Comparative Study of Modified Release (MR) Tacrolimus/Mycophenolate Mofetil (MMF) in de Novo Kidney Transplant Recipients
A Phase III, Randomized, Open-Label, Comparative, Multi-Center Study to Assess the Safety and Efficacy of Prograf (Tacrolimus)/MMF, Modified Release (MR) Tacrolimus/MMF and Neoral (Cyclosporine)/MMF in de Novo Kidney Transplant Recipients
연구 개요
상태
정황
상세 설명
This was a 3 arm randomized, open-label, comparative, multi-center study in de novo kidney transplant recipients at 60 centers in the U.S., Canada and Brazil.
The study consisted of a 1-year post-transplant efficacy and safety study with a clinical continuation phase of a minimum of 2 years or until commercial availability of tacrolimus modified release, unless the Data Safety Monitoring Board or sponsor specified otherwise.
연구 유형
등록 (실제)
단계
- 3단계
연락처 및 위치
연구 장소
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Alabama
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Birmingham, Alabama, 미국, 35294
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Mobile, Alabama, 미국, 36617
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California
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Loma Linda, California, 미국, 92354
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Los Angeles, California, 미국, 90033
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Los Angeles, California, 미국, 90057
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Los Angeles, California, 미국, 90058
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Los Angeles, California, 미국, 90095-7306
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Palo Alto, California, 미국, 94304
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San Diego, California, 미국, 92103
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San Diego, California, 미국, 92123
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San Francisco, California, 미국, 94115
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Colorado
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Denver, Colorado, 미국, 80262
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District of Columbia
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Washington, District of Columbia, 미국, 20010
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Florida
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Gainesville, Florida, 미국, 32610-0224
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Jacksonville, Florida, 미국, 32216
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Georgia
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Augusta, Georgia, 미국, 30912
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Illinois
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Chicago, Illinois, 미국, 60637
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Chicago, Illinois, 미국, 60612
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Indiana
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Indianapolis, Indiana, 미국, 46202
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Kentucky
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Lexington, Kentucky, 미국, 40536
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Louisiana
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New Orleans, Louisiana, 미국, 70112
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New Orleans, Louisiana, 미국, 70121
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Massachusetts
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Boston, Massachusetts, 미국, 02214
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Michigan
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Ann Arbor, Michigan, 미국, 48109-0364
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Detroit, Michigan, 미국, 48202
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New Jersey
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Livingston, New Jersey, 미국, 07039
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New Brunswick, New Jersey, 미국, 08901
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New York
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Albany, New York, 미국, 12208
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Buffalo, New York, 미국, 14203
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New York, New York, 미국, 10029
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Valhalla, New York, 미국, 10595
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North Carolina
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Chapel Hill, North Carolina, 미국, 27599-7211
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Durham, North Carolina, 미국, 27710
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Ohio
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Cincinnati, Ohio, 미국, 45267
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Oregon
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Portland, Oregon, 미국, 97210
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Portland, Oregon, 미국, 97239-2940
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Pennsylvania
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Harrisburg, Pennsylvania, 미국, 17104
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Philadelphia, Pennsylvania, 미국, 19104
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Philadelphia, Pennsylvania, 미국, 19107
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Tennessee
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Nashville, Tennessee, 미국, 37212-4750
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Texas
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Dallas, Texas, 미국, 75246
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Dallas, Texas, 미국, 75235
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Houston, Texas, 미국, 77030
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San Antonio, Texas, 미국, 78229-3900
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Utah
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Salt Lake City, Utah, 미국, 84132
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Virginia
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Fairfax, Virginia, 미국, 22031
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Wisconsin
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Madison, Wisconsin, 미국, 53792-7375
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Milwaukee, Wisconsin, 미국, 53226
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Porto Alegre, 브라질, 90240-520
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Rio de Janeiro, 브라질, 21041-003
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Sao Paulo, 브라질, 04038-002
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Sao Paulo, 브라질, 04013-043
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Sao Paulo, 브라질, 05465-040
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Alberta
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Edmonton, Alberta, 캐나다
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British Columbia
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Vancouver, British Columbia, 캐나다
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Ontario
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Toronto, Ontario, 캐나다
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Quebec
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Montreal, Quebec, 캐나다
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참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
설명
Inclusion Criteria:
- Recipient of a primary or retransplanted non-human leukocyte antigen (HLA)-identical living or non-HLA-identical cadaveric kidney transplant
- Age greater or equal to 12 years
Exclusion Criteria:
- Recipient or donor is known seropositive for human immunodeficiency virus (HIV)
- Has current malignancy or history of malignancy
- Has significant liver disease
- Has uncontrolled concomitant infection or any other unstable medical condition
- Is receiving everolimus or enteric coated mycophenolic acid at any time during the study
- Received kidney with a cold ischemia time of equal or more than 36 hours
- Received kidney transplant from a cadaveric donor equal or more than 60 years of age
- Received intravenous immunoglobulin (IVIG) therapy prior to randomization
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
- 주 목적: 치료
- 할당: 무작위
- 중재 모델: 병렬 할당
- 마스킹: 없음(오픈 라벨)
무기와 개입
참가자 그룹 / 팔 |
개입 / 치료 |
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실험적: Tacrolimus
Participants received a first dose of tacrolimus between 0.075 and 0.10 mg/kg twice daily, orally prior to or within 48 hours of the completion of the transplant procedure, and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events.
Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
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The target range for whole blood tacrolimus trough concentrations was the recommended trough concentration range for Prograf: 7 to 16 ng/mL for days 0 through 90 and 5 to 15 ng/mL thereafter.
다른 이름들:
Oral
다른 이름들:
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활성 비교기: Tacrolimus Modified Release
Participants received a first dose of tacrolimus modified release between 0.15 and 0.20 mg/kg/day, given as a single oral dose in the morning, prior to or within 48 hours following the completion of the transplant procedure, and subsequently as once daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events.
Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
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Oral
다른 이름들:
The target range for whole blood tacrolimus trough concentrations was 7 to 16 ng/mL for days 0 through 90, and 5 to 15 ng/mL thereafter.
다른 이름들:
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활성 비교기: Cyclosporine
Participants received a first dose of cyclosporine between 4 to 5 mg/kg orally prior to or within 48 hours following the completion of the transplant procedure and subsequently as twice daily oral doses adjusted based on clinical evidence of efficacy, blood concentrations of tacrolimus and adverse events.
Participants also received 1.0 g mycophenolate mofetil orally twice daily throughout the study.
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Oral
다른 이름들:
The target range for whole blood cyclosporine trough concentrations was 125 to 400 ng/mL for days 0 through 90, and 100 to 300 ng/mL thereafter.
다른 이름들:
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연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Percentage of Participants With Efficacy Failure
기간: one year
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Efficacy failure is defined as any participant who died, experienced a graft failure (permanent return to dialysis [> 30 days] or retransplant), had a biopsy-confirmed (Banff Grade ≥ I) acute rejection (BCAR), or was lost to follow-up. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year
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2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
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Patient Survival at One Year
기간: One year
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Patient survival is defined as any participant who is known to be alive one year after the skin closure date.
Participants who died or whose outcome was unknown at one year were considered to be non-survivors.
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One year
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Graft Survival at One Year
기간: One year
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Graft survival defined as any participant who did not meet the criteria for graft loss, where graft loss is defined as any re-transplant, permanent return to dialysis (> 30 days), patient death, or participant whose outcome at one year was unknown. Participants were only counted once regardless of how many criteria were met. |
One year
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Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months
기간: Six 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 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade ≥ I. |
Six months and 12 months
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Time to First Biopsy-confirmed Acute Rejection Episode
기간: one year
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Time to first biopsy-confirmed acute rejection episode defined as the number of days from skin closure (Day 0) to the date of biopsy. Rejection episodes were confirmed by biopsy by the clinical site pathologist and graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. Acute rejection is defined as a grade ≥ I. |
one year
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Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection
기간: one year
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Rejection episodes were confirmed by biopsy by the clinical site pathologist. Participants with histologically-proven Banff Grade II or III rejection or participants with steroid-resistant rejection were treated with anti-lymphocyte antibody treatment according to institutional practice. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade I: Significant interstitial infiltration and foci of moderate to severe tubulitis; Grade II: Mild to severe intimal arteritis Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year
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Severity of Acute Rejection
기간: one year
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Rejection episodes were confirmed by biopsy by the clinical site pathologist. Biopsies were graded according to the 1997 Banff criteria: Borderline: No intimal arteritis present but foci of mild tubulitis; Grade IA: Significant interstitial infiltration and foci of moderate tubulitis; Grade IB: Significant interstitial infiltration and foci of severe tubulitis; Grade IIA: Mild to moderate intimal arteritis in at least 1 arterial cross section Grade IIB: Severe intimal arteritis comprising >25% of the luminal area lost in at least 1 arterial cross section; Grade III: Transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic infiltrate in vessel. |
one year
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Number of Participants Experiencing Multiple Rejection Episodes
기간: one year
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This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.
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one year
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Number of Participants With Clinically Treated Acute Rejection Episodes
기간: one year
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A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.
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one year
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Number of Participants With Treatment Failure
기간: one year
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Treatment failure was defined as the discontinuation of randomized study drug for any reason.
Participants who met the definition of treatment failure were to be followed throughout the 12-month treatment period.
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one year
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Number of Participants Who Crossed Over Due to Treatment Failure
기간: one year
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Participants were allowed to cross over to an alternative primary immunosuppressive regimen (either to the tacrolimus or cyclosporine treatment arms) to address an adverse event which led to randomized study drug discontinuation or in the case of severe or refractory rejection.
Crossover to the modified release tacrolimus treatment arm was not permitted.
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one year
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Change From Month 1 in Serum Creatinine at Month 6 and Month 12
기간: Month 1, Month 6, and Month 12
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Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant.
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Month 1, Month 6, and Month 12
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Change From Month 1 in Creatinine Clearance at Month 6 and Month 12
기간: Month 1, Month 6, and Month 12
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Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula.
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Month 1, Month 6, and Month 12
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Kaplan-Meier Estimate of Patient Survival at the End of the Study
기간: End of study (maximum time on study was 1,941 days).
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Patient survival was defined as any participant who was alive at the end of the study.
Patient survival was censored at the time of last follow-up contact.
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End of study (maximum time on study was 1,941 days).
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Kaplan-Meier Estimate of Graft Survival at the End of the Study
기간: End of study (maximum time on study was 1,941 days).
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Graft survival was defined as any participant who did not meet the definition of graft loss, where graft loss was any retransplant or the permanent return to dialysis (more than 30 days) or patient death. Graft survival was censored at the time of last follow-up contact. |
End of study (maximum time on study was 1,941 days).
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공동 작업자 및 조사자
간행물 및 유용한 링크
연구 기록 날짜
연구 주요 날짜
연구 시작
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (추정)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
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