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Trial record 1 of 1 for:    NCT00895583
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Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT00895583
First received: April 29, 2009
Last updated: September 15, 2014
Last verified: September 2014
Results First Received: July 23, 2014  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Prevention
Conditions: Graft Rejection
Kidney Transplant
Renal Allograft Recipients
Renal Transplant
Interventions: Drug: Tacrolimus
Drug: Sirolimus

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
No text entered.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Sirolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center’s standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Tacrolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center’s standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.

Participant Flow:   Overall Study
    Sirolimus     Tacrolimus  
STARTED     131     123  
COMPLETED     87     111  
NOT COMPLETED     44     12  
Adverse Event                 28                 4  
Death                 2                 1  
Physician Decision                 3                 1  
Lost to Follow-up                 1                 3  
Protocol Violation                 1                 0  
Withdrawal by Subject                 4                 2  
Lack of Efficacy                 5                 0  
Not specified                 0                 1  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Safety Population: all randomized participants who received at least one dose of the assigned therapy after randomization.

Reporting Groups
  Description
Sirolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center’s standard of care. At 3-5 months post-transplant, participants were randomized, tacrolimus was discontinued (withdrawal was to be completed within 2 weeks [maximum of 4 weeks] of sirolimus initiation) and participants received sirolimus tablets, orally, at a dose to achieve trough levels of 7-15 nanograms per milliliter (ng/mL) during the first year post-transplant, then 5-15 ng/mL. Participants remained on an inosine monophosphate dehydrogenase (IMPDH) inhibitor (mycophenolate mofetil [MMF] or mycophenolate sodium [MPS]; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 milligrams per day (mg/day) of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Tacrolimus Participants received tacrolimus (extended-release formulation not permitted) within 30 days of transplant, dosed according to center’s standard of care. At 3-5 months post-transplant, participants were randomized and tacrolimus continued. Participants remained on an IMPDH inhibitor (MMF or MPS; switching between the two was permitted). Corticosteroids were maintained at a minimum of 2.5 mg/day of prednisone (or equivalent); withdrawal was prohibited after randomization. Participants received study drug during the post-randomization period for up to a maximum of 18 months post-transplant.
Total Total of all reporting groups

Baseline Measures
    Sirolimus     Tacrolimus     Total  
Number of Participants  
[units: participants]
  131     123     254  
Age  
[units: years]
Mean ± Standard Deviation
  50.7  ± 13.03     52.4  ± 12.05     51.5  ± 12.57  
Gender  
[units: participants]
     
Female     42     46     88  
Male     89     77     166  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   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)   [ Time Frame: Baseline, Month 24 ]

2.  Secondary:   Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis)   [ Time Frame: Baseline, Month 12 ]

3.  Secondary:   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)   [ Time Frame: Baseline, Months 12 and 24 ]

4.  Secondary:   Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation   [ Time Frame: Baseline, Months 12 and 24 ]

5.  Secondary:   Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation   [ Time Frame: Baseline, Months 12 and 24 ]

6.  Secondary:   Calculated GFR Using MDRD (On-Therapy Analysis)   [ Time Frame: Baseline, Months 6, 12, 18, and 24 ]

7.  Secondary:   Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)   [ Time Frame: Baseline, Months 6, 12, 18, and 24 ]

8.  Secondary:   Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)   [ Time Frame: Baseline, Month 24 ]

9.  Secondary:   Serum Creatinine (On-Therapy Analysis)   [ Time Frame: Baseline, Months 6, 12, 18, and 24 ]

10.  Secondary:   Change From Randomization in Serum Creatinine (On-Therapy Analysis)   [ Time Frame: Baseline, Months 6, 12, 18, and 24 ]

11.  Secondary:   Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation   [ Time Frame: Post-randomization to Month 24 post-transplantation ]

12.  Secondary:   Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization   [ Time Frame: Post-randomization to Months 12 and 24 Post-Transplantation ]

13.  Secondary:   Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation   [ Time Frame: Post-Randomization to 6, 12, 18, and 24 months Post-Transplantation ]

14.  Secondary:   Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months   [ Time Frame: Months 12 and 24 ]

15.  Secondary:   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   [ Time Frame: Months 6, 12, 18, and 24 ]

16.  Secondary:   Percentage of Participants With Antibody Use in Treatment of Acute Rejection   [ Time Frame: On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation) ]

17.  Secondary:   Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia   [ Time Frame: Baseline, Months 12 and 24 ]

18.  Secondary:   Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L])   [ Time Frame: Baseline, Months 12 and 24 ]

19.  Secondary:   Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)   [ Time Frame: Baseline, Months 12 and 24 ]

20.  Secondary:   Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)   [ Time Frame: Baseline and Months 12 and 24 ]

21.  Secondary:   Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use   [ Time Frame: Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation) ]

22.  Secondary:   Percentage of Participants With Stomatitis   [ Time Frame: From randomization up to 24 months after transplantation (On-Therapy) ]

23.  Secondary:   Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type   [ Time Frame: On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation) ]

24.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])   [ Time Frame: Baseline, Month 12 ]

25.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)   [ Time Frame: Baseline, Month 12 ]

26.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])   [ Time Frame: Baseline, Month 12 ]

27.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])   [ Time Frame: Baseline, Month 12 ]

28.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])   [ Time Frame: Baseline, Month 12 ]

29.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)   [ Time Frame: Baseline, Month 12 ]

30.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)   [ Time Frame: Baseline, Month 12 ]

31.  Secondary:   Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])   [ Time Frame: Baseline, Month 12 ]

32.  Secondary:   Percentage of Participants With New-Onset Diabetes   [ Time Frame: From Baseline to On-Therapy Month 12, from Baseline to On-Therapy Month 24, and from On-Therapy Month 12 up to On-Therapy Month 24 ]

33.  Secondary:   Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)   [ Time Frame: 12 Months and 24 Months ]

34.  Secondary:   Percentage of Participants With Infection   [ Time Frame: From randomization up to 24 months after transplantation (On-Therapy) ]

35.  Secondary:   Percentage of Participants With Cytomegalovirus (CMV) Infection   [ Time Frame: From randomization up to 24 months after transplantation (On-Therapy) ]

36.  Secondary:   Percentage of Participants With Polyomavirus Infection   [ Time Frame: From randomization up to 24 months after transplantation (On-Therapy) ]

37.  Secondary:   Percentage of Participants With Malignancy   [ Time Frame: From randomization up to 24 months after transplantation (On-Therapy) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
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  More Information
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Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS 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.
The agreement is:
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
unchecked The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.


Results Point of Contact:  
Name/Title: Pfizer ClinicalTrials.gov Call Center
Organization: Pfizer, Inc.
phone: 1-800-718-1021
e-mail: ClinicalTrials.gov_Inquiries@pfizer.com


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
Results First Received: July 23, 2014
Last Updated: September 15, 2014
Health Authority: Argentina: Administracion Nacional de Medicamentos, Alimentos y Tecnologia Medica
Australia: Depart