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3C: Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy

Sponsor
University of Oxford (Other)
Overall Status
Completed
CT.gov ID
NCT01120028
Collaborator
National Health Service, United Kingdom (Other), Pfizer (Industry), Novartis (Industry)
852
Enrollment
20
Locations
4
Arms
114
Actual Duration (Months)
42.6
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The 3C study is investigating whether reducing exposure to calcineurin inhibitors (by using more potent antibody induction treatment and/or an elective switch to sirolimus) can improve the function and survival of kidney transplants.

Condition or Disease Intervention/Treatment Phase
Phase 2/Phase 3

Detailed Description

The long-term survival of kidney transplants has not improved over the past decade despite reductions in the rate of acute rejection. The commonest cause of late graft loss is chronic allograft nephropathy which is frequently caused by calcineurin inhibitor toxicity. Therefore, it may be possible to improve long-term graft outcomes by reducing the amount of calcineurin inhibitor exposure.

Two possible strategies to do this were tested. Firstly, Campath-1H (a monoclonal lymphocyte-depleting antibody) was compared to standard basiliximab-based induction. All patients then received tacrolimus-based maintenance therapy for 6-months (using lower doses in the Campath-1H arm).

At six months, patients were re-randomized between remaining on tacrolimus and converting to sirolimus (and therefore no longer taking calcineurin inhibitors). Patients were then followed-up in clinic and through routine NHS registries to collect information on relevant outcomes (including graft function, survival, hospitalisations and death).

Study Design

Study Type:
Interventional
Actual Enrollment :
852 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Open-label, Randomised Multicentre Study of CAMPATH-1H Versus Basiliximab Induction Treatment and Sirolimus Versus Tacrolimus Maintenance Treatment for the Preservation of Renal Function in Patients Receiving Kidney Transplants
Actual Study Start Date :
Sep 1, 2010
Actual Primary Completion Date :
Feb 1, 2014
Actual Study Completion Date :
Mar 1, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Alemtuzumab/Sirolimus

Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Sirolimus

Drug: Alemtuzumab
Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart
Other Names:
  • Campath-1H

    • Drug: Sirolimus
    Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
    Other Names:
  • Rapamune

    		•
    Experimental: Alemtuzumab/Tacrolimus

    Induction therapy allocation: Alemtuzumab (Campath-1H). Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus

    Drug: Alemtuzumab
    Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart
    Other Names:
  • Campath-1H

    • Drug: Tacrolimus
    Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
    Other Names:
  • Prograf

    		•
    Active Comparator: Basiliximab/Tacrolimus

    Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Tacrolimus

    Drug: Basiliximab
    20 mg intravenously, two doses 96 hours apart
    Other Names:
  • Simulect

    • Drug: Tacrolimus
    Tacrolimus: target trough levels 5-7 ng/mL after maintenance therapy randomization.
    Other Names:
  • Prograf

    		•
    Active Comparator: Basiliximab/Sirolimus

    Induction therapy allocation: Basiliximab. Maintenance therapy allocation (at 6-months post-transplant): Sirolimus

    Drug: Basiliximab
    20 mg intravenously, two doses 96 hours apart
    Other Names:
  • Simulect

    • Drug: Sirolimus
    Sirolimus: target trough levels 6-12 ng/mL for first 6-months after maintenance therapy randomization, then 5-10 ng/mL
    Other Names:
  • Rapamune

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy [6 months post-transplantation]

      Occurence of biopsy-proven acute rejection events at 6-months after transplantation during Period 1 (randomization to induction therapy (Campath-1H and Tacrolimus, or Basiliximab and Tacrolimus))

    2. Graft Function (at 18-months After Randomization to Maintenance Therapy) [2 years post-transplantation]

      Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.

    Secondary Outcome Measures

    1. Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy) [6 months post-transplantation]

      Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.

    2. Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy) [2 years post-transplantation]

      Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.

    3. Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy) [6-months post-transplantation]

      Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported within Period 1 (randomization to induction therapy of either Alemtuzumab (Campath-1H) and Tacrolimus, or Basiliximab and Tacrolimus).

    4. Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy) [2 years post-transplantation]

      Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).

    5. Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy) [2 years post-transplantation]

      Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).

    6. Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy) [2 years post-transplantation]

      Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • men or women aged over 18 years

    • recipient of kidney transplant (planned in next 24 hours)

    Exclusion Criteria:

    • recipients of multi-organ transplant

    • previous treatment with Campath-1H

    • active infection (including HIV, hepatitis B or C)

    • history of anaphylaxis to humanized monoclonal antibody

    • history of malignancy (except adequately treated non-melanoma skin cancer)

    • loss of kidney transplant within 6 months not due to technical reasons

    • medical history that might limit the individual's ability to take trial treatments for the duration of the study

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Oxford Radcliffe Hospitals NHS Trust Oxford Oxon United Kingdom OX3 7LJ
    2 University Hospitals Birmingham NHS Foundation Trust Birmingham United Kingdom
    3 Addenbrooke's Hospital NHS Trust Cambridge United Kingdom
    4 University Hospital of Wales Cardiff United Kingdom
    5 University Hospitals Coventry & Warwickshire Coventry United Kingdom
    6 Royal Infirmary Edinburgh United Kingdom
    7 Western Infirmary Glasgow United Kingdom
    8 Hull and East Yorkshire Hospitals NHS Trust Hull United Kingdom
    9 Leeds Teaching Hospitals NHS Trust Leeds United Kingdom
    10 Royal Liverpool and Broadgreen University Hospitals NHS Trust Liverpool United Kingdom
    11 Bart's and the London NHS Trust London United Kingdom
    12 Guy's and St Thomas's NHS Trust London United Kingdom
    13 Kings College Hospital NHS Trust London United Kingdom
    14 Royal Free Hampstead NHS Trust London United Kingdom
    15 Central Manchester NHS Trust Manchester United Kingdom
    16 Newcastle-upon-Tyne Hospitals NHS Trust Newcastle United Kingdom
    17 Nottingham University Hospitals NHS Trust Nottingham United Kingdom
    18 Plymouth Teaching Hospitals NHS Trust Plymouth United Kingdom
    19 Portsmouth Hospitals NHS Trust Portsmouth United Kingdom
    20 Sheffield Teaching Hospitals NHS Trust Sheffield United Kingdom

    Sponsors and Collaborators

    • University of Oxford
    • National Health Service, United Kingdom
    • Pfizer
    • Novartis

    Investigators

    • Study Director: Peter Friend, University of Oxford
    • Principal Investigator: Colin Baigent, University of Oxford
    • Principal Investigator: Martin J Landray, University of Oxford
    • Principal Investigator: Paul Harden, University of Oxford
    • Principal Investigator: Richard Haynes, University of Oxford

    Study Documents (Full-Text)

    More Information

    Additional Information:

    Publications

    None provided.
    Responsible Party:
    University of Oxford
    ClinicalTrials.gov Identifier:
    NCT01120028
    Other Study ID Numbers:
    • CTSU3C1
    • 2008-008553-27
    • ISRCTN88894088
    First Posted:
    May 10, 2010
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Keywords provided by University of Oxford
    Kidney transplantation
    Alemtuzumab
    Sirolimus
    Basiliximab
    Tacrolimus
    Campath-1H
    Additional relevant MeSH terms:
    Sirolimus
    Alemtuzumab
    Tacrolimus
    Basiliximab

    Study Results

    Participant Flow

    Recruitment Details 3C was conducted in 18 transplant centres in the UK. Recruitment took place between October 2010 and July 2013.
    Pre-assignment Detail 852 participants were randomized for a comparison of Alemtuzumab (426) and Basiliximab (426) based induction therapies. After 6-months, 394 of those participants were re-randomized to either Sirolimus (197) or Tacrolimus (197) based maintenance therapies.
    Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Period Title: Period 1: Alemtuzumab or Basiliximab
    STARTED 426 426 0 0
    COMPLETED 412 403 0 0
    NOT COMPLETED 14 23 0 0
    Period Title: Period 1: Alemtuzumab or Basiliximab
    STARTED 0 0 197 197
    COMPLETED 0 0 197 197
    NOT COMPLETED 0 0 0 0

    Baseline Characteristics

    Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus Total
    Arm/Group Description Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart. Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart. Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab. Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL. Total of all reporting groups
    Overall Participants 426 426 197 197 1246
    Age (Count of Participants)
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    347
    81.5%
    350
    82.2%
    0
    0%
    0
    0%
    697
    55.9%
    >=65 years
    79
    18.5%
    76
    17.8%
    0
    0%
    0
    0%
    155
    12.4%
    <=18 years
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    0
    0%
    Between 18 and 65 years
    0
    0%
    0
    0%
    163
    82.7%
    162
    82.2%
    325
    26.1%
    >=65 years
    0
    0%
    0
    0%
    34
    17.3%
    35
    17.8%
    69
    5.5%
    Age (years) [Mean (Standard Deviation) ]
    Age, Continuous, Period 1
    52.1
    (13.3)
    51.8
    (13.3)
    51.9
    (13.3)
    Age, Continuous, Period 2
    51.7
    (13.0)
    52.0
    (12.9)
    51.8
    (13.0)
    Sex: Female, Male (Count of Participants)
    Female
    149
    35%
    151
    35.4%
    0
    0%
    0
    0%
    300
    24.1%
    Male
    277
    65%
    275
    64.6%
    0
    0%
    0
    0%
    552
    44.3%
    Female
    0
    0%
    0
    0%
    65
    33%
    65
    33%
    130
    10.4%
    Male
    0
    0%
    0
    0%
    132
    67%
    132
    67%
    264
    21.2%
    Race/Ethnicity, Customized (Count of Participants)
    White
    370
    86.9%
    372
    87.3%
    0
    0%
    0
    0%
    742
    59.6%
    Black
    21
    4.9%
    21
    4.9%
    0
    0%
    0
    0%
    42
    3.4%
    Asian
    30
    7%
    23
    5.4%
    0
    0%
    0
    0%
    53
    4.3%
    Other
    5
    1.2%
    10
    2.3%
    0
    0%
    0
    0%
    15
    1.2%
    White
    0
    0%
    0
    0%
    174
    88.3%
    173
    87.8%
    347
    27.8%
    Black
    0
    0%
    0
    0%
    5
    2.5%
    7
    3.6%
    12
    1%
    Asian
    0
    0%
    0
    0%
    13
    6.6%
    15
    7.6%
    28
    2.2%
    Other
    0
    0%
    0
    0%
    5
    2.5%
    2
    1%
    7
    0.6%
    Region of Enrollment (Count of Participants)
    Period 1: United Kingdom
    426
    100%
    426
    100%
    0
    0%
    0
    0%
    852
    68.4%
    Period 2: United Kingdom
    0
    0%
    0
    0%
    197
    100%
    197
    100%
    394
    31.6%
    Primary Renal Disease (Count of Participants)
    Diabetic kidney disease
    51
    12%
    49
    11.5%
    0
    0%
    0
    0%
    100
    8%
    Glomerulonephritis
    92
    21.6%
    89
    20.9%
    0
    0%
    0
    0%
    181
    14.5%
    Polycystic kidney disease
    68
    16%
    73
    17.1%
    0
    0%
    0
    0%
    141
    11.3%
    Chronic pyelonephritis
    23
    5.4%
    16
    3.8%
    0
    0%
    0
    0%
    39
    3.1%
    Hypertension
    42
    9.9%
    42
    9.9%
    0
    0%
    0
    0%
    84
    6.7%
    Renovascular disease
    7
    1.6%
    6
    1.4%
    0
    0%
    0
    0%
    13
    1%
    Other
    143
    33.6%
    151
    35.4%
    0
    0%
    0
    0%
    294
    23.6%
    Diabetic kidney disease
    0
    0%
    0
    0%
    15
    7.6%
    21
    10.7%
    36
    2.9%
    Glomerulonephritis
    0
    0%
    0
    0%
    50
    25.4%
    40
    20.3%
    90
    7.2%
    Polycystic kidney disease
    0
    0%
    0
    0%
    47
    23.9%
    34
    17.3%
    81
    6.5%
    Chronic pyelonephritis
    0
    0%
    0
    0%
    5
    2.5%
    9
    4.6%
    14
    1.1%
    Hypertension
    0
    0%
    0
    0%
    14
    7.1%
    24
    12.2%
    38
    3%
    Renovascular disease
    0
    0%
    0
    0%
    3
    1.5%
    4
    2%
    7
    0.6%
    Other
    0
    0%
    0
    0%
    63
    32%
    65
    33%
    128
    10.3%
    Other Previous Disease (participants) [Number]
    Diabetes
    74
    17.4%
    67
    15.7%
    141
    71.6%
    Vascular Disease
    57
    13.4%
    49
    11.5%
    106
    53.8%
    Cancer
    18
    4.2%
    5
    1.2%
    23
    11.7%
    Previous renal replacement (Count of Participants)
    Haemodialysis
    243
    57%
    214
    50.2%
    0
    0%
    0
    0%
    457
    36.7%
    Peritoneal dialysis
    104
    24.4%
    106
    24.9%
    0
    0%
    0
    0%
    210
    16.9%
    Transplant
    3
    0.7%
    3
    0.7%
    0
    0%
    0
    0%
    6
    0.5%
    None
    76
    17.8%
    103
    24.2%
    0
    0%
    0
    0%
    179
    14.4%
    HLA mismatch level (Count of Participants)
    Level 1
    45
    10.6%
    47
    11%
    0
    0%
    0
    0%
    92
    7.4%
    Level 2
    94
    22.1%
    94
    22.1%
    0
    0%
    0
    0%
    188
    15.1%
    Level 3
    196
    46%
    193
    45.3%
    0
    0%
    0
    0%
    389
    31.2%
    Level 4
    91
    21.4%
    92
    21.6%
    0
    0%
    0
    0%
    183
    14.7%
    Level 1
    0
    0%
    0
    0%
    23
    11.7%
    22
    11.2%
    45
    3.6%
    Level 2
    0
    0%
    0
    0%
    42
    21.3%
    42
    21.3%
    84
    6.7%
    Level 3
    0
    0%
    0
    0%
    89
    45.2%
    90
    45.7%
    179
    14.4%
    Level 4
    0
    0%
    0
    0%
    43
    21.8%
    43
    21.8%
    86
    6.9%
    Previous transplant (Count of Participants)
    None
    390
    91.5%
    392
    92%
    0
    0%
    0
    0%
    782
    62.8%
    ≥1
    36
    8.5%
    34
    8%
    0
    0%
    0
    0%
    70
    5.6%
    None
    0
    0%
    0
    0%
    181
    91.9%
    181
    91.9%
    362
    29.1%
    ≥1
    0
    0%
    0
    0%
    16
    8.1%
    16
    8.1%
    32
    2.6%
    Highly sensitised (Count of Participants)
    Yes
    16
    3.8%
    15
    3.5%
    0
    0%
    0
    0%
    31
    2.5%
    No
    410
    96.2%
    411
    96.5%
    0
    0%
    0
    0%
    821
    65.9%
    Yes
    0
    0%
    0
    0%
    4
    2%
    7
    3.6%
    11
    0.9%
    No
    0
    0%
    0
    0%
    193
    98%
    190
    96.4%
    383
    30.7%
    Virology serology (Number) [Number]
    CMV-positive donor to negative recipient
    104
    24.4%
    102
    23.9%
    206
    104.6%
    EBV-positive donor to negative recipient
    21
    4.9%
    19
    4.5%
    40
    20.3%
    Type of donor (Count of Participants)
    Donation after brain death
    148
    34.7%
    145
    34%
    0
    0%
    0
    0%
    293
    23.5%
    Donation after circulatory death
    158
    37.1%
    158
    37.1%
    0
    0%
    0
    0%
    316
    25.4%
    Donation from living (related or unrelated) person
    120
    28.2%
    123
    28.9%
    0
    0%
    0
    0%
    243
    19.5%
    Donation after brain death
    0
    0%
    0
    0%
    66
    33.5%
    65
    33%
    131
    10.5%
    Donation after circulatory death
    0
    0%
    0
    0%
    65
    33%
    69
    35%
    134
    10.8%
    Donation from living (related or unrelated) person
    0
    0%
    0
    0%
    66
    33.5%
    63
    32%
    129
    10.4%
    Donor sex (Count of Participants)
    Male
    215
    50.5%
    207
    48.6%
    0
    0%
    0
    0%
    422
    33.9%
    Female
    193
    45.3%
    179
    42%
    0
    0%
    0
    0%
    372
    29.9%
    Unknown
    18
    4.2%
    40
    9.4%
    0
    0%
    0
    0%
    58
    4.7%
    Cold ischaemia time (h) (Hours) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Hours]
    13.9
    (5.7)
    12.9
    (6.0)
    13.4
    (5.9)

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy
    Description Occurence of biopsy-proven acute rejection events at 6-months after transplantation during Period 1 (randomization to induction therapy (Campath-1H and Tacrolimus, or Basiliximab and Tacrolimus))
    Time Frame 6 months post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus
    Arm/Group Description Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab
    Measure Participants 426 426
    Count of Participants [Participants]
    31
    7.3%
    68
    16%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value <0.0001
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 0.42
    Confidence Interval (2-Sided) 95%
    0.28 to 0.64
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Primary Outcome
    Title Graft Function (at 18-months After Randomization to Maintenance Therapy)
    Description Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.
    Time Frame 2 years post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Measure Participants 197 197
    Mean (Standard Error) [mL/min/1.73m²]
    53.7
    (0.9)
    54.6
    (0.9)
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.5
    Comments
    Method ANCOVA
    Comments
    3. Secondary Outcome
    Title Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)
    Description Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.
    Time Frame 6 months post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus
    Arm/Group Description Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab
    Measure Participants 426 426
    Count of Participants [Participants]
    16
    3.8%
    13
    3.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.58
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Hazard Ratio (HR)
    Estimated Value 1.23
    Confidence Interval (2-Sided) 95%
    0.59 to 2.55
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    4. Secondary Outcome
    Title Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)
    Description Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.
    Time Frame 2 years post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Measure Participants 197 197
    Count of Participants [Participants]
    8
    1.9%
    4
    0.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.23
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 1.99
    Confidence Interval (2-Sided) 95%
    0.64 to 6.18
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    5. Secondary Outcome
    Title Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)
    Description Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported within Period 1 (randomization to induction therapy of either Alemtuzumab (Campath-1H) and Tacrolimus, or Basiliximab and Tacrolimus).
    Time Frame 6-months post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 1: Campath 1H/Tacrolimus Period 1: Basiliximab/Tacrolimus
    Arm/Group Description Induction therapy allocation: Campath-1H and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab
    Measure Participants 426 426
    Count of Participants [Participants]
    135
    31.7%
    136
    31.9%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.88
    Comments
    Method Regression, Cox
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 1.02
    Confidence Interval (2-Sided) 95%
    0.80 to 1.29
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    6. Secondary Outcome
    Title Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)
    Description Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
    Time Frame 2 years post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Measure Participants 197 197
    Count of Participants [Participants]
    95
    22.3%
    70
    16.4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.008
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Rate ratio
    Estimated Value 1.51
    Confidence Interval (2-Sided) 95%
    1.11 to 2.06
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    7. Secondary Outcome
    Title Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)
    Description Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
    Time Frame 2 years post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Measure Participants 197 197
    Count of Participants [Participants]
    17
    4%
    17
    4%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.99
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 1.00
    Confidence Interval (2-Sided) 95%
    0.51 to 1.97
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    8. Secondary Outcome
    Title Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)
    Description Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
    Time Frame 2 years post-transplantation

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
    Measure Participants 197 197
    Count of Participants [Participants]
    10
    2.3%
    13
    3.1%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
    Comments
    Type of Statistical Test Other
    Comments
    Statistical Test of Hypothesis p-Value 0.52
    Comments
    Method Log Rank
    Comments
    Method of Estimation Estimation Parameter Rate Ratio
    Estimated Value 0.76
    Confidence Interval (2-Sided) 95%
    0.34 to 1.73
    Parameter Dispersion Type:
    Value:
    Estimation Comments

    Adverse Events

    Time Frame Period 1: SAEs collected during the 6-months post-transplantation Period 2: SAEs collected between 6-months and 24-months post-transplantation
    Adverse Event Reporting Description Information about the occurrence of serious adverse events was recorded at scheduled visits Other (not including Serious) Adverse Events were not recorded or assessed.
    Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
    Arm/Group Description Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab. Induction therapy allocation: Basiliximab and Tacrolimus Basiliximab: 20 mg intravenously, two doses 96 hours apart Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab Maintenance therapy allocation: Sirolimus Target trough level of 6-12 ng/mL for the first 6-months then reducing to 5-10 ng/nL Maintenancy therapy allocation: Tacrolimus Target trough level of 5-7 ng/mL
    All Cause Mortality
    Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 11/426 (2.6%) 6/426 (1.4%) 11/197 (5.6%) 9/197 (4.6%)
    Serious Adverse Events
    Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 341/426 (80%) 354/426 (83.1%) 140/197 (71.1%) 134/197 (68%)
    Blood and lymphatic system disorders
    Blood and lymphatic system disorders 26/426 (6.1%) 15/426 (3.5%) 3/197 (1.5%) 7/197 (3.6%)
    Cardiac disorders
    Cardiac disorders 14/426 (3.3%) 15/426 (3.5%) 10/197 (5.1%) 3/197 (1.5%)
    Congenital, familial and genetic disorders
    Congenital, familial and genetic disorders 0/426 (0%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Ear and labyrinth disorders
    Ear and labyrinth disorders 1/426 (0.2%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Endocrine disorders
    Endocrine disorders 0/426 (0%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Eye disorders
    Eye disorders 0/426 (0%) 0/426 (0%) 1/197 (0.5%) 0/197 (0%)
    Gastrointestinal disorders
    Gastrointestinal disorders 39/426 (9.2%) 40/426 (9.4%) 27/197 (13.7%) 25/197 (12.7%)
    General disorders
    General disorders and administration site conditions 22/426 (5.2%) 13/426 (3.1%) 5/197 (2.5%) 2/197 (1%)
    Hepatobiliary disorders
    Hepatobiliary disorders 1/426 (0.2%) 1/426 (0.2%) 3/197 (1.5%) 2/197 (1%)
    Immune system disorders
    Immune system disorders 41/426 (9.6%) 70/426 (16.4%) 33/197 (16.8%) 9/197 (4.6%)
    Infections and infestations
    Infections and infestations 158/426 (37.1%) 161/426 (37.8%) 97/197 (49.2%) 74/197 (37.6%)
    Injury, poisoning and procedural complications
    Injury, poisoning and procedural complications 154/426 (36.2%) 131/426 (30.8%) 13/197 (6.6%) 7/197 (3.6%)
    Investigations
    Investigations 140/426 (32.9%) 136/426 (31.9%) 24/197 (12.2%) 26/197 (13.2%)
    Metabolism and nutrition disorders
    Metabolism and nutrition disorders 20/426 (4.7%) 23/426 (5.4%) 19/197 (9.6%) 18/197 (9.1%)
    Musculoskeletal and connective tissue disorders
    Musculoskeletal and connective tissue disorders 3/426 (0.7%) 3/426 (0.7%) 3/197 (1.5%) 4/197 (2%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps) 6/426 (1.4%) 7/426 (1.6%) 18/197 (9.1%) 17/197 (8.6%)
    Nervous system disorders
    Nervous system disorders 10/426 (2.3%) 13/426 (3.1%) 8/197 (4.1%) 13/197 (6.6%)
    Pregnancy, puerperium and perinatal conditions
    Pregnancy, puerperium and perinatal conditions 0/426 (0%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Psychiatric disorders
    Psychiatric disorders 5/426 (1.2%) 2/426 (0.5%) 0/197 (0%) 1/197 (0.5%)
    Renal and urinary disorders
    Renal and urinary disorders 24/426 (5.6%) 37/426 (8.7%) 7/197 (3.6%) 9/197 (4.6%)
    Reproductive system and breast disorders
    Reproductive system and breast disorders 1/426 (0.2%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Respiratory, thoracic and mediastinal disorders
    Respiratory, thoracic and mediastinal disorders 7/426 (1.6%) 15/426 (3.5%) 7/197 (3.6%) 4/197 (2%)
    Skin and subcutaneous tissue disorders
    Skin and subcutaneous tissue disorders 2/426 (0.5%) 1/426 (0.2%) 2/197 (1%) 4/197 (2%)
    Social circumstances
    Social circumstances 0/426 (0%) 0/426 (0%) 0/197 (0%) 0/197 (0%)
    Surgical and medical procedures
    Surgical and medical procedures 190/426 (44.6%) 190/426 (44.6%) 39/197 (19.8%) 35/197 (17.8%)
    Vascular disorders
    Vascular disorders 13/426 (3.1%) 14/426 (3.3%) 3/197 (1.5%) 2/197 (1%)
    Other (Not Including Serious) Adverse Events
    Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 0/0 (NaN) 0/0 (NaN) 0/0 (NaN) 0/0 (NaN)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    All Principal Investigators ARE employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Prof Peter Friend
    Organization University of Oxford
    Phone 01865223872
    Email ccc@ctsu.ox.ac.uk
    Responsible Party:
    University of Oxford
    ClinicalTrials.gov Identifier:
    NCT01120028
    Other Study ID Numbers:
    • CTSU3C1
    • 2008-008553-27
    • ISRCTN88894088
    First Posted:
    May 10, 2010
    Last Update Posted:
    Apr 2, 2020
    Last Verified:
    Mar 1, 2020