Graft RejectionPhase 4NCT00895583
Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients
A Phase 4 study testing Tacrolimus and Sirolimus in people with Graft Rejection and Kidney Transplant, run by Pfizer at 44 sites in 7 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Graft Rejection, Kidney Transplant, Renal Allograft Recipients
- What is being tested?
- Tacrolimus and Sirolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 254 participants
- Where
- 44 sitesin 7 countries
- Study dates
- Jun 2009to Aug 2013
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Show all 29Show fewer
- 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.
Trial locations and contacts
44 sites in 7 countries.
44 sites in 7 countries
United States25 sites
Pfizer Investigational Site
Atlanta, Georgia, 30309
Pfizer Investigational Site
Aurora, Colorado, 80045
Pfizer Investigational Site
Boston, Massachusetts, 02215
Pfizer Investigational Site
Chapel Hill, North Carolina, 27599 7155
Pfizer Investigational Site
Charleston, South Carolina, 29425
Pfizer Investigational Site
Charlottesville, Virginia, 22901
Pfizer Investigational Site
Charlottesville, Virginia, 22908
Pfizer Investigational Site
Chicago, Illinois, 60611
Pfizer Investigational Site
Cincinnati, Ohio, 45267-0589
Pfizer Investigational Site
Cincinnati, Ohio, 45267-0595
Pfizer Investigational Site
Cleveland, Ohio, 44106
Pfizer Investigational Site
Denver, Colorado, 80230
Pfizer Investigational Site
Detroit, Michigan, 48202
Pfizer Investigational Site
Detroit, Michigan, 48236
Pfizer Investigational Site
Durham, North Carolina, 27705
Pfizer Investigational Site
Houston, Texas, 77030
Pfizer Investigational Site
La Jolla, California, 92037
Pfizer Investigational Site
Lexington, Kentucky, 40536
Pfizer Investigational Site
New York, New York, 10032
Pfizer Investigational Site
Philadelphia, Pennsylvania, 19107
Pfizer Investigational Site
Portland, Maine, 04102
Pfizer Investigational Site
Portland, Oregon, 97239
Pfizer Investigational Site
Richmond, Virginia, 23298
Pfizer Investigational Site
Rochester, New York, 14642
Pfizer Investigational Site
San Francisco, California, 94115
Brazil6 sites
Pfizer Investigational Site
Bela Vista, São Paulo, 01323-030
Pfizer Investigational Site
Porto Alegre, Rio Grande do Sul, 90035-074
Pfizer Investigational Site
São Paulo, São Paulo, 01323-000
Pfizer Investigational Site
São Paulo, São Paulo, 01323-001
Pfizer Investigational Site
São Paulo, São Paulo, 04038-002
Pfizer Investigational Site
São Paulo, São Paulo, 04039-033
Spain6 sites
Pfizer Investigational Site
Barcelona, Barcelona, 08036
Pfizer Investigational Site
Barcelona, 08907
Pfizer Investigational Site
Madrid, Madrid, 28040
Pfizer Investigational Site
Madrid, 28041
Pfizer Investigational Site
Santander, 39008
Pfizer Investigational Site
Valencia, Valencia, 46026
Australia3 sites
Pfizer Investigational Site
Adelaide, South Australia, 5000
Pfizer Investigational Site
Nedlands, Western Australia, 6009
Pfizer Investigational Site
Randwick, New South Wales, 2031
Italy2 sites
Pfizer Investigational Site
Milan, Milano, 20162
Pfizer Investigational Site
Milan, 20132
Argentina1 site
Pfizer Investigational Site
Ciudad de Buenos Aires, Buenos Aires, C1425APQ
About this study
Official title: Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients
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.
- Being tested
- Tacrolimus, Sirolimus
- Keywords
- renal transplant, immunosuppression, sirolimus/rapamune, planned transition
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TacrolimusDrug
Also called Prograf, Adagraf
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).
SirolimusDrug
Also called Rapamune
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).
TacrolimusDrug
Also called Prograf, adagraf
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.
| Study group | Role | What they receive |
|---|---|---|
| Group I - Planned transition to sirolimus from tacrolimus | Experimental | Not described Receives: Drug: Tacrolimus; Drug: Sirolimus |
| Group II - Continuation of tacrolimus | Active comparator | Not described Receives: Drug: Tacrolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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)
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.
Measured: 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)
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.
Measured: 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
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.
Measured: 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
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS.
Measured: Baseline, Months 12 and 24
Calculated GFR Using MDRD (On-Therapy Analysis)
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.
Measured: Baseline, Months 6, 12, 18, and 24
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.
Measured: Baseline, Months 6, 12, 18, and 24
Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)
GFR was calculated using the MDRD equation using either serum creatinine traceable to IDMS or serum creatinine not traceable to IDMS. Timepoints were calculated as study days, relative to the time of randomization of study medication. All available on-therapy values were included. Observed data were multiplied by a scale factor of 365, expressing the slope as an annual change.
Measured: Baseline, Month 24
Serum Creatinine (On-Therapy Analysis)
Serum creatinine was measured in micromillimoles per liter (mcmol/L). Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.
Measured: Baseline, Months 6, 12, 18, and 24
Change From Randomization in Serum Creatinine (On-Therapy Analysis)
Serum creatinine was measured in mcmol/L. Baseline was defined as the last assessment prior to first administration of study drug.
Measured: Baseline, Months 6, 12, 18, and 24
Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation
Biopsy-confirmed acute rejection was defined according to updated Banff criteria (2007) for renal allograft rejection. Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for greater than or equal to [≥]56 days with no return of graft function), or death.
Measured: Post-randomization to Month 24 post-transplantation
Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization
Graft loss was defined as physical loss (nephrectomy or retransplantation), functional loss (requiring dialysis for ≥56 days with no return of graft function), or death.
Measured: Post-randomization to Months 12 and 24 Post-Transplantation
Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation
BCAR was defined according to updated Banff criteria (2007) for renal allograft rejection.
Measured: 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
Defined as the first BCAR occurring during the On-Therapy period based on the ITT population. Time to first BCAR was the days from transplantation to the date of BCAR.
Measured: Months 12 and 24
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
BCAR was categorized as antibody-mediated (AM) or T-cell. AM BCAR severity was graded as Grade I (mild), Grade II (moderate), and Grade III (severe). T-cell BCAR severity was graded as 'Grade Ia, Ib (mild), Grade IIa, IIb (moderate), and Grade III (severe). If a participant had both T-cell BCAR and antibody-mediated BCAR on the first rejection, the participant was counted in each category.
Measured: Months 6, 12, 18, and 24
Percentage of Participants With Antibody Use in Treatment of Acute Rejection
Number of participants who experienced an adverse event (AE) of rejection was used as the denominator in the determination of percentage of participants with antibody use in treatment of acute rejection.
Measured: On Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia
Anemia was defined as hemoglobin less than or equal to (≤)10 grams per deciliter (g/dL); leukopenia was defined as white blood cell (WBC) count ≤2000 per cubic millimeters (/mm^3); and thrombocytopenia was defined as platelets ≤100,000/mm^3. Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.
Measured: Baseline, Months 12 and 24
Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L])
Parameters assessed included total cholesterol (TC), triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C); collected when participant was in a fasting state.
Measured: Baseline, Months 12 and 24
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)
Measured: Baseline, Months 12 and 24
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)
Baseline was defined as the last nonmissing assessment before or on the date of the first dose of test article.
Measured: Baseline and Months 12 and 24
Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use
Included ACEI or ARB use prior to randomization, during the on-therapy period (up to 19 to 21 months post randomization) and the off-therapy period (up to 24 months post-transplantation).
Measured: Pre-randomization, On-Therapy Period (up to 21 months post-randomization), and Off-Therapy Period (up to 24 months post-transplantation)
Percentage of Participants With Stomatitis
Includes adverse events based on categorization by the investigator as stomatitis, regardless of the event preferred term in Medical Dictionary for Regulatory Activities (MedDRA)
Measured: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type
Included treatments (analgesics, dental paste, topical antifungal, topical steroids, or other) prior to randomization, during the on-therapy period (up to 19 to 21 months post-randomization) and the off-therapy period (up to 24 months post-transplantation).
Measured: On-Therapy Period (up to 21 months post-randomization) and Off-Therapy Period (up to 24 months post-transplantation)
Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])
Ratio of hemoglobin A1c to normal hemoglobin.
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)
The HOMA-IR measures insulin resistance based on fasting glucose and insulin measurements:
HOMA-IR = fasting plasma glucose (mmol/L) multiplied by (*) fasting plasma insulin in microunits per liter (µU/L) divided by (/) 22.5.
Participants taking insulin within 12 hours were excluded from the analysis.
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)
The Homeostasis Model Assessment (HOMA) estimates steady state beta cell function (%B) as a percentage of a normal reference population.
HOMA-B = 20 * insulin (µU/L) / fasting plasma glucose (mmol/L) minus (-) 3.5 Participants taking insulin within 12 hours were excluded from the analysis.
Measured: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2])
BMI = Weight (kg)/(Height*Height) (square meters [m^2]).
Measured: Baseline, Month 12
Percentage of Participants With New-Onset Diabetes
Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged from baseline to Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose greater than or equal to (≥)126 milligrams per deciliter (mg/dL) after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization, were included in the new-onset diabetes population. Events at Months 12 or 24 occurred from baseline to On-therapy Month 12 and from On-therapy Months 12 to 24, respectively.
Measured: 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
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)
Participants were considered as having new onset diabetes during the On-therapy period if any of the below events emerged between baseline and Month 12 or Month 24: 1) at least 30 days continuous, or at least 25 days non-stop (without gap) use of any diabetic treatment after randomization; 2) a fasting glucose ≥126 mg/dL after randomization; or 3) a non-fasting glucose ≥200 mg/dL after randomization.
Measured: 12 Months and 24 Months
Percentage of Participants With Infection
Includes adverse events based on categorization by the investigator as 'infection', regardless of the event preferred term in MedDRA.
Measured: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Cytomegalovirus (CMV) Infection
Includes adverse event terms reported by the investigator to be attributed to the organism 'cytomegalovirus', regardless of the preferred term in MedDRA.
Measured: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Polyomavirus Infection
Includes adverse event terms reported by the investigator to be attributed to the organism 'polyomavirus', regardless of the preferred term in MedDRA.
Measured: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Malignancy
Includes any adverse events based on categorization by the investigator as 'malignancy', regardless of the event preferred term in MedDRA.
Measured: From randomization up to 24 months after transplantation (On-Therapy)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2009 (estimated)
- Study startJun 2009
- Primary completionAug 2013
- Study completionAug 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Graft RejectionStudies of the same condition, open and under way.
- More trials run by PfizerThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 254 participants (actual)
Sponsor and investigators
- Lead sponsor
- Pfizer
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Pfizer CT.gov Call Center, Study director, Pfizer
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00895583
- Sponsor's protocol ID
- 0468E8-4500
- Other IDs
- B1741007
- Status last verified
- Sep 2014
- First submitted
- 29 Apr 2009
- Last updated
- 18 Sep 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Planned Transition To Sirolimus-Based Therapy Versus Continued Tacrolimus-Based Therapy In Renal Allograft Recipients
- ClinicalTrials.gov ID
- NCT00895583
- Acronym / sponsor ID
- 0468E8-4500
- Keywords
- renal transplant, immunosuppression, sirolimus/rapamune, planned transition
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 254 participants (actual)
- Lead sponsor
- PfizerIndustry (pharma, biotech, devices)
- Study start
- Jun 2009
- Primary completion
- Aug 2013 (actual)
- Study completion
- Aug 2013 (actual)
- First posted
- 8 May 2009 (estimated)
- Results
- Posted 18 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group I - Planned transition to sirolimus from tacrolimus | Experimental | Drug: Tacrolimus, Drug: Sirolimus |
| Group II - Continuation of tacrolimus | Active comparator | Drug: Tacrolimus |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
- Ninety (90) to 150 days post-transplantation.
Key exclusion criteria (29 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| TacrolimusAlso: Prograf, AdagrafDuring 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). | Drug | Group I - Planned transition to sirolimus from tacrolimus |
| SirolimusAlso: RapamuneFollowing 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). | Drug | Group I - Planned transition to sirolimus from tacrolimus |
| TacrolimusAlso: Prograf, adagrafDuring 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. | Drug | Group II - Continuation of tacrolimus |
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)
Time frame: Baseline, Month 24
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.
36 secondary outcomes
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
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
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
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
Calculated GFR Using MDRD (On-Therapy Analysis)
Time frame: Baseline, Months 6, 12, 18, and 24
Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis)
Time frame: Baseline, Months 6, 12, 18, and 24
Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis)
Time frame: Baseline, Month 24
Serum Creatinine (On-Therapy Analysis)
Time frame: Baseline, Months 6, 12, 18, and 24
Change From Randomization in Serum Creatinine (On-Therapy Analysis)
Time frame: Baseline, Months 6, 12, 18, and 24
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
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
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
Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months
Time frame: Months 12 and 24
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
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)
Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia
Time frame: Baseline, Months 12 and 24
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
Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs)
Time frame: Baseline, Months 12 and 24
Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr)
Time frame: Baseline and Months 12 and 24
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)
Percentage of Participants With Stomatitis
Time frame: From randomization up to 24 months after transplantation (On-Therapy)
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)
Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L])
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L)
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L])
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg])
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm])
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting)
Time frame: Baseline, Month 12
Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting)
Time frame: Baseline, Month 12
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
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
Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin)
Time frame: 12 Months and 24 Months
Percentage of Participants With Infection
Time frame: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Cytomegalovirus (CMV) Infection
Time frame: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Polyomavirus Infection
Time frame: From randomization up to 24 months after transplantation (On-Therapy)
Percentage of Participants With Malignancy
Time frame: From randomization up to 24 months after transplantation (On-Therapy)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Sep 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Graft Rejection
RecruitingPhase 1
Treatment of Antibody-Mediated Rejection (ABMR) With CarBel
Kidney Transplant Rejection
RecruitingPhase 2
A Study to Learn About the Effects of Felzartamab Infusions in Adults With Kidney Transplants Who Have Late Isolated Microvascular Inflammation
Microvascular Inflammation
Recruiting
Efficiency of Everolimus for the Treatment of Kidney Transplanted Patients Presenting a Missing Self-induced NK-mediated Rejection
Kidney Transplant Failure and Rejection
RecruitingObservational study
Magnetic Resonance Elastography as a Method to Estimate Stiffness of Soft Tissues
Heart Failure, Liver Fibrosis
Enrolling by invitationObservational study
GEnomic Medicine in Kidney Transplantation Study
Transplant Complication, Kidney Transplant Rejection
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Pfizer CT.gov Call Center study director
Pfizer
44 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Tacrolimus and Sirolimus in people with Graft Rejection and Kidney Transplant, run by Pfizer at 44 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Sep 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 44 sites in United States, Brazil, Spain, Australia, Italy and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 18 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Sep 2014.