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Comparative Study of Modified Release (MR) Tacrolimus/Mycophenolate Mofetil (MMF) in de Novo Kidney Transplant Recipients

Sponsor
Astellas Pharma Inc (Industry)
Overall Status
Completed
CT.gov ID
NCT00064701
Collaborator
(none)
668
Enrollment
57
Locations
3
Arms
69
Duration (Months)
11.7
Patients Per Site
0.2
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the safety and efficacy of tacrolimus/mycophenolate mofetil (MMF), cyclosporine/MMF and tacrolimus modified release/MMF in de novo kidney transplant recipients.

Condition or Disease Intervention/Treatment Phase
  • Drug: Tacrolimus Modified Release (MR)
  • Drug: Tacrolimus
  • Drug: cyclosporine microemulsion
  • Drug: mycophenolate mofetil
 Phase 3

Detailed Description

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
668 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
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
Study Start Date :
Jun 1, 2003
Actual Primary Completion Date :
Mar 1, 2005
Actual Study Completion Date :
Mar 1, 2009

Arms and Interventions

Arm Intervention/Treatment
Experimental: 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.

Drug: Tacrolimus
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.
Other Names:
  • Prograf, FK506

    • Drug: mycophenolate mofetil
    Oral
    Other Names:
  • CellCept, MMF

    		•
    Active Comparator: 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.

    Drug: Tacrolimus Modified Release (MR)
    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.
    Other Names:
  • Advagraf, FK506, FKMR, MR4, Astagraf XL

    • Drug: mycophenolate mofetil
    Oral
    Other Names:
  • CellCept, MMF

    		•
    Active Comparator: 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.

    Drug: cyclosporine microemulsion
    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.
    Other Names:
  • Neoral, CsA

    • Drug: mycophenolate mofetil
    Oral
    Other Names:
  • CellCept, MMF

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Percentage of Participants With Efficacy Failure [one year]

      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.

    Secondary Outcome Measures

    1. Patient Survival at One Year [One year]

      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.

    2. Graft Survival at One Year [One year]

      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.

    3. Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months [Six months and 12 months]

      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.

    4. Time to First Biopsy-confirmed Acute Rejection Episode [one year]

      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.

    5. Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection [one year]

      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.

    6. Severity of Acute Rejection [one year]

      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.

    7. Number of Participants Experiencing Multiple Rejection Episodes [one year]

      This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.

    8. Number of Participants With Clinically Treated Acute Rejection Episodes [one year]

      A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.

    9. Number of Participants With Treatment Failure [one year]

      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.

    10. Number of Participants Who Crossed Over Due to Treatment Failure [one year]

      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.

    11. Change From Month 1 in Serum Creatinine at Month 6 and Month 12 [Month 1, Month 6, and Month 12]

      Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant.

    12. Change From Month 1 in Creatinine Clearance at Month 6 and Month 12 [Month 1, Month 6, and Month 12]

      Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula.

    13. Kaplan-Meier Estimate of Patient Survival at the End of the Study [End of study (maximum time on study was 1,941 days).]

      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.

    14. Kaplan-Meier Estimate of Graft Survival at the End of the Study [End of study (maximum time on study was 1,941 days).]

      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.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    12 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35294
    2 Mobile Alabama United States 36617
    3 Loma Linda California United States 92354
    4 Los Angeles California United States 90033
    5 Los Angeles California United States 90057
    6 Los Angeles California United States 90058
    7 Los Angeles California United States 90095-7306
    8 Palo Alto California United States 94304
    9 San Diego California United States 92103
    10 San Diego California United States 92123
    11 San Francisco California United States 94115
    12 Denver Colorado United States 80262
    13 Washington District of Columbia United States 20010
    14 Gainesville Florida United States 32610-0224
    15 Jacksonville Florida United States 32216
    16 Augusta Georgia United States 30912
    17 Chicago Illinois United States 60612
    18 Chicago Illinois United States 60637
    19 Indianapolis Indiana United States 46202
    20 Lexington Kentucky United States 40536
    21 New Orleans Louisiana United States 70112
    22 New Orleans Louisiana United States 70121
    23 Boston Massachusetts United States 02214
    24 Ann Arbor Michigan United States 48109-0364
    25 Detroit Michigan United States 48202
    26 Livingston New Jersey United States 07039
    27 New Brunswick New Jersey United States 08901
    28 Albany New York United States 12208
    29 Buffalo New York United States 14203
    30 New York New York United States 10029
    31 Valhalla New York United States 10595
    32 Chapel Hill North Carolina United States 27599-7211
    33 Durham North Carolina United States 27710
    34 Cincinnati Ohio United States 45267
    35 Portland Oregon United States 97210
    36 Portland Oregon United States 97239-2940
    37 Harrisburg Pennsylvania United States 17104
    38 Philadelphia Pennsylvania United States 19104
    39 Philadelphia Pennsylvania United States 19107
    40 Nashville Tennessee United States 37212-4750
    41 Dallas Texas United States 75235
    42 Dallas Texas United States 75246
    43 Houston Texas United States 77030
    44 San Antonio Texas United States 78229-3900
    45 Salt Lake City Utah United States 84132
    46 Fairfax Virginia United States 22031
    47 Madison Wisconsin United States 53792-7375
    48 Milwaukee Wisconsin United States 53226
    49 Porto Alegre Brazil 90240-520
    50 Rio de Janeiro Brazil 21041-003
    51 Sao Paulo Brazil 04013-043
    52 Sao Paulo Brazil 04038-002
    53 Sao Paulo Brazil 05465-040
    54 Edmonton Alberta Canada
    55 Vancouver British Columbia Canada
    56 Toronto Ontario Canada
    57 Montreal Quebec Canada

    Sponsors and Collaborators

    • Astellas Pharma Inc

    Investigators

    • Study Director: Use Central Contact, Astellas Pharma Global Development

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT00064701
    Other Study ID Numbers:
    • 02-0-158
    First Posted:
    Jul 14, 2003
    Last Update Posted:
    Dec 5, 2013
    Last Verified:
    Nov 1, 2013
    Keywords provided by Astellas Pharma Inc
    De Novo Kidney Transplant
    cyclosporine
    Prograf®
    mycophenolate mofetil
    tacrolimus
    Additional relevant MeSH terms:
    Cyclosporine
    Mycophenolic Acid
    Tacrolimus
    Cyclosporins

    Study Results

    Participant Flow

    Recruitment Details De novo kidney transplant recipients 12 years of age and older were randomized in a 1:1:1 ratio to 1 of 3 treatment arms.
    Pre-assignment Detail This study was a 1-year safety and efficacy study followed by a clinical continuation phase that continued until the sponsor discontinued the study in March 2009.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Period Title: One Year Post-transplant
    STARTED 219 226 223
    Received Study Drug 212 214 212
    COMPLETED 179 183 151
    NOT COMPLETED 40 43 72
    Period Title: One Year Post-transplant
    STARTED 179 182 151
    COMPLETED 9 4 11
    NOT COMPLETED 170 178 140

    Baseline Characteristics

    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine Total
    Arm/Group Description 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. 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. 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. Total of all reporting groups
    Overall Participants 212 214 212 638
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    48.62
    (12.855)
    47.84
    (12.995)
    47.63
    (12.953)
    48.03
    (12.921)
    Sex: Female, Male (Count of Participants)
    Female
    76
    35.8%
    76
    35.5%
    82
    38.7%
    234
    36.7%
    Male
    136
    64.2%
    138
    64.5%
    130
    61.3%
    404
    63.3%
    Race/Ethnicity, Customized (participants) [Number]
    White
    152
    71.7%
    160
    74.8%
    163
    76.9%
    475
    74.5%
    Black
    51
    24.1%
    41
    19.2%
    36
    17%
    128
    20.1%
    Asian
    5
    2.4%
    5
    2.3%
    8
    3.8%
    18
    2.8%
    Other
    4
    1.9%
    8
    3.7%
    5
    2.4%
    17
    2.7%
    Primary Diagnosis (participants) [Number]
    Nephrosclerosis/ Hypertensive Nephropathy
    54
    25.5%
    56
    26.2%
    43
    20.3%
    153
    24%
    Diabetic Nephropathy
    46
    21.7%
    38
    17.8%
    46
    21.7%
    130
    20.4%
    Glomerulonephritis
    44
    20.8%
    43
    20.1%
    43
    20.3%
    130
    20.4%
    Polycycstic Kidney Disease
    20
    9.4%
    26
    12.1%
    20
    9.4%
    66
    10.3%
    Tubular/ Interstitial Disease
    9
    4.2%
    5
    2.3%
    16
    7.5%
    30
    4.7%
    Systemic Vasculitis
    9
    4.2%
    10
    4.7%
    7
    3.3%
    26
    4.1%
    Congenital/ Hereditary Nephropathy
    7
    3.3%
    7
    3.3%
    13
    6.1%
    27
    4.2%
    Reflux
    1
    0.5%
    0
    0%
    1
    0.5%
    2
    0.3%
    Unknown
    17
    8%
    24
    11.2%
    17
    8%
    58
    9.1%
    Other
    5
    2.4%
    5
    2.3%
    6
    2.8%
    16
    2.5%
    Previous Transplant (participants) [Number]
    No
    205
    96.7%
    206
    96.3%
    203
    95.8%
    614
    96.2%
    Yes
    7
    3.3%
    8
    3.7%
    9
    4.2%
    24
    3.8%

    Outcome Measures

    1. Primary Outcome
    Title Percentage of Participants With Efficacy Failure
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set, defined as all randomized patients who received at least one dose of study drug.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [percentage of participants]
    15.1
    7.1%
    14.0
    6.5%
    17.0
    8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value -1.9
    Confidence Interval (2-Sided) 95.2%
    -8.9 to 5.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value -3.0
    Confidence Interval (2-Sided) 95.2%
    -9.9 to 4.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Patient Survival at One Year
    Description 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.
    Time Frame One year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [percentage of participants]
    93.9
    44.3%
    97.2
    45.4%
    97.2
    45.8%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value -3.3
    Confidence Interval (2-Sided) 95%
    -7.2 to 0.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -3.1 to 3.2
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Graft Survival at One Year
    Description 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.
    Time Frame One year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [percentage of participants]
    91.5
    43.2%
    95.3
    44.5%
    95.3
    45%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -8.5 to 0.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference
    Estimated Value 0.0
    Confidence Interval (2-Sided) 95%
    -4.0 to 4.1
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Percentage of Participants With Biopsy Confirmed Acute Rejection at 6 and 12 Months
    Description 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.
    Time Frame Six months and 12 months

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    At 6 Months
    3.8
    1.8%
    7.9
    3.7%
    11.8
    5.6%
    At 12 Months
    7.5
    3.5%
    10.3
    4.8%
    13.7
    6.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments Comparison of tacrolimus with cyclosporine at 6 months
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference at 6 Months
    Estimated Value -8.0
    Confidence Interval (2-Sided) 95%
    -13.1 to -3.0
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments Comparison of Tacrolimus Modified Release with Cyclosporine at 6 months
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference at 6 Months
    Estimated Value -3.8
    Confidence Interval (2-Sided) 95%
    -9.5 to 1.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 3
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments Comparison of tacrolimus with cyclosporine at 12 months
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference at 12 Months
    Estimated Value -6.1
    Confidence Interval (2-Sided) 95%
    -12.0 to -0.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 4
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments Comparison of Tacrolimus Modified Release with Cyclosporine at 12 months
    Type of Statistical Test Non-Inferiority or Equivalence
    Comments The non-inferiority margin for this study was pre-specified as 10%.
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Incidence Difference at 12 months
    Estimated Value -3.4
    Confidence Interval (2-Sided) 95%
    -9.6 to 2.8
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Time to First Biopsy-confirmed Acute Rejection Episode
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Median (Full Range) [days]
    156.00
    11.00
    52.00
    6. Secondary Outcome
    Title Number of Participants Requiring Anti-lymphocyte Antibody Therapy for Treatment of Rejection
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [participants]
    6
    2.8%
    8
    3.7%
    18
    8.5%
    7. Secondary Outcome
    Title Severity of Acute Rejection
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set with a biopsy-confirmed acute rejection episode during one year.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 16 22 29
    Grade I-A
    8
    3.8%
    11
    5.1%
    14
    6.6%
    Grade I-B
    4
    1.9%
    3
    1.4%
    6
    2.8%
    Grade II-A
    3
    1.4%
    6
    2.8%
    6
    2.8%
    Grade II-B
    1
    0.5%
    1
    0.5%
    1
    0.5%
    Grade III
    0
    0%
    1
    0.5%
    2
    0.9%
    8. Secondary Outcome
    Title Number of Participants Experiencing Multiple Rejection Episodes
    Description This analysis includes rejection episodes that were either confirmed by biopsy by the clinical site pathologist or were clinically treated.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [participants]
    2
    0.9%
    4
    1.9%
    8
    3.8%
    9. Secondary Outcome
    Title Number of Participants With Clinically Treated Acute Rejection Episodes
    Description A clinically treated acute rejection episode was any biopsy-confirmed or suspected rejection episode that was treated with immunosuppressive therapy.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [participants]
    25
    11.8%
    39
    18.2%
    45
    21.2%
    10. Secondary Outcome
    Title Number of Participants With Treatment Failure
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [participants]
    33
    15.6%
    31
    14.5%
    61
    28.8%
    11. Secondary Outcome
    Title Number of Participants Who Crossed Over Due to Treatment Failure
    Description 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.
    Time Frame one year

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number [participants]
    6
    2.8%
    10
    4.7%
    39
    18.4%
    12. Secondary Outcome
    Title Change From Month 1 in Serum Creatinine at Month 6 and Month 12
    Description Renal function was assessed by the change from Month 1 in serum creatinine six months and 12 months after transplant.
    Time Frame Month 1, Month 6, and Month 12

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set with available data at Month 1 and at each time point.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    At 6 months [N=184, 184, 169]
    -0.09
    (0.63)
    -0.08
    (0.56)
    -0.01
    (0.53)
    At 12 months [N=173, 182, 147]
    -0.08
    (0.76)
    -0.14
    (0.62)
    -0.04
    (0.53)
    13. Secondary Outcome
    Title Change From Month 1 in Creatinine Clearance at Month 6 and Month 12
    Description Renal function was assessed by creatinine clearance, calculated using the Cockcroft-Gault formula.
    Time Frame Month 1, Month 6, and Month 12

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set with available data at Month 1 and at each time point.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    At 6 months [N=184, 184, 167]
    0.83
    (13.77)
    0.47
    (12.90)
    -1.79
    (14.09)
    At 12 months [N=173, 182, 145]
    1.50
    (16.07)
    2.62
    (14.32)
    -0.25
    (14.54)
    14. Secondary Outcome
    Title Kaplan-Meier Estimate of Patient Survival at the End of the Study
    Description 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.
    Time Frame End of study (maximum time on study was 1,941 days).

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number (95% Confidence Interval) [percentage of participants]
    91.2
    43%
    93.2
    43.6%
    91.7
    43.3%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -0.5
    Confidence Interval (2-Sided) 95%
    -6.5 to 5.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 1.5
    Confidence Interval (2-Sided) 95%
    -3.9 to 6.9
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    15. Secondary Outcome
    Title Kaplan-Meier Estimate of Graft Survival at the End of the Study
    Description 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.
    Time Frame End of study (maximum time on study was 1,941 days).

    Outcome Measure Data

    Analysis Population Description
    The number of participants analyzed represents the full analysis set.
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    Measure Participants 212 214 212
    Number (95% Confidence Interval) [percentage of participants]
    82.7
    39%
    84.7
    39.6%
    83.9
    39.6%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Tacrolimus, Cyclosporine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value -1.3
    Confidence Interval (2-Sided) 95%
    -9.1 to 6.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Tacrolimus Modified Release, Cyclosporine
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value
    Comments
    Method
    Comments
    Method of Estimation Estimation Parameter Mean Difference (Final Values)
    Estimated Value 0.8
    Confidence Interval (2-Sided) 95%
    -7.1 to 8.6
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Up to 1941 days
    Adverse Event Reporting Description
    Arm/Group Title Tacrolimus Tacrolimus Modified Release Cyclosporine
    Arm/Group Description 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. 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. 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.
    All Cause Mortality
    Tacrolimus Tacrolimus Modified Release Cyclosporine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN) / (NaN)
    Serious Adverse Events
    Tacrolimus Tacrolimus Modified Release Cyclosporine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 148/212 (69.8%) 141/214 (65.9%) 139/212 (65.6%)
    Blood and lymphatic system disorders
    Anaemia 6/212 (2.8%) 4/214 (1.9%) 5/212 (2.4%)
    Thrombocytopenia 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Coagulopathy 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Febrile neutropenia 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Leukopenia 1/212 (0.5%) 0/214 (0%) 3/212 (1.4%)
    Normochromic normocytic anaemia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pancytopenia 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Thrombotic microangiopathy 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Haemolysis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Leukocytosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Lymphadenopathy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Neutropenia 0/212 (0%) 0/214 (0%) 2/212 (0.9%)
    Cardiac disorders
    Myocardial infarction 5/212 (2.4%) 4/214 (1.9%) 4/212 (1.9%)
    Coronary artery disease 4/212 (1.9%) 0/214 (0%) 1/212 (0.5%)
    Angina pectoris 3/212 (1.4%) 0/214 (0%) 1/212 (0.5%)
    Cardiac arrest 3/212 (1.4%) 1/214 (0.5%) 2/212 (0.9%)
    Cardiac failure congestive 3/212 (1.4%) 6/214 (2.8%) 1/212 (0.5%)
    Atrial fibrillation 2/212 (0.9%) 3/214 (1.4%) 3/212 (1.4%)
    Cardiac failure 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Acute coronary syndrome 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Aortic valve incompetence 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Atrial flutter 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Cardiac failure acute 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Myocardial ischaemia 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Pericarditis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Right ventricular failure 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Acute myocardial infarction 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Angina unstable 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Aortic valve disease 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Aortic valve stenosis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Atrioventricular block 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Atrioventricular block complete 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Atrioventricular block second degree 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Cardio respiratory arrest 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Cardiogenic shock 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Congestive cardiomyopathy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Coronary artery insufficiency 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Palpitations 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pericardial effusion 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Ventricular bigeminy 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Ventricular tachycardia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Congenital, familial and genetic disorders
    Congenital cystic kidney disease 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Anomalous pulmonary venous connection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Ear and labyrinth disorders
    Deafness 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Vertigo 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Endocrine disorders
    Hyperparathyroidism tertiary 3/212 (1.4%) 1/214 (0.5%) 0/212 (0%)
    Goitre 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Hyperparathyroidism 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Eye disorders
    Retinitis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Gastrointestinal disorders
    Diarrhoea 12/212 (5.7%) 10/214 (4.7%) 3/212 (1.4%)
    Vomiting 8/212 (3.8%) 8/214 (3.7%) 5/212 (2.4%)
    Nausea 7/212 (3.3%) 6/214 (2.8%) 3/212 (1.4%)
    Abdominal pain 5/212 (2.4%) 2/214 (0.9%) 5/212 (2.4%)
    Gastrointestinal haemorrhage 5/212 (2.4%) 0/214 (0%) 0/212 (0%)
    Abdominal hernia 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Diverticulitis 2/212 (0.9%) 3/214 (1.4%) 1/212 (0.5%)
    Enterocutaneous fistula 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Small intestinal obstruction 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Abdominal adhesions 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Abdominal pain upper 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Abdominal wall cyst 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Ascites 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Colitis 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Colitis ischaemic 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Constipation 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Diarhoea haemorrhagic 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Dyspepsia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Faecaloma 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Gastritis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Intestinal ischaemia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Intestinal obstruction 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Intestinal perforation 1/212 (0.5%) 0/214 (0%) 2/212 (0.9%)
    Oesophagitis 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Pancreatitis acute 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pancreatitis due to biliary obstruction 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Peritoneal haematoma 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Rectal polyp 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Rectal ulcer 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Subileus 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Umbilical hernia obstructive 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Abdominal haematoma 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Abdominal strangulated hernia 0/212 (0%) 0/214 (0%) 3/212 (1.4%)
    Abdominal wall disorder 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Acute abdomen 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Appendicitis perforated 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Duodenal ulcer 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Duodenal ulcer haemorrhage 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Food poisoning 0/212 (0%) 0/214 (0%) 2/212 (0.9%)
    Gastric ulcer 0/212 (0%) 0/214 (0%) 2/212 (0.9%)
    Gastric ulcer haemorhage 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Gastric ulcer perforation 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Gastritis erosive 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Gingival hyperplasia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Haemorrhoidal haemorrhage 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Ileus 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Impaired gastric emptying 0/212 (0%) 2/214 (0.9%) 2/212 (0.9%)
    Inguinal hernia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Oesophageal erosion 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Pancreatitis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pancreatitis haemorrhagic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Peritonitis 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Proctalgia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Rectal haemorrhage 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Retroperitoneal haematoma 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Salivary gland enlargement 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Umbilical hernia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Upper gastrointestinal haemorrhage 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    General disorders
    Pyrexia 5/212 (2.4%) 5/214 (2.3%) 8/212 (3.8%)
    Chest pain 2/212 (0.9%) 4/214 (1.9%) 0/212 (0%)
    Oedema peripheral 2/212 (0.9%) 1/214 (0.5%) 0/212 (0%)
    Adhesion 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Asthenia 1/212 (0.5%) 2/214 (0.9%) 1/212 (0.5%)
    Impaired healing 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Non-cardiac chest pain 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Systemic inflammatory response syndrome 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Anasarca 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Catheter site haemorrhage 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Fatigue 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Oedema 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Rigors 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Sudden death 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Swelling 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Ulcer haemorrhage 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hepatobiliary disorders
    Bile duct stone 2/212 (0.9%) 1/214 (0.5%) 0/212 (0%)
    Cholecystitis acute 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Cholelithiasis 1/212 (0.5%) 2/214 (0.9%) 2/212 (0.9%)
    Biliary colic 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Biliary dilatation 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Cholecystitis 0/212 (0%) 3/214 (1.4%) 1/212 (0.5%)
    Hepatic failure 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Hepatic lesion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Immune system disorders
    Graft loss 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Kidney transplant rejection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Anaphylactic reaction 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Infections and infestations
    Cytomegalovirus infection 15/212 (7.1%) 11/214 (5.1%) 11/212 (5.2%)
    Urinary tract infection 15/212 (7.1%) 11/214 (5.1%) 15/212 (7.1%)
    Human polyomavirus infection 9/212 (4.2%) 5/214 (2.3%) 1/212 (0.5%)
    Sepsis 6/212 (2.8%) 8/214 (3.7%) 4/212 (1.9%)
    Gastroenteritis viral 5/212 (2.4%) 0/214 (0%) 1/212 (0.5%)
    Urosepsis 5/212 (2.4%) 5/214 (2.3%) 5/212 (2.4%)
    Cellulitis 4/212 (1.9%) 5/214 (2.3%) 4/212 (1.9%)
    Gastroenteritis 4/212 (1.9%) 14/214 (6.5%) 3/212 (1.4%)
    Pneumonia 4/212 (1.9%) 10/214 (4.7%) 7/212 (3.3%)
    Pyelonephritis 4/212 (1.9%) 5/214 (2.3%) 3/212 (1.4%)
    Bronchitis 3/212 (1.4%) 2/214 (0.9%) 1/212 (0.5%)
    Escherichia urinary tract infection 3/212 (1.4%) 6/214 (2.8%) 5/212 (2.4%)
    Herpes zoster 3/212 (1.4%) 3/214 (1.4%) 1/212 (0.5%)
    Strongyloidiasis 3/212 (1.4%) 0/214 (0%) 0/212 (0%)
    Urinary tract infection bacterial 3/212 (1.4%) 3/214 (1.4%) 4/212 (1.9%)
    Bacteraemia 2/212 (0.9%) 2/214 (0.9%) 2/212 (0.9%)
    Bacterial pyelonephritis 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Cytomegalovirus colitis 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Cytomegalovirus viraemia 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Endocarditis 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Osteomyelitis 2/212 (0.9%) 2/214 (0.9%) 1/212 (0.5%)
    Subcutaneous abscess 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Urinary tract infection enterococcal 2/212 (0.9%) 1/214 (0.5%) 1/212 (0.5%)
    Abdominal abscess 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Abscess 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Abscess limb 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Bronchitis acute 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Bronchopneumonia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Bronchopulmonary aspergillosis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Catheter related infection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Catheter sepsis 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Clostridial infection 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Clostridium colitis 1/212 (0.5%) 2/214 (0.9%) 1/212 (0.5%)
    Diabetic foot infection 1/212 (0.5%) 0/214 (0%) 2/212 (0.9%)
    Diarrhoea infectious 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Escherichia bacteraemia 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Furuncle 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Infected cyst 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Infected skin ulcer 1/212 (0.5%) 3/214 (1.4%) 0/212 (0%)
    Klebsiella bacteraemia 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Lobar pneumonia 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Localised infection 1/212 (0.5%) 3/214 (1.4%) 1/212 (0.5%)
    Lung infection pseudomonal 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Mastoiditis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Mycobacterium avium complex infection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Orchitis 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Otitis media 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pharyngotonsillitis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pneumonia fungal 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pneumonia staphylococcal 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pyelonephritis acute 1/212 (0.5%) 0/214 (0%) 2/212 (0.9%)
    Skin bacterial infection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Staphylococcal bacteraemia 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Staphylococcal infection 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Streptococcal sepsis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Tracheobronchitis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Tuberculosis 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Urinary tract infection fungal 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Urinary tract infection pseudomonal 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Vancomycin resistant enterococcal infection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Viral infection 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Vulval abscess 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Wound infection 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Appendicitis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Cellulitis gangrenous 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Choriomeningitis lymphocytic 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Condyloma acuminatum 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Cytomegalovirus gastritis 0/212 (0%) 1/214 (0.5%) 2/212 (0.9%)
    Cytomegalovirus oesophagitis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Endocarditis bacterial 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Gastritis fungal 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Groin infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Helicobacter gastritis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Herpes virus infection 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Herpetic gingivostomatitis infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Influenza 0/212 (0%) 4/214 (1.9%) 1/212 (0.5%)
    Meningitits aseptic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Meningitits cryptococcal 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Oesophageal candidiasis 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Papilloma viral infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Parvovirus infection 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Perinephric abscess 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Pharyngitis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Phlebitis infective 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pneumonia haemophilus 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pneumonia klebsiella 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Postoperative abscess 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Postoperative infection 0/212 (0%) 1/214 (0.5%) 2/212 (0.9%)
    Respiratory tract infection 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Septic shock 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Sinusitis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Streptococcal bacteraemia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Streptococcal infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Tonsillitis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Urinary tract infection staphylococcal 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Vaginitis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Varicella 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Viral upper respiratory tract infection 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Injury, poisoning and procedural complications
    Complications of transplant surgery 5/212 (2.4%) 3/214 (1.4%) 2/212 (0.9%)
    Graft dysfunction 5/212 (2.4%) 3/214 (1.4%) 2/212 (0.9%)
    Therapeutic agent toxicity 5/212 (2.4%) 2/214 (0.9%) 1/212 (0.5%)
    Ankle fracture 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Fall 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Foot Fracture 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Incisional hernia 2/212 (0.9%) 1/214 (0.5%) 1/212 (0.5%)
    Subdural haematoma 2/212 (0.9%) 1/214 (0.5%) 0/212 (0%)
    Arteriovenous graft site complication 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Arteriovenous graft thrombosis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Cardiac pacemaker malfunction 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Drug toxicity 1/212 (0.5%) 1/214 (0.5%) 2/212 (0.9%)
    Femur fracture 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Hip fracture 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Incision site haemorrhage 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Perinephric collection 1/212 (0.5%) 1/214 (0.5%) 2/212 (0.9%)
    Perirenal haematoma 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Post procedural discharge 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Post procedural pain 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Post procedural urine leak 1/212 (0.5%) 2/214 (0.9%) 1/212 (0.5%)
    Postoperative haematoma 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Renal haematoma 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Ulna fracture 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Wound dehiscence 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Wrist fracture 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Acetabulum fracture 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Burns third degree 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Fibula fracture 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Graft complication 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Haematuria traumatic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Incision site complication 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Medical device compilation 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Meniscus lesion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pelvic fracture 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Post procedural haemorrhage 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Postoperative ileus 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Procedural complication 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Pubic rami fracture 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Renal injury 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Rib fracture 0/212 (0%) 2/214 (0.9%) 2/212 (0.9%)
    Road traffic accident 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Skin laceration 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Thoracic vertebral fracture 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Tibia fracture 0/212 (0%) 3/214 (1.4%) 0/212 (0%)
    Traumatic haematoma 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Wound secretion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Investigations
    Blood creatinine increased 18/212 (8.5%) 11/214 (5.1%) 15/212 (7.1%)
    Blood in stool 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Blood urea increased 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Cardiac stress test abnormal 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Haematocrit decreased 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Haemaglobin decreased 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Hepatic enzyme increased 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Volume blood decreased 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Blood creatine increased 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Blood glucose increased 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Cytomegalovirus test positive 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    International normalized ration increased 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Urine output decreased 0/212 (0%) 1/214 (0.5%) 3/212 (1.4%)
    Weight decreased 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Metabolism and nutrition disorders
    Dehydration 9/212 (4.2%) 10/214 (4.7%) 6/212 (2.8%)
    Hyperglycaemia 5/212 (2.4%) 5/214 (2.3%) 3/212 (1.4%)
    Hyperkalaemia 5/212 (2.4%) 5/214 (2.3%) 1/212 (0.5%)
    Diabetes mellitus inadequate control 4/212 (1.9%) 2/214 (0.9%) 2/212 (0.9%)
    Diabetes mellitus 2/212 (0.9%) 6/214 (2.8%) 4/212 (1.9%)
    Fluid overload 2/212 (0.9%) 1/214 (0.5%) 1/212 (0.5%)
    Hypocalcaemia 2/212 (0.9%) 1/214 (0.5%) 0/212 (0%)
    Hypovolaemia 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Diabetic foot 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Diabetic ketoacidosis 1/212 (0.5%) 4/214 (1.9%) 1/212 (0.5%)
    Gout 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Hypercalcaemia 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Hypoglycaemia 1/212 (0.5%) 1/214 (0.5%) 2/212 (0.9%)
    Hypokalaemia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Hyponatraemia 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Malnutrition 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Metabolic acidosis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Anorexia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Diabetes with hyperosmolarity 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Hypophosphataemia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Obesity 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Musculoskeletal and connective tissue disorders
    Osteoarthritis 2/212 (0.9%) 2/214 (0.9%) 0/212 (0%)
    Arthralgia 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Back pain 1/212 (0.5%) 0/214 (0%) 2/212 (0.9%)
    Intervertebral disc protrusion 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Monoarthritis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Musculoskeletal chest pain 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pain in extremity 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Rotator cuff syndrome 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Bone Spur 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Compartment syndrome 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Fistula 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Flank pain 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Fracture malunion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Gouty arthritis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Intervertebral disc space narrowing 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Joint swelling 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Localized osteoarthritis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Muscular weakness 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Plantar fasciitis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Spondylosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Systemic lupus erythematosus 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Squamous cell carcinoma 4/212 (1.9%) 2/214 (0.9%) 2/212 (0.9%)
    Prostate cancer 3/212 (1.4%) 0/214 (0%) 0/212 (0%)
    Adenoma benign 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Carcinoid tumour of the pancreas 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Cervix carcinoma 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Metastatic renal cell carcinoma 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Ovarian cancer 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Renal cell carcinoma stage unspecified 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Squamous cell carcinoma of skin 1/212 (0.5%) 3/214 (1.4%) 0/212 (0%)
    B-cell lymphoma 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Basal cell carcinoma 0/212 (0%) 2/214 (0.9%) 1/212 (0.5%)
    Bladder cancer 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Breast cancer 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Carcinoid tumour of the appendix 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Carcinoid tumour of the stomach 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Kaposi's sarcoma 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Laryngeal cancer 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Lung neoplasm malignant 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Lymphooroliferative disorder 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Uterine cancer 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Nervous system disorders
    Convulsion 3/212 (1.4%) 1/214 (0.5%) 1/212 (0.5%)
    Dizziness 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Headache 2/212 (0.9%) 3/214 (1.4%) 0/212 (0%)
    Cerebral haemorrhage 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Depressed level of consciousness 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Diabetic hypersmolar coma 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Dysaesthesia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Guillain Barre syndrome 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Sleep apnoea syndrome 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Sleep paralysis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Viith nerve paralysis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Cerebellar haemorrhage 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Cerebrovascular accident 0/212 (0%) 1/214 (0.5%) 2/212 (0.9%)
    Encephalitis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Hepatic encephalopathy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Lumbar radiculopathy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Migraine 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Multiple sclerosis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Neuropathy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Neuropathy peripheral 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Normal pressure hydrocephalus 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Parkinson's disease 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Syncope 0/212 (0%) 1/214 (0.5%) 2/212 (0.9%)
    Transient ischaemic attack 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Psychiatric disorders
    Depression 3/212 (1.4%) 3/214 (1.4%) 0/212 (0%)
    Mental status changes 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Psychotic disorder 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Anxiety 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Completed Suicide 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Confusional state 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Hallucination 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Major depression 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Suicidal ideation 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Renal and urinary disorders
    Renal failure acute 9/212 (4.2%) 4/214 (1.9%) 7/212 (3.3%)
    Renal Impairment 4/212 (1.9%) 3/214 (1.4%) 3/212 (1.4%)
    Hydronephrosis 3/212 (1.4%) 2/214 (0.9%) 4/212 (1.9%)
    Dysuria 2/212 (0.9%) 0/214 (0%) 2/212 (0.9%)
    Haematuria 2/212 (0.9%) 4/214 (1.9%) 4/212 (1.9%)
    Obstructive uropathy 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Renal insufficiency 2/212 (0.9%) 5/214 (2.3%) 0/212 (0%)
    Urinary incontinence 2/212 (0.9%) 0/214 (0%) 0/212 (0%)
    Bladder disorder 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Bladder neck obstruction 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Haemorrhage urinary tract 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Nephropathy 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Renal vein thrombosis 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Ureteric obstruction 1/212 (0.5%) 0/214 (0%) 1/212 (0.5%)
    Ureteric stenosis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Urinary retention 1/212 (0.5%) 1/214 (0.5%) 2/212 (0.9%)
    Acute prerenal failure 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Azotaemia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hydroureter 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Nephropathy Toxic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Nephrotic Syndrome 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Pelvi-ureteric obstruction 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Proteinuria 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Renal artery stenosis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Renal artery thrombosis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Renal failure chronic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Stress incontinence 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Urethral meatus stenosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Urethral obstruction 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Urinary tract obstruction 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Urinoma 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Reproductive system and breast disorders
    Epididymitis 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Menorrhagia 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Ovarian cyst 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Scrotal oedema 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Testicular infarction 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Vaginal haemorrhage 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Benign prostatic hyperplasia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Endometriosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Erectile dysfunction 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Gynaecomastia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Ovarian cyst torsion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pelvic muscles inadequate 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Priapism 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Prostatis 0/212 (0%) 3/214 (1.4%) 0/212 (0%)
    Uterovaginal prolapse 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism 6/212 (2.8%) 1/214 (0.5%) 3/212 (1.4%)
    Dyspnoea 2/212 (0.9%) 3/214 (1.4%) 2/212 (0.9%)
    Pulmonary hypertension 2/212 (0.9%) 1/214 (0.5%) 0/212 (0%)
    Respiratory failure 2/212 (0.9%) 3/214 (1.4%) 0/212 (0%)
    Dyspnoea exertional 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Laryngeal oedema 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Lung disorder 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pleural effusion 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Pneumonitis 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Pulmonary oedema 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Acute Respiratory failure 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Asthma 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Chronic Obstructive airways Disease 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Chronic Obstructive airways Disease exacerbated 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Dyspnoea exacerbated 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Epistaxis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Haemoptysis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hypoxia 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Maxillary sinusitis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pleurisy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Pleuritic pain 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Pneumothorax 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Restrictive pulmonary disease 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Skin and subcutaneous tissue disorders
    Skin ulcer 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Social circumstances
    Murder 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Treatment noncompliance 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Surgical and medical procedures
    Knee arthoplasty 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Nephrectomy 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Pancreas transplant 1/212 (0.5%) 1/214 (0.5%) 1/212 (0.5%)
    Parathyroidectomy 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Umbilical hernia repair 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Abdominal hernia repair 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Abdominal panniculectomy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Abdominoplasty 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Cholecystectomy 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Colostomy closure 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Coronary arterial stent insertion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hip arthroplasty 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hospitalisation 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Inguinal hernia repair 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Small intestinal resection 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Vascular disorders
    Deep vein thrombosis 7/212 (3.3%) 4/214 (1.9%) 4/212 (1.9%)
    Haematoma 2/212 (0.9%) 1/214 (0.5%) 2/212 (0.9%)
    Hypotension 2/212 (0.9%) 5/214 (2.3%) 2/212 (0.9%)
    Lymphocele 2/212 (0.9%) 1/214 (0.5%) 4/212 (1.9%)
    Arterial thrombosis limb 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Arterivenous Fistula, acquired 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Gangrene 1/212 (0.5%) 2/214 (0.9%) 2/212 (0.9%)
    Lymphorrhoea 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Orthostatic hypotension 1/212 (0.5%) 2/214 (0.9%) 1/212 (0.5%)
    Peripheral artery dissection 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Peripheral vascular disorder 1/212 (0.5%) 1/214 (0.5%) 0/212 (0%)
    Thrombosis 1/212 (0.5%) 2/214 (0.9%) 0/212 (0%)
    Vascular Insufficency 1/212 (0.5%) 0/214 (0%) 0/212 (0%)
    Aortic aneurysm 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Arterial stenosis limb 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Atherosclerosis 0/212 (0%) 2/214 (0.9%) 0/212 (0%)
    Femoral arterial stenosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Femoral artery occlusion 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Hypertension 0/212 (0%) 0/214 (0%) 3/212 (1.4%)
    Hypertensive crisis 0/212 (0%) 3/214 (1.4%) 2/212 (0.9%)
    Iliac artery stenosis 0/212 (0%) 0/214 (0%) 2/212 (0.9%)
    Intermittent Claudication 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Jugular vein thrombosis 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Peripheral artery aneurysm 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Peripheral ischaemia 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Peripheral occlusive disease 0/212 (0%) 1/214 (0.5%) 0/212 (0%)
    Phlebitis 0/212 (0%) 1/214 (0.5%) 1/212 (0.5%)
    Renovascular Hypertension 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Shock haemorrhagic 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Venous stenosis 0/212 (0%) 0/214 (0%) 1/212 (0.5%)
    Other (Not Including Serious) Adverse Events
    Tacrolimus Tacrolimus Modified Release Cyclosporine
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 208/212 (98.1%) 212/214 (99.1%) 208/212 (98.1%)
    Blood and lymphatic system disorders
    Anaemia 59/212 (27.8%) 68/214 (31.8%) 55/212 (25.9%)
    Leukopenia 33/212 (15.6%) 35/214 (16.4%) 25/212 (11.8%)
    Polycythaemia 13/212 (6.1%) 12/214 (5.6%) 9/212 (4.2%)
    Cardiac disorders
    Tachycardia 11/212 (5.2%) 9/214 (4.2%) 10/212 (4.7%)
    Endocrine disorders
    Hirsutism 0/212 (0%) 0/214 (0%) 18/212 (8.5%)
    Gastrointestinal disorders
    Diarrhoea 91/212 (42.9%) 94/214 (43.9%) 53/212 (25%)
    Constipation 68/212 (32.1%) 85/214 (39.7%) 82/212 (38.7%)
    Nausea 71/212 (33.5%) 74/214 (34.6%) 90/212 (42.5%)
    Vomiting 49/212 (23.1%) 51/214 (23.8%) 46/212 (21.7%)
    Dyspepsia 36/212 (17%) 32/214 (15%) 32/212 (15.1%)
    Abdominal pain 22/212 (10.4%) 26/214 (12.1%) 35/212 (16.5%)
    Abdominal pain upper 21/212 (9.9%) 16/214 (7.5%) 18/212 (8.5%)
    Flatulence 22/212 (10.4%) 15/214 (7%) 14/212 (6.6%)
    Abdominal distension 15/212 (7.1%) 11/214 (5.1%) 18/212 (8.5%)
    Loose stools 14/212 (6.6%) 11/214 (5.1%) 4/212 (1.9%)
    Gastrooesophageal reflux disease 5/212 (2.4%) 9/214 (4.2%) 12/212 (5.7%)
    Haemorrhoids 5/212 (2.4%) 12/214 (5.6%) 6/212 (2.8%)
    General disorders
    Oedema peripheral 72/212 (34%) 75/214 (35%) 97/212 (45.8%)
    Fatigue 22/212 (10.4%) 32/214 (15%) 26/212 (12.3%)
    Oedema 27/212 (12.7%) 17/214 (7.9%) 25/212 (11.8%)
    Pyrexia 20/212 (9.4%) 21/214 (9.8%) 28/212 (13.2%)
    Asthenia 22/212 (10.4%) 16/214 (7.5%) 22/212 (10.4%)
    Chest pain 16/212 (7.5%) 19/214 (8.9%) 12/212 (5.7%)
    Pain 8/212 (3.8%) 11/214 (5.1%) 14/212 (6.6%)
    Anasarca 8/212 (3.8%) 12/214 (5.6%) 4/212 (1.9%)
    Infections and infestations
    Urinary tract infection 49/212 (23.1%) 30/214 (14%) 42/212 (19.8%)
    Upper respiratory tract infection 24/212 (11.3%) 27/214 (12.6%) 29/212 (13.7%)
    Oral Candidiasis 9/212 (4.2%) 15/214 (7%) 13/212 (6.1%)
    Sinusitis 7/212 (3.3%) 15/214 (7%) 5/212 (2.4%)
    Injury, poisoning and procedural complications
    Incision site complication 46/212 (21.7%) 31/214 (14.5%) 42/212 (19.8%)
    Post procedural pain 42/212 (19.8%) 27/214 (12.6%) 37/212 (17.5%)
    Graft dysfunction 41/212 (19.3%) 27/214 (12.6%) 31/212 (14.6%)
    Post procedural discharge 6/212 (2.8%) 10/214 (4.7%) 12/212 (5.7%)
    Complications of transplant surgery 11/212 (5.2%) 5/214 (2.3%) 10/212 (4.7%)
    Investigations
    Blood creatinine increased 41/212 (19.3%) 32/214 (15%) 36/212 (17%)
    Weight increased 18/212 (8.5%) 14/214 (6.5%) 22/212 (10.4%)
    Blood magnesium decreased 19/212 (9%) 15/214 (7%) 12/212 (5.7%)
    Urine output decreased 8/212 (3.8%) 12/214 (5.6%) 10/212 (4.7%)
    Blood phosphorus decreased 10/212 (4.7%) 11/214 (5.1%) 6/212 (2.8%)
    Cardiac Murmur 11/212 (5.2%) 7/214 (3.3%) 5/212 (2.4%)
    Metabolism and nutrition disorders
    Hypophosphataemia 59/212 (27.8%) 50/214 (23.4%) 45/212 (21.2%)
    Hypomagnesaemia 57/212 (26.9%) 52/214 (24.3%) 44/212 (20.8%)
    Hyperkalaemia 48/212 (22.6%) 40/214 (18.7%) 38/212 (17.9%)
    Hyperlipidaemia 35/212 (16.5%) 35/214 (16.4%) 52/212 (24.5%)
    Hyperglycaemia 37/212 (17.5%) 30/214 (14%) 28/212 (13.2%)
    Hypokalaemia 31/212 (14.6%) 31/214 (14.5%) 33/212 (15.6%)
    Diabetes mellitus 20/212 (9.4%) 25/214 (11.7%) 9/212 (4.2%)
    Hypocalcaemia 15/212 (7.1%) 13/214 (6.1%) 25/212 (11.8%)
    Metabolic acidosis 12/212 (5.7%) 15/214 (7%) 11/212 (5.2%)
    Hypercholesterolaemia 10/212 (4.7%) 8/214 (3.7%) 16/212 (7.5%)
    Fluid overload 14/212 (6.6%) 9/214 (4.2%) 9/212 (4.2%)
    Dehydration 16/212 (7.5%) 10/214 (4.7%) 4/212 (1.9%)
    Dyslipidaemia 4/212 (1.9%) 12/214 (5.6%) 6/212 (2.8%)
    Musculoskeletal and connective tissue disorders
    Back pain 27/212 (12.7%) 32/214 (15%) 29/212 (13.7%)
    Arthralgia 26/212 (12.3%) 27/214 (12.6%) 28/212 (13.2%)
    Pain in Extremity 27/212 (12.7%) 27/214 (12.6%) 26/212 (12.3%)
    Muscle Cramp 17/212 (8%) 20/214 (9.3%) 22/212 (10.4%)
    Osteopenia 12/212 (5.7%) 13/214 (6.1%) 13/212 (6.1%)
    Nervous system disorders
    Tremor 73/212 (34.4%) 75/214 (35%) 42/212 (19.8%)
    Headache 50/212 (23.6%) 45/214 (21%) 52/212 (24.5%)
    Dizziness 27/212 (12.7%) 21/214 (9.8%) 23/212 (10.8%)
    Paraesthesia 3/212 (1.4%) 12/214 (5.6%) 13/212 (6.1%)
    Hypoaesthesia 5/212 (2.4%) 8/214 (3.7%) 11/212 (5.2%)
    Psychiatric disorders
    Insomnia 60/212 (28.3%) 52/214 (24.3%) 45/212 (21.2%)
    Anxiety 23/212 (10.8%) 27/214 (12.6%) 21/212 (9.9%)
    Depression 13/212 (6.1%) 11/214 (5.1%) 11/212 (5.2%)
    Renal and urinary disorders
    Dysuria 23/212 (10.8%) 15/214 (7%) 20/212 (9.4%)
    Haematuria 18/212 (8.5%) 15/214 (7%) 20/212 (9.4%)
    Proteinuria 5/212 (2.4%) 13/214 (6.1%) 10/212 (4.7%)
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea 22/212 (10.4%) 27/214 (12.6%) 26/212 (12.3%)
    Cough 26/212 (12.3%) 15/214 (7%) 21/212 (9.9%)
    Pharyngolaryngeal Pain 15/212 (7.1%) 16/214 (7.5%) 11/212 (5.2%)
    Dyspnoea exertional 12/212 (5.7%) 10/214 (4.7%) 8/212 (3.8%)
    Skin and subcutaneous tissue disorders
    Pruritus 20/212 (9.4%) 24/214 (11.2%) 15/212 (7.1%)
    Acne 13/212 (6.1%) 18/214 (8.4%) 22/212 (10.4%)
    Alopecia 15/212 (7.1%) 14/214 (6.5%) 4/212 (1.9%)
    Rash 10/212 (4.7%) 11/214 (5.1%) 5/212 (2.4%)
    Vascular disorders
    Hypertension 63/212 (29.7%) 59/214 (27.6%) 69/212 (32.5%)
    Hypotension 17/212 (8%) 19/214 (8.9%) 17/212 (8%)
    Orthostatic Hypotension 9/212 (4.2%) 15/214 (7%) 5/212 (2.4%)

    Limitations/Caveats

    Company makes no warranties or representations of any kind as to the posting, expressed or implied, including warranties of merchantability and fitness for a particular purpose, and shall not be liable for any damages.

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    Institute and/or Principal Investigator may publish trial data generated at their specific study site after Sponsor publication of the multi-center data or until 18 months have elapsed following study completion. Sponsor must receive a site's manuscript at least 30 days prior to publication to ensure that no confidential information of Sponsor is included in the document.

    Results Point of Contact

    Name/Title Vice President, Therapeutic Area Head, Transplantation
    Organization Astellas Pharma Global Development, Inc.
    Phone
    Email ClinicalTrials.Disclosure@us.astellas.com
    Responsible Party:
    Astellas Pharma Inc
    ClinicalTrials.gov Identifier:
    NCT00064701
    Other Study ID Numbers:
    • 02-0-158
    First Posted:
    Jul 14, 2003
    Last Update Posted:
    Dec 5, 2013
    Last Verified:
    Nov 1, 2013