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| Name | Class |
|---|---|
| Astellas Pharma Inc | INDUSTRY |
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This study was designed to determine which maintenance immunosuppressive agent, rapamycin or mycophenalate mofetil, resulted in better outcome in patients with type 1 diabetes and renal failure, who presented for a kidney-pancreas transplant.
This is a randomized, prospective single center study evaluating the two maintenance drugs above.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tacrolimus plus MMF plus Steroids | Active Comparator | Patients randomized to this arm were scheduled to receive maintenance therapy consisting of Tacrolimus, Mycophenolate Mofetil (MMF), and Steroids. Patients in both treatment arms received dual induction therapy consisting of Rabbit Anti-thymocyte Globulin (Thymoglobulin) plus Daclizumab. |
|
| Tacrolimus plus Rapamycin plus Steroids | Experimental | Patients randomized to this arm were scheduled to receive maintenance therapy consisting of Tacrolimus, Rapamycin (Sirolimus), and Steroids. Patients in both treatment arms received dual induction therapy consisting of Rabbit Anti-thymocyte Globulin (Thymoglobulin) plus Daclizumab. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Rapamycin | Drug | Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. |
| Measure | Description | Time Frame |
|---|---|---|
| Event-Specific Survival Comparisons | Freedom from biopsy-proven acute rejection of the kidney allograft; Freedom from biopsy-proven acute rejection of the pancreas allograft; Death-censored kidney graft survival; Death-censored pancreas graft survival; Death-uncensored graft (kidney and pancreas) survival; and Patient survival. | over 1-10 years post-transplant |
| Measure | Description | Time Frame |
|---|---|---|
| Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant. | Comparisons of renal function (eGFR, measured in mL/min/1.73 m^2) at 12, 36, and 60 months post-transplant. | at 1-5 years post-transplant |
| Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| George W Burke, MD | University of Miami | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Miami, Miller School of Medicine | Miami | Florida | 33136 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 12176628 | Result | Burke GW 3rd, Ciancio G, Figueiro J, Olson L, Gomez C, Rosen A, Suzart K, Miller J. Steroid-resistant acute rejection following SPK: importance of maintaining therapeutic dosing in a triple-drug regimen. Transplant Proc. 2002 Aug;34(5):1918-9. doi: 10.1016/s0041-1345(02)03122-6. No abstract available. | |
| 12176626 | Result |
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A randomized block design was implemented for the randomization scheme using Proc Plan in SAS. Patients were randomly assigned (allocation ratio of 1:1) to the two treatment arms in blocks of 4 and 6 patients (block sizes were also chosen randomly), ensuring a balance of patients across treatment arms after each block of patients was randomized.
From September 1, 2000 through December 15, 2009, 170 consecutive patients with type 1 diabetes and ESRD were randomized to receive either Rapamycin (N=84) or MMF (N=86) immediately prior to transplant. Post-transplant clinical follow-up of patients continued through January 15, 2011.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tacrolimus Plus MMF Plus Steroids | This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation. Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day |
| FG001 | Tacrolimus Plus Rapamycin Plus Steroids | Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation. Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels: 10-15ng/ml) Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Allocation and Intent to Treat Analysis |
| |||||||||||||
| Follow-up |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Tacrolimus Plus MMF Plus Steroids | This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation. Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day |
| BG001 | Tacrolimus Plus Rapamycin Plus Steroids |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Event-Specific Survival Comparisons | Freedom from biopsy-proven acute rejection of the kidney allograft; Freedom from biopsy-proven acute rejection of the pancreas allograft; Death-censored kidney graft survival; Death-censored pancreas graft survival; Death-uncensored graft (kidney and pancreas) survival; and Patient survival. | Posted | Count of Participants | Participants | over 1-10 years post-transplant |
|
during the first year post-transplant
Serious Adverse Events were defined as: 1) the occurrence of any infection that required hospitalization, and 2) a major cardiovascular event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tacrolimus Plus MMF Plus Steroids | This group of kidney-pancreas recipients was randomized to receive mycophenolate mofetil and tacrolimus after transplantation. Tacrolimus and mycophenolate mofetil: MMF 1 gm BID beginning 1st day postoperative day |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Infection | Infections and infestations | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| New Onset Diabetes Mellitus Type 2 after Transplant (NODAT) | Endocrine disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. George W. Burke, III | University of Miami | 305-355-5111 | gburke@med.miami.edu |
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| ID | Term |
|---|---|
| D003922 | Diabetes Mellitus, Type 1 |
| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
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| ID | Term |
|---|---|
| D020123 | Sirolimus |
| D009173 | Mycophenolic Acid |
| D016559 | Tacrolimus |
| D013256 | Steroids |
| D000305 | Adrenal Cortex Hormones |
| ID | Term |
|---|---|
| D018942 | Macrolides |
| D007783 | Lactones |
| D009930 | Organic Chemicals |
| D002208 | Caproates |
| D000144 |
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|
| Mycophenolate Mofetil | Drug | MMF 1 gm BID beginning 1st day postoperative day |
|
|
| Tacrolimus | Drug | Part of standard maintenance. |
|
|
| Steroids | Drug | Part of standard maintenance |
|
|
Comparisons of pancreas function (C-peptide in ng/mL) at 12, 36, and 60 months post-transplant. |
| at 1-5 years post-transplant |
| Burke G 3rd, Ciancio G, Figueiro J, Olson L, Gomez C, Rosen A, Suzart K, Miller J. Can acute rejection be prevented in SPK transplantation? Transplant Proc. 2002 Aug;34(5):1913-4. doi: 10.1016/s0041-1345(02)03149-4. No abstract available. |
| 15233820 | Result | Burke GW 3rd, Ciancio G, Figueiro J, Buigas R, Olson L, Roth D, Kupin W, Miller J. Hypercoagulable state associated with kidney-pancreas transplantation. Thromboelastogram-directed anti-coagulation and implications for future therapy. Clin Transplant. 2004 Aug;18(4):423-8. doi: 10.1111/j.1399-0012.2004.00183.x. |
| 22946986 | Result | Ciancio G, Sageshima J, Chen L, Gaynor JJ, Hanson L, Tueros L, Montenora-Velarde E, Gomez C, Kupin W, Guerra G, Mattiazzi A, Fornoni A, Pugliese A, Roth D, Wolf M, Burke GW 3rd. Advantage of rapamycin over mycophenolate mofetil when used with tacrolimus for simultaneous pancreas kidney transplants: randomized, single-center trial at 10 years. Am J Transplant. 2012 Dec;12(12):3363-76. doi: 10.1111/j.1600-6143.2012.04235.x. Epub 2012 Sep 4. |
| NOT COMPLETED |
|
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation. Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels: 10-15ng/ml) Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation.
Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels:
10-15ng/ml)
Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day.
|
|
|
| Secondary | Overall Kidney Transplant Function at 12, 36, and 60 Months Post-transplant. | Comparisons of renal function (eGFR, measured in mL/min/1.73 m^2) at 12, 36, and 60 months post-transplant. | Number analyzed here includes all patients alive with a functioning graft that had an available measurement taken at that time | Posted | Mean | Standard Error | mL/min/1.73m^2 | at 1-5 years post-transplant |
|
|
|
|
| Secondary | Overall Pancreas Transplant Function at 12, 36, and 60 Months Post-transplant. | Comparisons of pancreas function (C-peptide in ng/mL) at 12, 36, and 60 months post-transplant. | Number analyzed here includes all patients alive with a functioning graft that had an available measurement taken at that time | Posted | Mean | Standard Error | ng/mL | at 1-5 years post-transplant |
|
|
|
|
| 16 |
| 86 |
| 40 |
| 86 |
| 3 |
| 86 |
| EG001 | Tacrolimus Plus Rapamycin Plus Steroids | Patients randomized to this arm received Sirolimus, after kidney-pancreas transplantation. Rapamycin: Rapamycin was initiated on day 1 postoperatively, 4mg/day;levels were maintained 5-8ng/ml. Those patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. Rapamune and Tacrolimus: Sirolimus 2 mg/day beginning 1st postoperative day (trough target levels: 10-15ng/ml) Mycophenolate Mofetil: Patients randomized to receive mycophenolate mofetil were given 1gm twice/day starting on the first post-operative day. | 15 | 84 | 38 | 84 | 5 | 84 |
| Major Cardiovascular Event | Vascular disorders | Non-systematic Assessment |
|
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| D004700 | Endocrine System Diseases |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| Acids, Acyclic |
| D002264 | Carboxylic Acids |
| D005227 | Fatty Acids |
| D008055 | Lipids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| Mean eGFR at 36 months |
|
|
| Mean eGFR at 60 months |
|
|
| 0.71 |
| Superiority |
| Comparison of Mean eGFR at 60 Months Post-Transplant (t-test). | t-test, 2 sided | 0.33 | Superiority |
| Mean Log {C-peptide at 36 months} |
|
|
| Mean Log {C-peptide at 60 months} |
|
|
| 0.97 |
| Superiority |
| Comparison of Mean Log {C-Peptide Level} at 60 Months Post-Transplant (t-test). | t-test, 2 sided | 0.75 | Superiority |