Phase 4
Completed N=254
Study Evaluating A Planned Transition From Tacrolimus To Sirolimus In Kidney Transplant Recipients
graft rejection · Chronic Kidney Disease · Renal Allograft Recipients · Renal Transplant
Source: ClinicalTrials.gov NCT00895583 ↗
Enrolled (actual)
254
Serious AEs
34.7%
Results posted
Sep 2014
Primary outcomePrimary: 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) — 33.7; 42.2 percentage of participants — p=0.239
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.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| 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) |
33.7; 42.2 | 0.239 |
| SECONDARY Percentage of Participants With Improvement of ≥5 mL/Min/m^2 in Calculated GFR at 12 Months Post-Transplantation (On-Therapy Analysis) |
39.4; 44.8 | 0.422 |
| 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) |
38.2; 42.3; 33.6; 40.7 | 0.524 |
| SECONDARY Percentage of Participants With Improvement of ≥7.5 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation |
24.4; 35.8; 25.2; 30.9 | 0.055 |
| SECONDARY Percentage of Participants With Improvement of ≥10 mL/Min/m^2 in Calculated GFR at 12 and 24 Months Post-Transplantation |
19.8; 23.6; 22.1; 22.0 | 0.543 |
| SECONDARY Calculated GFR Using MDRD (On-Therapy Analysis) |
58.5; 57.4; 61.6; 57.6; 59.6; 61.3 | — |
| SECONDARY Change From Randomization in Calculated GFR Using MDRD (On-Therapy Analysis) |
2.7; 0.0; 1.5; 3.4; 2.2; 1.5 | 0.019 sig |
| SECONDARY Slope of Calculated GFR (MDRD) From Randomization to 24 Months Post-Transplantation (On-Therapy Analysis) |
-0.9; 0.9 | 0.131 |
| SECONDARY Serum Creatinine (On-Therapy Analysis) |
118.3; 117.7; 113.9; 117.0; 119.6; 109.4 | — |
| SECONDARY Change From Randomization in Serum Creatinine (On-Therapy Analysis) |
-4.1; -0.0; -0.3; -7.0; -3.0; -1.9 | 0.105 |
| SECONDARY Percentage of Participants With Biopsy-Confirmed Acute Rejection (BCAR), Graft Loss, or Death From Randomization to 24 Months Post-Transplantation |
11.5; 2.4 | 0.006 sig |
| SECONDARY Percentage of Participants With Graft Loss (Including Death) at 12 and 24 Months Post-Randomization |
0.8; 0.0; 3.8; 0.8 | 1.000 |
| SECONDARY Percentage of Participants With BCAR Post-Randomization to 6, 12, 18, and 24 Months Post-Transplantation |
1.5; 0.0; 5.3; 0.8; 6.9; 1.6 | 0.499 |
| SECONDARY Percentage of Participants With First On-Therapy BCAR From Transplantation Occurring at 12 and 24 Months |
5.1; 0.0; 9.3; 0.9 | — |
| 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 |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Percentage of Participants With Antibody Use in Treatment of Acute Rejection |
60.0; 75.0; 40.0; 25.0 | 1.000 |
| SECONDARY Percentage of Participants With Anemia, Thrombocytopenia, or Leukopenia |
4.6; 1.6; 9.1; 2.6; 3.4; 4.5 | 0.284 |
| SECONDARY Change From Baseline (Pre-Randomization) to 12 and 24 Months Post-Transplantation in Fasting Lipid Parameters (Millimoles Per Liter [mmol/L]) |
0.66; -0.12; 0.51; -0.08; -0.00; 0.01 | <0.001 sig |
| SECONDARY Percentage of Participants Requiring Anti-Hypertensive Medication, Diabetes Agents, Lipid-Lowering Agents, or Erythropoiesis Stimuating Agents (ESAs) |
95.4; 92.7; 75.6; 69.9; 61.8; 65.9 | 0.429 |
| SECONDARY Spot and 24 Hour Urine Protein to Creatinine Ratio (UPr/Cr) |
0.180; 0.195; 0.353; 0.208; 0.510; 0.300 | <0.001 sig |
| SECONDARY Percentage of Participants With Angiotensin Converting Enzyme Inhibitor (ACEI) or Angiotensin II Receptor Block (ARB) Use |
46.6; 46.3; 43.5; 29.3; 32.1; 18.7 | 1.000 |
| SECONDARY Percentage of Participants With Stomatitis |
28.2; 1.6 | <0.001 sig |
| SECONDARY Percentage of Participants Requiring Treatment for Stomatitis by Treatment Type |
17.6; 2.4; 3.1; 1.6; 0.8; 0.0 | <0.001 sig |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Hemoglobin A1C (Liter Per Liter [L/L]) |
-0.00; 0.00 | 0.521 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Glucose (mmol/L) |
-0.50; -0.23 | 0.265 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Fasting Insulin (Picomoles Per Liter [Pmol/L]) |
27.25; 17.14 | 0.672 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Weight (Kilograms [kg]) |
1.61; 2.03 | 0.504 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Waist Circumference(Centimeters [cm]) |
1.13; 2.21 | 0.637 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Homeostasis Model Assessment Insulin Resistance (HOMA-IR; Fasting) |
1.14; 1.10 | 0.955 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in HOMA-Beta Cell (HOMA-B; Fasting) |
230.23; 26.05 | 0.279 |
| SECONDARY Change From Pre-Randomization to 12 Months Post-Transplantation in Body Mass Index (BMI; in Kilograms Per Square Meter [kg/m^2]) |
0.53; 0.75 | 0.337 |
| SECONDARY Percentage of Participants With New-Onset Diabetes |
18.3; 5.6; 14.6; 2.8; 4.3; 2.9 | 0.025 sig |
| SECONDARY Percentage of Participants With New-Onset Diabetes Receiving Treatment for Diabetes (Insulin and Non-Insulin) |
13.3; 0.0; 6.7; 25.0; 13.3; 0.0 | 1.000 |
| SECONDARY Percentage of Participants With Infection |
61.8; 52.0 | 0.129 |
| SECONDARY Percentage of Participants With Cytomegalovirus (CMV) Infection |
3.1; 3.3 | 1.000 |
| SECONDARY Percentage of Participants With Polyomavirus Infection |
3.8; 7.3 | 0.276 |
| SECONDARY Percentage of Participants With Malignancy |
3.1; 7.3 | 0.158 |
Eligibility 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 co
Data sourced from ClinicalTrials.gov (NCT00895583). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication. Informational only — not medical advice.