

Graft Rejection; Kidney Transplant; Renal Allograft Recipients; Renal Transplant

Keywords

renal transplant; immunosuppression; sirolimus/rapamune; planned transition

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Improvement of Greater Than or Equal to [≥]5 Milliliters Per Minute Per 1.73 Square Meters (mL/Min/m^2) in Calculated Glomerular Filtration Rate (GFR) at 24 Months Post-Transplantation (On-Therapy Analysis)

  GFR was calculated using the Modified Diet in Renal Disease (MDRD) equation using either serum creatinine traceable to isotope dilution mass spectrometry (IDMS) or serum creatinine not traceable to IDMS.

  Baseline, Month 24

Secondary Outcomes (36)

• Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis)

  Baseline, Month 12

• Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation (Intent-to-Treat [ITT] Analysis)

  Baseline, Months 12 and 24

• Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation

  Baseline, Months 12 and 24

• Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation

  Baseline, Months 12 and 24

• Calculated GFR Using MDRD (On-Therapy Analysis)

  Baseline, Months 6, 12, 18, and 24

Study Arms (2)

Group I - Planned transition to sirolimus from tacrolimus

EXPERIMENTAL

Drug: Tacrolimus; Drug: Sirolimus

Group II - Continuation of tacrolimus

ACTIVE COMPARATOR

Drug: Tacrolimus

Interventions

Tacrolimus DRUG

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).

Also known as: Prograf, Adagraf

Group I - Planned transition to sirolimus from tacrolimus

Sirolimus DRUG

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).

Also known as: Rapamune

Group I - Planned transition to sirolimus from tacrolimus

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead

Study Sites (44)

Pfizer Investigational Site

La Jolla, California, 92037, United States

Location

Pfizer Investigational Site

San Francisco, California, 94115, United States

Location

Pfizer Investigational Site

Aurora, Colorado, 80045, United States

Location

Pfizer Investigational Site

Denver, Colorado, 80230, United States

Location

Pfizer Investigational Site

Atlanta, Georgia, 30309, United States

Location

Pfizer Investigational Site

Chicago, Illinois, 60611, United States

Location

Pfizer Investigational Site

Lexington, Kentucky, 40536, United States

Location

Pfizer Investigational Site

Portland, Maine, 04102, United States

Location

Pfizer Investigational Site

Boston, Massachusetts, 02215, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 48202, United States

Location

Pfizer Investigational Site

Detroit, Michigan, 48236, United States

Location

Pfizer Investigational Site

New York, New York, 10032, United States

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Pfizer Investigational Site

Rochester, New York, 14642, United States

Location

Pfizer Investigational Site

Chapel Hill, North Carolina, 27599 7155, United States

Location

Pfizer Investigational Site

Durham, North Carolina, 27705, United States

Location

Pfizer Investigational Site

Cincinnati, Ohio, 45267-0589, United States

Location

Pfizer Investigational Site

Cincinnati, Ohio, 45267-0595, United States

Location

Pfizer Investigational Site

Cleveland, Ohio, 44106, United States

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Portland, Oregon, 97239, United States

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Pfizer Investigational Site

Philadelphia, Pennsylvania, 19107, United States

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Pfizer Investigational Site

Charleston, South Carolina, 29425, United States

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Pfizer Investigational Site

Houston, Texas, 77030, United States

Location

Pfizer Investigational Site

Charlottesville, Virginia, 22901, United States

Location

Pfizer Investigational Site

Charlottesville, Virginia, 22908, United States

Location

Pfizer Investigational Site

Richmond, Virginia, 23298, United States

Location

Pfizer Investigational Site

Ciudad de Buenos Aires, Buenos Aires, C1425APQ, Argentina

Location

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Randwick, New South Wales, 2031, Australia

Location

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Adelaide, South Australia, 5000, Australia

Location

Pfizer Investigational Site

Nedlands, Western Australia, 6009, Australia

Location

Pfizer Investigational Site

Porto Alegre, Rio Grande do Sul, 90035-074, Brazil

Location

Pfizer Investigational Site

Bela Vista, São Paulo, 01323-030, Brazil

Location

Pfizer Investigational Site

São Paulo, São Paulo, 01323-000, Brazil

Location

Pfizer Investigational Site

São Paulo, São Paulo, 01323-001, Brazil

Location

Pfizer Investigational Site

São Paulo, São Paulo, 04038-002, Brazil

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Pfizer Investigational Site

São Paulo, São Paulo, 04039-033, Brazil

Location

Pfizer Investigational Site

Berlin, 10117, Germany

Location

Pfizer Investigational Site

Milan, Milano, 20162, Italy

Location

Pfizer Investigational Site

Milan, 20132, Italy

Location

Pfizer Investigational Site

Barcelona, Barcelona, 08036, Spain

Location

Pfizer Investigational Site

Madrid, Madrid, 28040, Spain

Location

Pfizer Investigational Site

Valencia, Valencia, 46026, Spain

Location

Pfizer Investigational Site

Barcelona, 08907, Spain

Location

Pfizer Investigational Site

Madrid, 28041, Spain

Location

Pfizer Investigational Site

Santander, 39008, Spain

Location

MeSH Terms

Interventions

Tacrolimus; Sirolimus

Intervention Hierarchy (Ancestors)

Macrolides; Lactones; Organic Chemicals

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 29, 2009
• First Posted: May 8, 2009
• Study Start: June 1, 2009
• Primary Completion: August 1, 2013
• Study Completion: August 1, 2013
• Last Updated: September 18, 2014
• Results First Posted: September 18, 2014

Record last verified: 2014-09

Locations

BR (6); AU (3); DE (1); ES (6); AR (1); US (25); IT (2)