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

Information source: Pfizer
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Graft Rejection; Kidney Transplant; Renal Allograft Recipients; Renal Transplant

Intervention: Tacrolimus (Drug); Sirolimus (Drug); Tacrolimus (Drug)

Phase: Phase 4

Status: Completed

Sponsored by: Pfizer

Official(s) and/or principal investigator(s):
Pfizer CT.gov Call Center, Study Director, Affiliation: Pfizer

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.

Clinical Details

Official title: Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Primary outcome: 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)

Secondary outcome:

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

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)

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

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

Calculated GFR Using MDRD (On-Therapy Analysis)

Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)

Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)

Serum Creatinine (On-Therapy Analysis)

Change From Randomization in Serum Creatinine (On-Therapy Analysis)

Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation

Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization

Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation

Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months

Number of Participants With BCAR by Severity of First BCAR and Time of Onset From Post-Randomization to 6, 12, 18, and 24 Months Post-Transplant

Percentage of Participants With Antibody Use in Treatment of Acute Rejection

Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia

Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L])

Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)

Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)

Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use

Percentage of Participants With Stomatitis

Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type

Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])

Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)

Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])

Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])

Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])

Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)

Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)

Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])

Percentage of Participants With New-Onset Diabetes

Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)

Percentage of Participants With Infection

Percentage of Participants With Cytomegalovirus (CMV) Infection

Percentage of Participants With Polyomavirus Infection

Percentage of Participants With Malignancy

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

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.

Locations and Contacts

Pfizer Investigational Site, Berlin 10117, Germany

Pfizer Investigational Site, Milano 20132, Italy

Pfizer Investigational Site, Milano 20162, Italy

Pfizer Investigational Site, Barcelona 08036, Spain

Pfizer Investigational Site, Barcelona 08907, Spain

Pfizer Investigational Site, Madrid 28040, Spain

Pfizer Investigational Site, Madrid 28041, Spain

Pfizer Investigational Site, Santander 39008, Spain

Pfizer Investigational Site, Valencia 46026, Spain

Pfizer Investigational Site, Ciudad de Buenos Aires, Buenos Aires C1425APQ, Argentina

Pfizer Investigational Site, La Jolla, California 92037, United States

Pfizer Investigational Site, San Francisco, California 94115, United States

Pfizer Investigational Site, Aurora, Colorado 80045, United States

Pfizer Investigational Site, Denver, Colorado 80230, United States

Pfizer Investigational Site, Atlanta, Georgia 30309, United States

Pfizer Investigational Site, Chicago, Illinois 60611, United States

Pfizer Investigational Site, Lexington, Kentucky 40536, United States

Pfizer Investigational Site, Portland, Maine 04102, United States

Pfizer Investigational Site, Boston, Massachusetts 02215, United States

Pfizer Investigational Site, Detroit, Michigan 48202, United States

Pfizer Investigational Site, Detroit, Michigan 48236, United States

Pfizer Investigational Site, Randwick, New South Wales 2031, Australia

Pfizer Investigational Site, New York, New York 10032, United States

Pfizer Investigational Site, Rochester, New York 14642, United States

Pfizer Investigational Site, Chapel Hill, North Carolina 27599 7155, United States

Pfizer Investigational Site, Durham, North Carolina 27705, United States

Pfizer Investigational Site, Cincinnati, Ohio 45267-0589, United States

Pfizer Investigational Site, Cincinnati, Ohio 45267-0595, United States

Pfizer Investigational Site, Cleveland, Ohio 44106, United States

Pfizer Investigational Site, Portland, Oregon 97239, United States

Pfizer Investigational Site, Philadelphia, Pennsylvania 19107, United States

Pfizer Investigational Site, Porto Alegre, RS 90035-074, Brazil

Pfizer Investigational Site, Sao Paulo, SP 01323-001, Brazil

Pfizer Investigational Site, Sao Paulo, SP 04038-002, Brazil

Pfizer Investigational Site, Sao Paulo, SP 04039-033, Brazil

Pfizer Investigational Site, Sao Paulo, SP 01323-000, Brazil

Pfizer Investigational Site, Bela Vista, Sao Paulo 01323-030, Brazil

Pfizer Investigational Site, Adelaide, South Australia 5000, Australia

Pfizer Investigational Site, Charleston, South Carolina 29425, United States

Pfizer Investigational Site, Houston, Texas 77030, United States

Pfizer Investigational Site, Charlottesville, Virginia 22901, United States

Pfizer Investigational Site, Charlottesville, Virginia 22908, United States

Pfizer Investigational Site, Richmond, Virginia 23298, United States

Pfizer Investigational Site, Nedlands, Western Australia 6009, Australia

Additional Information

To obtain contact information for a study center near you, click here.

Starting date: June 2009
Last updated: September 15, 2014

Page last updated: August 20, 2015

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