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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT00895583




Registration number
NCT00895583
Ethics application status
Date submitted
29/04/2009
Date registered
8/05/2009
Date last updated
18/09/2014

Titles & IDs
Public title
Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients
Scientific title
Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients
Secondary ID [1] 0 0
B1741007
Secondary ID [2] 0 0
0468E8-4500
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Graft Rejection 0 0
Kidney Transplant 0 0
Renal Allograft Recipients 0 0
Renal Transplant 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Tacrolimus
Treatment: Drugs - Sirolimus
Treatment: Drugs - Tacrolimus

Experimental: Group I - Planned transition to sirolimus from tacrolimus -

Active comparator: Group II - Continuation of tacrolimus -


Treatment: Drugs: 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).

Treatment: Drugs: 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).

Treatment: Drugs: 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.

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
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)
Timepoint [1] 0 0
Baseline, Month 24
Secondary outcome [1] 0 0
Percentage of Participants With Improvement of =5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis)
Timepoint [1] 0 0
Baseline, Month 12
Secondary outcome [2] 0 0
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)
Timepoint [2] 0 0
Baseline, Months 12 and 24
Secondary outcome [3] 0 0
Percentage of Participants With Improvement of =7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation
Timepoint [3] 0 0
Baseline, Months 12 and 24
Secondary outcome [4] 0 0
Percentage of Participants With Improvement of =10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation
Timepoint [4] 0 0
Baseline, Months 12 and 24
Secondary outcome [5] 0 0
Calculated GFR Using MDRD (On-Therapy Analysis)
Timepoint [5] 0 0
Baseline, Months 6, 12, 18, and 24
Secondary outcome [6] 0 0
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)
Timepoint [6] 0 0
Baseline, Months 6, 12, 18, and 24
Secondary outcome [7] 0 0
Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)
Timepoint [7] 0 0
Baseline, Month 24
Secondary outcome [8] 0 0
Serum Creatinine (On-Therapy Analysis)
Timepoint [8] 0 0
Baseline, Months 6, 12, 18, and 24
Secondary outcome [9] 0 0
Change From Randomization in Serum Creatinine (On-Therapy Analysis)
Timepoint [9] 0 0
Baseline, Months 6, 12, 18, and 24
Secondary outcome [10] 0 0
Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation
Timepoint [10] 0 0
Post-randomization to Month 24 post-transplantation
Secondary outcome [11] 0 0
Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization
Timepoint [11] 0 0
Post-randomization to Months 12 and 24 Post-Transplantation
Secondary outcome [12] 0 0
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation
Timepoint [12] 0 0
Post-Randomization to 6, 12, 18, and 24 months Post-Transplantation
Secondary outcome [13] 0 0
Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months
Timepoint [13] 0 0
Months 12 and 24
Secondary outcome [14] 0 0
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
Timepoint [14] 0 0
Months 6, 12, 18, and 24
Secondary outcome [15] 0 0
Percentage of Participants With Antibody Use in Treatment of Acute Rejection
Timepoint [15] 0 0
On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)
Secondary outcome [16] 0 0
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia
Timepoint [16] 0 0
Baseline, Months 12 and 24
Secondary outcome [17] 0 0
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L])
Timepoint [17] 0 0
Baseline, Months 12 and 24
Secondary outcome [18] 0 0
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)
Timepoint [18] 0 0
Baseline, Months 12 and 24
Secondary outcome [19] 0 0
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)
Timepoint [19] 0 0
Baseline and Months 12 and 24
Secondary outcome [20] 0 0
Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use
Timepoint [20] 0 0
Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation)
Secondary outcome [21] 0 0
Percentage of Participants With Stomatitis
Timepoint [21] 0 0
From randomization up to 24 months after transplantation (On-Therapy)
Secondary outcome [22] 0 0
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type
Timepoint [22] 0 0
On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)
Secondary outcome [23] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])
Timepoint [23] 0 0
Baseline, Month 12
Secondary outcome [24] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)
Timepoint [24] 0 0
Baseline, Month 12
Secondary outcome [25] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])
Timepoint [25] 0 0
Baseline, Month 12
Secondary outcome [26] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])
Timepoint [26] 0 0
Baseline, Month 12
Secondary outcome [27] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])
Timepoint [27] 0 0
Baseline, Month 12
Secondary outcome [28] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)
Timepoint [28] 0 0
Baseline, Month 12
Secondary outcome [29] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)
Timepoint [29] 0 0
Baseline, Month 12
Secondary outcome [30] 0 0
Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])
Timepoint [30] 0 0
Baseline, Month 12
Secondary outcome [31] 0 0
Percentage of Participants With New-Onset Diabetes
Timepoint [31] 0 0
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
Secondary outcome [32] 0 0
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)
Timepoint [32] 0 0
12 Months and 24 Months
Secondary outcome [33] 0 0
Percentage of Participants With Infection
Timepoint [33] 0 0
From randomization up to 24 months after transplantation (On-Therapy)
Secondary outcome [34] 0 0
Percentage of Participants With Cytomegalovirus (CMV) Infection
Timepoint [34] 0 0
From randomization up to 24 months after transplantation (On-Therapy)
Secondary outcome [35] 0 0
Percentage of Participants With Polyomavirus Infection
Timepoint [35] 0 0
From randomization up to 24 months after transplantation (On-Therapy)
Secondary outcome [36] 0 0
Percentage of Participants With Malignancy
Timepoint [36] 0 0
From randomization up to 24 months after transplantation (On-Therapy)

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,SA,WA
Recruitment hospital [1] 0 0
Pfizer Investigational Site - Randwick
Recruitment hospital [2] 0 0
Pfizer Investigational Site - Adelaide
Recruitment hospital [3] 0 0
Pfizer Investigational Site - Nedlands
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
5000 - Adelaide
Recruitment postcode(s) [3] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Georgia
Country [4] 0 0
United States of America
State/province [4] 0 0
Illinois
Country [5] 0 0
United States of America
State/province [5] 0 0
Kentucky
Country [6] 0 0
United States of America
State/province [6] 0 0
Maine
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
New York
Country [10] 0 0
United States of America
State/province [10] 0 0
North Carolina
Country [11] 0 0
United States of America
State/province [11] 0 0
Ohio
Country [12] 0 0
United States of America
State/province [12] 0 0
Oregon
Country [13] 0 0
United States of America
State/province [13] 0 0
Pennsylvania
Country [14] 0 0
United States of America
State/province [14] 0 0
South Carolina
Country [15] 0 0
United States of America
State/province [15] 0 0
Texas
Country [16] 0 0
United States of America
State/province [16] 0 0
Virginia
Country [17] 0 0
Argentina
State/province [17] 0 0
Buenos Aires
Country [18] 0 0
Brazil
State/province [18] 0 0
RS
Country [19] 0 0
Brazil
State/province [19] 0 0
Sao Paulo
Country [20] 0 0
Brazil
State/province [20] 0 0
SP
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Italy
State/province [22] 0 0
Milano
Country [23] 0 0
Spain
State/province [23] 0 0
Barcelona
Country [24] 0 0
Spain
State/province [24] 0 0
Madrid
Country [25] 0 0
Spain
State/province [25] 0 0
Santander
Country [26] 0 0
Spain
State/province [26] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Pfizer
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Pfizer CT.gov Call Center
Address 0 0
Pfizer
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.