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- Essai clinique NCT00543569
A Study to Assess the Safety and Efficacy of Alefacept in Kidney Transplant Recipients
A Phase 2, Randomized, Open-Label, Parallel Group, Multi-Center Study to Assess the Safety and Efficacy of Alefacept in de Novo Kidney Transplant Recipients
Aperçu de l'étude
Statut
Les conditions
Description détaillée
Type d'étude
Inscription (Réel)
Phase
- Phase 2
Contacts et emplacements
Lieux d'étude
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California
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Loma Linda, California, États-Unis, 92354
- Loma Linda University Medical Center
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Los Angeles, California, États-Unis, 90033
- University of Southern California - University Hospital
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Los Angeles, California, États-Unis, 90057
- St. Vincent/National Institute of Transplantation
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Sacramento, California, États-Unis, 95817
- UC Davis Medical Center
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San Diego, California, États-Unis, 92103
- UCSD
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San Diego, California, États-Unis, 92123
- California Institute of Renal Research/Sharp Memorial Hospital
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San Francisco, California, États-Unis, 94143
- University of California - San Francisco
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Colorado
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Aurora, Colorado, États-Unis, 80045
- University of Colorado Health Science Center
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Florida
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Gainesville, Florida, États-Unis, 32610
- University of Florida, Shands Hospital, Gainesville
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Jacksonville, Florida, États-Unis, 32224
- Mayo Clinic - Jacksonville
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Georgia
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Augusta, Georgia, États-Unis, 30921
- Medical College of Georgia, Augusta
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Illinois
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Chicago, Illinois, États-Unis, 60612
- University of Illinois at Chicago
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Chicago, Illinois, États-Unis, 60637
- University of Chicago Medical Center
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Chicago, Illinois, États-Unis, 60612
- Rush - Presbyterian - St. Lukes Medical Center
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Kentucky
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Lexington, Kentucky, États-Unis, 40536
- University of Kentucky
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Maryland
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Baltimore, Maryland, États-Unis, 21201
- University of Maryland Center
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Massachusetts
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Boston, Massachusetts, États-Unis, 02115
- Brigham and Women's Hospital
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Boston, Massachusetts, États-Unis, 02111
- Tufts Medical Center
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Michigan
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Ann Arbor, Michigan, États-Unis, 48109
- University of Michigan
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New Jersey
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Livingston, New Jersey, États-Unis, 07039
- St. Barnabas Medical Center
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New York
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Buffalo, New York, États-Unis, 14203
- Buffalo General Hospital
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New York, New York, États-Unis, 10029
- Mt. Sinai School of Medicine
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New York, New York, États-Unis, 10065
- New York Presbyterian Hospital - Cornell
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Valhalla, New York, États-Unis, 10595
- Westchester Medical Center
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North Carolina
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Chapel Hill, North Carolina, États-Unis, 27599
- University of North Carolina
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Durham, North Carolina, États-Unis, 27710
- Duke University Medical Center
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Ohio
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Cleveland, Ohio, États-Unis, 44106
- University Hospital of Cleveland
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Oregon
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Portland, Oregon, États-Unis, 97239
- Oregon Health & Science University
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Portland, Oregon, États-Unis, 97210
- Legacy Transplant Services
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Pennsylvania
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Harrisburg, Pennsylvania, États-Unis, 17101
- Pinnacle Health at Harrisburg
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Philadelphia, Pennsylvania, États-Unis, 19104
- University of Pennsylvania
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Tennessee
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Memphis, Tennessee, États-Unis, 38104
- Methodist University Hospital - Memphis
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Texas
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Dallas, Texas, États-Unis, 75246
- Baylor University Medical Center
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Houston, Texas, États-Unis, 77030
- Methodist Hospital Research Institute of Houston
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Utah
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Salt Lake City, Utah, États-Unis, 84132
- University of Utah Medical Center
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Virginia
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Richmond, Virginia, États-Unis, 23298
- Virginia Commonwealth University School of Medicine
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Washington
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Seattle, Washington, États-Unis, 98195
- University of Washington Medical Center
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Wisconsin
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Madison, Wisconsin, États-Unis, 53792
- University of Wisconsin Hospital
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Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Subject is anticipated to receive first oral dose of tacrolimus within 48 hours of transplant procedure
- Subject is a recipient of a de novo kidney transplant
- Subject is a recipient of a kidney from a non-human leukocyte antigen (HLA) identical related living donor, a non-related living donor, or a deceased donor
Exclusion Criteria:
- Subject has a screening (pre-operative)estimated cluster of differentiation (CD) 4+ T-cell count of < 250 cells/µL
- Subject will receive a kidney with an anticipated cold ischemia time (CIT) of > 30 hours
- Recipient has a positive T or B-cell cross match by investigational site's standard method of determination
Subject will receive a kidney from a 50-65 year old deceased donor with one of the following:
- History of hypertension and a terminal serum creatinine > 1.5 mg/dL
- Cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
- History of hypertension and cerebrovascular accident as cause of death and a terminal serum creatinine > 1.5 mg/dL
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
---|---|
Comparateur actif: Tacrolimus/MMF/Basiliximab
Participants received tacrolimus at a starting dose of 0.20 mg/kg/day, mycophenolate mofetil (MMF) 750 or 1000 mg twice daily (BID), basiliximab administered as a 20 mg bolus injection 2 hours prior to transplantation on Day 0 and a 20 mg bolus injection on Day 3 and tapered corticosteroids for 6 months.
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The initial dose of tacrolimus was administered orally within 48 hours post-transplant.
Subsequent doses were to be adjusted to achieve target whole blood trough concentrations.
Autres noms:
Administered as a 20 mg bolus injection within 2 hours prior to transplantation and a 20 mg bolus injection on Day 3.
Autres noms:
Administered at 750 mg twice per day orally or intravenously for patients enrolled under Amendment 6 or earlier and at 1000 mg twice per day orally or intravenously for patients enrolled under Amendment 7. The dose of MMF could be adjusted based on clinical symptoms.
Autres noms:
Corticosteroids were administered as a 500 to 1000 mg intravenous bolus on Day 0 and a 125 to 250 mg methylprednisone (or equivalent oral/intravenous corticosteroid dose) on Day 1. Oral prednisone was to be tapered per protocol.
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Expérimental: Alefacept QW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg intravenous (IV) bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly (QW) for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID and tapered corticosteroids for 6 months.
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The initial dose of tacrolimus was administered orally within 48 hours post-transplant.
Subsequent doses were to be adjusted to achieve target whole blood trough concentrations.
Autres noms:
Administered at 750 mg twice per day orally or intravenously for patients enrolled under Amendment 6 or earlier and at 1000 mg twice per day orally or intravenously for patients enrolled under Amendment 7. The dose of MMF could be adjusted based on clinical symptoms.
Autres noms:
Corticosteroids were administered as a 500 to 1000 mg intravenous bolus on Day 0 and a 125 to 250 mg methylprednisone (or equivalent oral/intravenous corticosteroid dose) on Day 1. Oral prednisone was to be tapered per protocol.
Administered as a 7.5 mg intravenous bolus on day 0 (intraoperatively, prior to kidney revascularization) and Day 3; subsequently administered subcutaneously either weekly or every 2 weeks.
Autres noms:
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Expérimental: Alefacept QW/Tacrolimus
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 15 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.20 mg/kg/day, and tapered corticosteroids for 6 months.
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The initial dose of tacrolimus was administered orally within 48 hours post-transplant.
Subsequent doses were to be adjusted to achieve target whole blood trough concentrations.
Autres noms:
Corticosteroids were administered as a 500 to 1000 mg intravenous bolus on Day 0 and a 125 to 250 mg methylprednisone (or equivalent oral/intravenous corticosteroid dose) on Day 1. Oral prednisone was to be tapered per protocol.
Administered as a 7.5 mg intravenous bolus on day 0 (intraoperatively, prior to kidney revascularization) and Day 3; subsequently administered subcutaneously either weekly or every 2 weeks.
Autres noms:
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Expérimental: Alefacept QOW/Tacrolimus/MMF
Participants received alefacept administered as a 7.5 mg IV bolus on Days 0 and 3; 30 mg subcutaneously on Day 7 then weekly for 12 weeks, then 15 mg subcutaneously monthly until the end of month 6, in addition to tacrolimus at a starting dose of 0.10 mg/kg/day, MMF 750 or 1000 mg BID, and tapered corticosteroids for 6 months.
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The initial dose of tacrolimus was administered orally within 48 hours post-transplant.
Subsequent doses were to be adjusted to achieve target whole blood trough concentrations.
Autres noms:
Administered at 750 mg twice per day orally or intravenously for patients enrolled under Amendment 6 or earlier and at 1000 mg twice per day orally or intravenously for patients enrolled under Amendment 7. The dose of MMF could be adjusted based on clinical symptoms.
Autres noms:
Corticosteroids were administered as a 500 to 1000 mg intravenous bolus on Day 0 and a 125 to 250 mg methylprednisone (or equivalent oral/intravenous corticosteroid dose) on Day 1. Oral prednisone was to be tapered per protocol.
Administered as a 7.5 mg intravenous bolus on day 0 (intraoperatively, prior to kidney revascularization) and Day 3; subsequently administered subcutaneously either weekly or every 2 weeks.
Autres noms:
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Percentage of Participants With Biopsy-confirmed Acute Rejection (BCAR) at Month 6 Assessed by Local Review
Délai: 6 months
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Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Day 182 was used for the analyses at 6 months. Lost to follow-up or patients with missing outcomes were censored at their last follow up visit. |
6 months
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
---|---|---|
Patient Survival at Month 6 and Month 12
Délai: 6 months and 12 months
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Patient survival is any participant who is known to be alive 6 months and 12 months after the skin closure date. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
6 months and 12 months
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Graft Survival at Month 6 and Month 12
Délai: 6 months and 12 months
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Graft survival was defined as any participant who was known to have a functioning graft (i.e., not graft loss) at 6 months and 12 months after the skin closure date. Graft loss was defined as patient death, retransplant, permanent return to dialysis (dialysis greater than 30 days) or transplant nephrectomy. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
6 months and 12 months
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Percentage of Participants With BCAR at Month 12 Assessed by Local Review
Délai: 12 months
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Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Day 365 was used for the analyses at 12 months. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
12 months
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Percentage of Participants With BCAR at Month 6 and 12 Assessed by Central Review
Délai: 6 months and 12 months
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Rejection episodes were confirmed by biopsy by a central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies (T-cell and/or antibody mediated) of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
6 months and 12 months
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Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Local Review
Délai: 6 months and 12 months
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Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
6 months and 12 months
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Percentage of Participants With T-cell Mediated BCAR at Month 6 and 12 Assessed by Central Review
Délai: 6 months and 12 months
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Rejection episodes were confirmed by biopsy by the central reviewer. Biopsies were graded according to the 2005 Banff criteria. All biopsies of grade 1 or higher were considered a BCAR. The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively. Lost to follow-up or participants with missing outcomes were censored at their last follow up visit. |
6 months and 12 months
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Change From Week 4 in Glomerular Filtration Rate Estimated by the MDRD Method at Month 6 and Month 12
Délai: Week 4, Month 6 and Month 12
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The glomerular filtration rate (GFR) was calculated using the Modification of Diet in Renal Disease (MDRD) method.
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Week 4, Month 6 and Month 12
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Change From Week 4 in GFR by Iothalamate Clearance at Month 6
Délai: Week 4 and Month 6
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The glomerular filtration rate was measured directly using iothalamate clearance.
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Week 4 and Month 6
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Change From Week 4 in Serum Creatinine at Month 6 and 12
Délai: Week 4 and Month 6 and 12
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Week 4 and Month 6 and 12
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Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Local Review
Délai: 6 months and 12 months
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Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to local review, or lost to follow-up.
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6 months and 12 months
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Percentage of Participants With Efficacy Failure at 6 and 12 Months Assessed by Central Review
Délai: 6 months and 12 months
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Efficacy failure is defined as death, graft failure (permanent return to dialysis [>30 days] or retransplant), BCAR according to central review, or lost to follow-up.
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6 months and 12 months
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Time to First BCAR Assessed by Local Review
Délai: 12 months
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The time to first BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1.
Only participants with a BCAR are included in the analysis.
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12 months
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Time to First BCAR Assessed by Central Review
Délai: 12 months
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The time to first BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1.
Only participants with a BCAR are included in the analysis.
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12 months
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Time to First T-cell Mediated BCAR Assessed by Local Review
Délai: 12 months
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The time to first T-cell mediated BCAR (local review) was calculated as the first biopsy date in which the local reviewer confirmed an acute rejection minus the date of skin closure +1.
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12 months
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Time to First T-cell Mediated BCAR Assessed by Central Review
Délai: 12 months
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The time to first T-cell mediated BCAR (central review) was calculated as the first biopsy date in which the central reviewer confirmed an acute rejection minus the date of skin closure +1.
Only participants with a T-cell mediated BCAR are included in the analysis.
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12 months
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Maximum Grade of T-cell Mediated Rejection Assessed by Local Review
Délai: 6 months and 12 months
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The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis. Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation. |
6 months and 12 months
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Maximum Grade of T-cell Mediated Rejection as Assessed by Central Review
Délai: 6 months and 12 months
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The grade of acute T-cell mediated rejection was classified as IA, IB, IIA, IIB and III according to Banff 2005 criteria. If a patient had more than 1 T-cell mediated rejection, the episode with the most severe grade was used in the analysis. Grade IA: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of moderate tubulitis; Grade IB: Cases with significant interstitial infiltration (> 25% of parenchyma affected) and foci of severe tubulitis; Grade IIA: Cases with mild to moderate intimal arteritis; Grade IIB: Cases with severe intimal arteritis comprising >25% of the luminal area; Grade III: Cases with "transmural" arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation. |
6 months and 12 months
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Percentage of Participants With Clinically Treated Acute Rejection at Month 6 and Month 12
Délai: 6 months and 12 months
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Patients who received immunosuppressive medications for the treatment of suspected or BCAR were considered to have a clinically-treated acute rejection.
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6 months and 12 months
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Percentage of Participants With Anti-lymphocyte-treated Rejection at Months 6 and 12
Délai: 6 months and 12 months
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Participants with histologically proved Banff Grade II or III rejection could receive anti-rejection therapy with anti-lymphocyte antibodies per institutional protocol. The use of anti-lymphocyte antibody therapy at any time during a suspected or proven rejection episode for the treatment of acute rejection was considered an event. |
6 months and 12 months
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Percentage of Participants With Multiple Rejection Episodes at Months 6 and 12
Délai: 6 months and 12 months
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All participants were evaluated for the incidence of multiple rejection episodes (clinically treated and/or BCAR as assessed by the local reviewer) through 6 months and 12 months.
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6 months and 12 months
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Percentage of Participants With Treatment Failure at Month 6 and 12
Délai: 6 months and 12 months
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Treatment failure was defined as death, graft loss, BCAR (local review), lost to follow-up or early discontinuation of treatment regimen.
The Kaplan-Meier estimates at Days 182 and 365 were used for the analyses at 6 months and 12 months respectively.
Lost to follow-up or participants with missing outcomes were censored at their last follow up visit.
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6 months and 12 months
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Gastrointestinal Quality of Life Index Score Over Time
Délai: Months 1, 3, 6, and 12
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The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Quality of Life Index (GIQLI) symptom severity score.
The GIQLI is a 36-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past 2 weeks on a scale from 0 (all of the time) to 4 (never).
Possible overall scores ranged from 0 to 4, with higher scores indicating a better quality of life according to the different symptomatic criteria.
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Months 1, 3, 6, and 12
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Gastrointestinal Symptom Rating Scale Scores Over Time
Délai: Months 1, 3, 6, and 12
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The impact of gastrointestinal (GI) symptoms on health-related quality of life was assessed using the Gastrointestinal Symptom Rating Scale Scores (GSRS).
The GSRS a 15-item self-administered questionnaire that assesses the impact of gastrointestinal symptoms during the past week on a scale from 1 (no discomfort at all) to 7 (very severe discomfort).
Possible overall scores range from 1 to 7, with lower scores indicating a better quality of life with respect to gastrointestinal symptoms.
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Months 1, 3, 6, and 12
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Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: Principal Investigator, University of Michigan
Publications et liens utiles
Liens utiles
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude
Achèvement primaire (Réel)
Achèvement de l'étude (Réel)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Estimation)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Estimation)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Mots clés
Termes MeSH pertinents supplémentaires
- Effets physiologiques des médicaments
- Mécanismes moléculaires de l'action pharmacologique
- Agents anti-infectieux
- Inhibiteurs d'enzymes
- Agents antinéoplasiques
- Agents immunosuppresseurs
- Facteurs immunologiques
- Agents dermatologiques
- Agents antibactériens
- Antibiotiques, Antinéoplasiques
- Agents antituberculeux
- Antibiotiques, Antituberculeux
- Inhibiteurs de la calcineurine
- Tacrolimus
- Acide mycophénolique
- Basiliximab
- Aléfacept
Autres numéros d'identification d'étude
- 0485-CL-U201
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