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A Study to Evaluate the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation

Sponsor
Hoffmann-La Roche (Industry)
Overall Status
Completed
CT.gov ID
NCT00048165
Collaborator
(none)
434
Enrollment
30
Locations
2
Arms
36
Duration (Months)
14.5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of the study is to compare the number of randomized participants in each treatment group who experience an acute rejection episode in the first 6 months after undergoing cardiac transplantation.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
434 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double
Primary Purpose:
Treatment
Official Title:
A Double-Blind, Placebo -Controlled, Randomized Study to Assess the Efficacy and Safety of Zenapax in Combination With CellCept, Cyclosporine, and Corticosteroids in Patients Undergoing Cardiac Transplantation.
Study Start Date :
Aug 1, 1999
Actual Primary Completion Date :
Aug 1, 2002
Actual Study Completion Date :
Aug 1, 2002

Arms and Interventions

Arm Intervention/Treatment
Experimental: Daclizumab

Daclizumab will be administered as a intravenous dose of 1 milligrams per kilogram [mg/kg] on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg, and 500-1000 mg IV methylprednisolone peri operative switch to oral at 0.5-1 mg/kg/day followed by tapering.

Drug: Daclizumab
Daclizumab will be administered as 1 mg/kg IV within 12 hours post-op (Day 1), and Days 8, 22, 36 and 50.
Other Names:
  • Zenapax

    • Drug: Methylprednisolone
    Methylprednisolone will be administered as 500-1000 mg IV and peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering till 0.0-0.15 mg/kg/day (up to 365 days).

    Drug: Mycophenolate mofetil
    Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.

    Drug: cyclosporine
    Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.
    Placebo Comparator: Placebo

    Matching placebo will be administered on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine 1-4 mg/kg IV or 2-6 mg/kg orally, and 500-1000 mg IV methylprednisolone peri-op switch to oral at 0.5-1 mg/kg/day followed by tapering.

    Drug: Methylprednisolone
    Methylprednisolone will be administered as 500-1000 mg IV and peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering till 0.0-0.15 mg/kg/day (up to 365 days).

    Drug: Mycophenolate mofetil
    Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.

    Drug: Placebo
    Matching placebo will be administered on Days 1, 8, 22, 36, and 50.

    Drug: cyclosporine
    Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant [Up to 6 months PT]

      The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months post-transplant (PT). Participants with acute rejection included participants with a biopsy histology of International Society of Heart and Lung Transplant (ISHLT) Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up.

    Secondary Outcome Measures

    1. Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT [Up to 12 months PT]

      The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months. Participants with acute rejection included participants with a biopsy histology of ISHLT Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up

    2. Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT [Within 6 months and 12 months PT]

      The number of participants with 0,1, 2, 3 or 4 episodes at 6 and 12 months PT were reported. An episode of acute rejection was defined according to the date of positive biopsy of Grade IIIA or worse or the date of start of treatment for HDC, whichever came first.

    3. Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT [At 6 months, 12 months , 3 years PT]

      The survival of the graft and participants at 6,12 months and 3 years PT was reported

    4. Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT [Within 6 months and 12 months PT]

      The number of participants with Worst International Society of Heart and Lung Transplant (ISHLT) grade within first 6 months and 12 months PT were reported. ISHLT is a standardized grading method to determine the acute cellular rejection on endomyocardial biopsy ; where 0= no rejection, IA= focal (perivascular or interstitial) infiltrate without necrosis, IB= diffuse but sparse infiltrate without necrosis, II=one focus only with aggressive infiltration and/or focal myocyte damage, IIIA=multifocal aggressive infiltrates and/or myocyte damage, IIIB= diffuse inflammatory process with necrosis, IV= diffuse aggressive polymorphous and/or infiltrate and/or edema and/or hemorrhage and/or vasculitis, with necrosis

    5. Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT [Within 6 months and 12 months PT]

      The median time to first acute rejection episode within first 6 months and 12 months PT was reported.

    6. Number of Participants Using Monomurab Cluster of Differentiation 3, Orthoclone Polyclonal Antithymocyte Globulin or Antilymphocyte Globulin in the First 6 Months and 12 Months PT [Within 6 months and 12 months PT]

      The number of participants who received monomurab Cluster of differentiation 3, orthoclone, polyclonal antithymocyte globulin or antilymphocyte globulin for treatment of biopsy proven rejection or HDC within 6 and 12 months PT were reported.

    7. Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT [Within 6 months and 12 months PT]

      The maintenance doses of mycophenolate mofetil (1.5g twice a day daily), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg oral [PO]/nasogastric [NG] within 72 hours post-operative]), and cumulative dose of corticosteroids (500-1000 mg IV methylprednisolone pre-operative switched to oral at 0.5-1 mg/kg/day. Tapered to 0.2 mg/kg/d by Day 28, 0.1-0.15 mg/kg/day from Days 36 to 90, and 0.1-0.15 mg/kg/day from Days 120 to 180)at 6 and 12 months PT were reported. Maintenance dose was calculated as total dose per day summed over all days that a participant was administered drug within the specified time interval, divided by number of days that a participant took drug within that time interval.

    8. Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) [From Baseline (Day -2) to 3 months and 6 months]

      Lipid profile included total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (all total cholesterol, LDL, HDL, and triglycerides with unit milligram per decilitre [mg/dL]), were reported. The median change from baseline (Day -2) in lipid profile values at 3 months and 6 months was reported.

    9. Median Change From Baseline for LDL/HDL Ratio [From Baseline (Day -2) to 3 months, and 6 months]

    10. Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters [Up to 12 months]

      A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Hematology included hemoglobin, hematocrit, white blood cell count (WBC) with differential (including granulocytes or neutrophils, basophils, eosinophils, monocytes, lymphocytes), platelets, and erythrocyte count

    11. Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters [Up to 12 months]

      A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Biochemistry included blood urea nitrogen, creatinine, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transferase (GGT), phosphorous, total bilirubin, direct bilirubin, total protein, albumin, glucose, alkaline phosphatase, low density lipoprotein (LDH), uric acid, carbon dioxide, magnesium, sodium, potassium, chloride, calcium, LDL, HDL, total cholesterol, and triglycerides.

    12. Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal [Up to 12 months]

      An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during this study were reported as AEs. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.

    13. Number of Participants With Malignancies and Opportunistic Infections [Up to 12 months]

      The opportunistic infections included infections with Cytomegalovirus, Aspergillus, Candida, Pneumocystis, Cryptococcus, Listeria, Herpes simplex, Herpes zoster. For malignancy, participants with any type of malignancy whose date of onset or diagnosis was after randomization was reported.

    Eligibility Criteria

    Criteria

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

    • Participants must be undergoing their first cardiac allograft transplant

    • Women of childbearing potential must have a negative serum pregnancy test within 48 hours prior to transplantation

    • Women of childbearing potential must use two reliable forms of contraception simultaneously. Effective contraception must be used before beginning study drug therapy, and for 4 months following discontinuation of study drug therapy

    • Participants and/or their guardians must be willing and be capable of understanding risks and comply with the purpose of the study

    Exclusion Criteria:

    • Previous organ transplants

    • Participants receiving multiple organs

    • Participants requiring ventricular assist device (VAD) upon completion of transplantation surgery

    • Women lactating, pregnant or of childbearing potential not using, or who are unwilling to use two reliable forms of contraception simultaneously during the study

    • History of a psychological illness or condition which would interfere with the participant's ability to understand the requirements of the study

    • White blood count =<2500/mm3, platelets =<50,000/mm3 or hemoglobin =<6 g/dL

    • HIV-1, the presence of positive HBsAg, or chronic active hepatitis C

    • Active peptic ulcer disease

    • Severe diarrhea or other gastrointestinal disorders which might interfere with their ability to absorb oral medication

    • Malignancies within the past 5 years, excluding skin carcinoma that have been adequately treated

    • Participants who have received within the past 30 days or require concomitant treatment with other investigational drugs or immunosuppressive medications that are prohibited for this study

    • Inability to start microemulsion form of cyclosporine within 72 hours

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Birmingham Alabama United States 35294-0006
    2 Los Angeles California United States 90095
    3 Tampa Florida United States 33606
    4 Louisville Kentucky United States 40202
    5 Baltimore Maryland United States 21287
    6 Boston Massachusetts United States 02111
    7 Boston Massachusetts United States 02115
    8 Ann Arbor Michigan United States 48109-0366
    9 Minneapolis Minnesota United States 55455
    10 Albuquerque New Mexico United States 87106
    11 New York New York United States 10032
    12 Durham North Carolina United States 27710
    13 Cincinnati Ohio United States 45267-0542
    14 Cleveland Ohio United States 44195
    15 Portland Oregon United States 97201
    16 Philadelphia Pennsylvania United States 19104
    17 Philadelphia Pennsylvania United States 19140
    18 Pittsburgh Pennsylvania United States 15213-2582
    19 Charleston South Carolina United States 29425-2221
    20 Dallas Texas United States 75230
    21 Dallas Texas United States 75246
    22 Houston Texas United States 77030
    23 Salt Lake City Utah United States 84132
    24 Madison Wisconsin United States 53792
    25 Milwaukee Wisconsin United States 53215
    26 London Ontario Canada N6A 5A5
    27 Ottawa Ontario Canada K1Y 4W7
    28 Frankfurt Am Main Germany 60590
    29 Hannover Germany 30625
    30 Goeteborg Sweden 41345

    Sponsors and Collaborators

    • Hoffmann-La Roche

    Investigators

    • Study Director: Clinical Trials, Hoffmann-La Roche

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT00048165
    Other Study ID Numbers:
    • NR15880
    First Posted:
    Oct 25, 2002
    Last Update Posted:
    Jun 13, 2016
    Last Verified:
    May 1, 2016
    Additional relevant MeSH terms:
    Cyclosporine
    Mycophenolic Acid
    Methylprednisolone
    Cyclosporins
    Daclizumab

    Study Results

    Participant Flow

    Recruitment Details The study was conducted across 31 centers in four countries from 28 Aug 1999 to 19 Aug 2002.
    Pre-assignment Detail
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Period Title: Completed 6 Months Study
    STARTED 216 218
    COMPLETED 165 170
    NOT COMPLETED 51 48
    Period Title: Completed 6 Months Study
    STARTED 165 170
    COMPLETED 162 167
    NOT COMPLETED 3 3

    Baseline Characteristics

    Arm/Group Title Daclizumab Placebo Total
    Arm/Group Description Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an intravenous matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Total of all reporting groups
    Overall Participants 216 218 434
    Age (years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [years]
    52.4
    (11.75)
    53.1
    (11.89)
    52.8
    (11.81)
    Sex: Female, Male (Count of Participants)
    Female
    45
    20.8%
    41
    18.8%
    86
    19.8%
    Male
    171
    79.2%
    177
    81.2%
    348
    80.2%

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant
    Description The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months post-transplant (PT). Participants with acute rejection included participants with a biopsy histology of International Society of Heart and Lung Transplant (ISHLT) Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up.
    Time Frame Up to 6 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Number [participants]
    77
    35.6%
    104
    47.7%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Daclizumab, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.007
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter percent mean difference
    Estimated Value -12.0
    Confidence Interval (2-Sided) 95%
    -20.9 to -3.3
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    2. Secondary Outcome
    Title Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT
    Description The acute rejection episode was a composite end-point of acute rejection and treatment failure within 6 months. Participants with acute rejection included participants with a biopsy histology of ISHLT Grade IIIA, IIIB, or IV and participants with hemodynamic compromise (HDC) who were treated for acute rejection (whether or not a biopsy was done and regardless of the grade of the biopsy). Participants who had treatment failure included participants who died within 6 months of transplantation before experiencing acute rejection or who were re-transplanted within 6 months of the primary transplantation and who did not experience an acute rejection or who were lost to follow-up
    Time Frame Up to 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Number [participants]
    97
    44.9%
    116
    53.2%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Daclizumab, Placebo
    Comments
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.063
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Method of Estimation Estimation Parameter percent mean difference
    Estimated Value -8.6
    Confidence Interval (2-Sided) 95%
    -17.7 to 0.5
    Parameter Dispersion Type:
    Value:
    Estimation Comments
    3. Secondary Outcome
    Title Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT
    Description The number of participants with 0,1, 2, 3 or 4 episodes at 6 and 12 months PT were reported. An episode of acute rejection was defined according to the date of positive biopsy of Grade IIIA or worse or the date of start of treatment for HDC, whichever came first.
    Time Frame Within 6 months and 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Within 6 months, 0 episode
    139
    64.4%
    114
    52.3%
    Within 6 months, 1 episode
    63
    29.2%
    82
    37.6%
    Within 6 months, 2 episodes
    12
    5.6%
    19
    8.7%
    Within 6 months, 3 episodes
    2
    0.9%
    2
    0.9%
    Within 6 months, 4 episodes
    0
    0%
    1
    0.5%
    Within 12 months, 0 episode
    119
    55.1%
    102
    46.8%
    Within 12 months, 1 episode
    68
    31.5%
    90
    41.3%
    Within 12 months, 2 episodes
    23
    10.6%
    19
    8.7%
    Within 12 months, 3 episodes
    3
    1.4%
    5
    2.3%
    Within 12 months, 4 episodes
    3
    1.4%
    2
    0.9%
    4. Secondary Outcome
    Title Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT
    Description The survival of the graft and participants at 6,12 months and 3 years PT was reported
    Time Frame At 6 months, 12 months , 3 years PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Within 6 months
    16
    7.4%
    10
    4.6%
    Within 12 months
    21
    9.7%
    12
    5.5%
    Within 3 years
    NA
    NaN
    NA
    NaN
    5. Secondary Outcome
    Title Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT
    Description The number of participants with Worst International Society of Heart and Lung Transplant (ISHLT) grade within first 6 months and 12 months PT were reported. ISHLT is a standardized grading method to determine the acute cellular rejection on endomyocardial biopsy ; where 0= no rejection, IA= focal (perivascular or interstitial) infiltrate without necrosis, IB= diffuse but sparse infiltrate without necrosis, II=one focus only with aggressive infiltration and/or focal myocyte damage, IIIA=multifocal aggressive infiltrates and/or myocyte damage, IIIB= diffuse inflammatory process with necrosis, IV= diffuse aggressive polymorphous and/or infiltrate and/or edema and/or hemorrhage and/or vasculitis, with necrosis
    Time Frame Within 6 months and 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Within 6 months, Grade 0
    9
    4.2%
    5
    2.3%
    Within 6 months, Grade IA
    64
    29.6%
    51
    23.4%
    Within 6 months, Grade IB
    26
    12%
    28
    12.8%
    Within 6 months, Grade II
    55
    25.5%
    38
    17.4%
    Within 6 months, Grade IIIA
    48
    22.2%
    74
    33.9%
    Within 6 months, Grade IIIB
    8
    3.7%
    15
    6.9%
    Within 6 months, Grade IV
    1
    0.5%
    1
    0.5%
    Within 12 months, Grade 0
    7
    3.2%
    4
    1.8%
    Within 12 months, Grade IA
    56
    25.9%
    39
    17.9%
    Within 12 months, Grade IB
    22
    10.2%
    21
    9.6%
    Within 12 months, Grade II
    51
    23.6%
    47
    21.6%
    Within 12 months, Grade IIIA
    63
    29.2%
    85
    39%
    Within 12 months, Grade IIIB
    11
    5.1%
    15
    6.9%
    Within 12 months, Grade IV
    1
    0.5%
    1
    0.5%
    Statistical Analysis 1
    Statistical Analysis Overview Comparison Group Selection Daclizumab, Placebo
    Comments Comparison of Daclizumab and Placebo for 6 months were presented
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0005
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    Statistical Analysis 2
    Statistical Analysis Overview Comparison Group Selection Daclizumab, Placebo
    Comments Comparison of Daclizumab and Placebo for 12 months were presented
    Type of Statistical Test Superiority or Other
    Comments
    Statistical Test of Hypothesis p-Value 0.0008
    Comments
    Method Cochran-Mantel-Haenszel
    Comments
    6. Secondary Outcome
    Title Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT
    Description The median time to first acute rejection episode within first 6 months and 12 months PT was reported.
    Time Frame Within 6 months and 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not. The number of participants analyzed for the specified timepoints are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 97 116
    Within 6 months (n= 77, 104)
    61
    21
    Within 12 months (n=97, 116)
    96
    26
    7. Secondary Outcome
    Title Number of Participants Using Monomurab Cluster of Differentiation 3, Orthoclone Polyclonal Antithymocyte Globulin or Antilymphocyte Globulin in the First 6 Months and 12 Months PT
    Description The number of participants who received monomurab Cluster of differentiation 3, orthoclone, polyclonal antithymocyte globulin or antilymphocyte globulin for treatment of biopsy proven rejection or HDC within 6 and 12 months PT were reported.
    Time Frame Within 6 months and 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 218
    Within 6 months
    17
    7.9%
    19
    8.7%
    Within 12 months
    23
    10.6%
    21
    9.6%
    8. Secondary Outcome
    Title Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT
    Description The maintenance doses of mycophenolate mofetil (1.5g twice a day daily), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg oral [PO]/nasogastric [NG] within 72 hours post-operative]), and cumulative dose of corticosteroids (500-1000 mg IV methylprednisolone pre-operative switched to oral at 0.5-1 mg/kg/day. Tapered to 0.2 mg/kg/d by Day 28, 0.1-0.15 mg/kg/day from Days 36 to 90, and 0.1-0.15 mg/kg/day from Days 120 to 180)at 6 and 12 months PT were reported. Maintenance dose was calculated as total dose per day summed over all days that a participant was administered drug within the specified time interval, divided by number of days that a participant took drug within that time interval.
    Time Frame Within 6 months and 12 months PT

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not. The number of participants analyzed for the specified timepoints are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 203 206
    MMF dose, 6 months PT (n=193, 201)
    2522.2
    (791)
    2450
    (748.9)
    MMF dose,12 months PT (n=188, 194)
    2394.1
    (808)
    2380.1
    (779.2)
    IV Cyclosporine dose, 6 months PT (n=2, 1)
    86.11
    (102.7)
    38.1
    (NA)
    IV Cyclosporine dose, 12 months PT (n=4, 2)
    93.5
    (84.3)
    46.7
    (18)
    PO/NG Cyclosporine dose, 6 months PT (n=184, 182)
    321.9
    (106.6)
    331.1
    (121.7)
    PO/NG Cyclosporine dose, 12 months PT (n=170, 170)
    294.7
    (93.8)
    305.7
    (116.6)
    Cumulative corticosteroids,6 months PT(n=203, 206)
    848.1
    (402)
    955.4
    (442.8)
    Cumulative corticosteroids,12 months PT(n=195,200)
    1199.6
    (771.8)
    1288.9
    (796.1)
    9. Secondary Outcome
    Title Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides)
    Description Lipid profile included total cholesterol, low density lipoproteins (LDL), high density lipoproteins (HDL), and triglycerides (all total cholesterol, LDL, HDL, and triglycerides with unit milligram per decilitre [mg/dL]), were reported. The median change from baseline (Day -2) in lipid profile values at 3 months and 6 months was reported.
    Time Frame From Baseline (Day -2) to 3 months and 6 months

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not. The number of participants analyzed for the specified parameters are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 126 130
    Total cholesterol, change at 3 months (n=119,119)
    0.65
    0.91
    Total cholesterol, change at 6 months (n=126,130)
    0.28
    0.61
    LDL, Change at 3 months (n=92,89)
    0.25
    0.34
    LDL, Change at 6 months (n=91,99)
    0.03
    0.21
    HDL, change at 3 months (n=97, 101)
    0.34
    0.31
    HDL, change at 6 months (n=102,112)
    0.23
    0.20
    Triglycerides,change at 3 months (n=104,108)
    0.26
    0.46
    Triglycerides,change at 6 months (n=109,117)
    0.20
    0.44
    LDL/HDL ratio,change at 3 months (n=91,89)
    -0.44
    -0.12
    LDL/HDL ratio,change at 6 months (n=91, 99)
    -0.50
    -0.14
    10. Secondary Outcome
    Title Median Change From Baseline for LDL/HDL Ratio
    Description
    Time Frame From Baseline (Day -2) to 3 months, and 6 months

    Outcome Measure Data

    Analysis Population Description
    The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 91 99
    LDL/HDL ratio,change at 3 months (n=91,89)
    -0.44
    -0.12
    LDL/HDL ratio,change at 6 months (n=91, 99)
    -0.50
    -0.14
    11. Secondary Outcome
    Title Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters
    Description A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Hematology included hemoglobin, hematocrit, white blood cell count (WBC) with differential (including granulocytes or neutrophils, basophils, eosinophils, monocytes, lymphocytes), platelets, and erythrocyte count
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc). The number of participants analyzed for the specified parameters are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 210 204
    Hematocrit-high (n=210, 203)
    0
    0%
    0
    0%
    Hematocrit-low (n=210, 203)
    116
    53.7%
    117
    53.7%
    Hemoglobin-high (n=210, 204)
    0
    0%
    0
    0%
    Hemoglobin-low (n=210, 204)
    107
    49.5%
    112
    51.4%
    Platelets-high (n=210, 203)
    2
    0.9%
    1
    0.5%
    Platelets-low (n=210, 203)
    30
    13.9%
    22
    10.1%
    RBC-high (n=209, 203)
    1
    0.5%
    2
    0.9%
    RBC-low (n=209, 203)
    116
    53.7%
    106
    48.6%
    Basophils-high (n=199, 195)
    4
    1.9%
    4
    1.8%
    Eosinophils-high (n=199, 195)
    0
    0%
    0
    0%
    Lymphocytes-high (n=199, 198)
    2
    0.9%
    2
    0.9%
    Lymphocytes-low (n=199, 198)
    157
    72.7%
    157
    72%
    Monocytes-high (n=199, 198)
    5
    2.3%
    6
    2.8%
    Monocytes-low (n=199, 198)
    14
    6.5%
    20
    9.2%
    Neutrophils-low (n= 199, 198)
    33
    15.3%
    33
    15.1%
    WBC-high (n=207, 201)
    61
    28.2%
    57
    26.1%
    WBC-low (n=207, 201)
    43
    19.9%
    29
    13.3%
    12. Secondary Outcome
    Title Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters
    Description A marked reference range was predefined by Roche. The marked reference range is broader than the standard reference range. Values falling outside the marked reference range (low or high) that also represent a defined change from Baseline were considered marked laboratory abnormalities (i.e. potentially clinically relevant). Biochemistry included blood urea nitrogen, creatinine, serum glutamic oxalacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), gamma-glutamyl transferase (GGT), phosphorous, total bilirubin, direct bilirubin, total protein, albumin, glucose, alkaline phosphatase, low density lipoprotein (LDH), uric acid, carbon dioxide, magnesium, sodium, potassium, chloride, calcium, LDL, HDL, total cholesterol, and triglycerides.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc). The number of participants analyzed for the specified parameters are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 210 204
    SGPT-high (n=200, 200)
    48
    22.2%
    45
    20.6%
    ALP-high (n=201, 200)
    15
    6.9%
    7
    3.2%
    SGOT-high (n=201, 200)
    22
    10.2%
    25
    11.5%
    GGT-high (n=180, 175)
    90
    41.7%
    74
    33.9%
    LDH-high (n=194, 191)
    53
    24.5%
    54
    24.8%
    Total bilirubin-high (n=201, 200)
    28
    13%
    20
    9.2%
    BUN-high (n= 210, 200)
    93
    43.1%
    95
    43.6%
    Creatinine-high (n=211, 203)
    66
    30.6%
    64
    29.4%
    Albumin-low (n=198,197)
    47
    21.8%
    50
    22.9%
    Total protein-high (n=195,196)
    5
    2.3%
    0
    0%
    Total protein-low(n=195,196)
    85
    39.4%
    79
    36.2%
    Cholesterol-high (n=174, 174)
    3
    1.4%
    4
    1.8%
    Triglycerides-high (n=164, 164)
    35
    16.2%
    30
    13.8%
    Carbondioxide-high (n=206, 197)
    27
    12.5%
    21
    9.6%
    Carbondioxide-low (n=206, 197)
    12
    5.6%
    5
    2.3%
    Chloride-high (n=211, 203)
    1
    0.5%
    3
    1.4%
    Chloride-low (n=211, 203)
    42
    19.4%
    36
    16.5%
    Potassium-high (n=211, 204)
    7
    3.2%
    7
    3.2%
    Potassium-low (n=211, 204)
    4
    1.9%
    2
    0.9%
    Sodium-high (n=211, 203)
    2
    0.9%
    1
    0.5%
    Sodium-low (n=211, 203)
    8
    3.7%
    11
    5%
    Calcium-low (n=207, 201)
    39
    18.1%
    44
    20.2%
    Glucose fasting-high (n=210, 203)
    28
    13%
    27
    12.4%
    Glucose fasting-low (n=210, 203)
    3
    1.4%
    3
    1.4%
    Phosphate-high (n=199, 194)
    54
    25%
    48
    22%
    Phosphate-low (n=199,194)
    32
    14.8%
    26
    11.9%
    Uric acid high (n=191, 188)
    23
    10.6%
    20
    9.2%
    13. Secondary Outcome
    Title Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal
    Description An adverse event (AE) is any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. An AE can therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Pre-existing conditions which worsened during this study were reported as AEs. A serious adverse event (SAE) is any untoward medical occurrence that at any dose results in death, are life threatening, requires hospitalization or prolongation of hospitalization or results in disability/incapacity, and congenital anomaly/birth defect.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc).
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 207
    Any AEs
    214
    99.1%
    207
    95%
    Any SAE's
    108
    50%
    102
    46.8%
    Any AEs leading to premature discontinuation
    14
    6.5%
    11
    5%
    14. Secondary Outcome
    Title Number of Participants With Malignancies and Opportunistic Infections
    Description The opportunistic infections included infections with Cytomegalovirus, Aspergillus, Candida, Pneumocystis, Cryptococcus, Listeria, Herpes simplex, Herpes zoster. For malignancy, participants with any type of malignancy whose date of onset or diagnosis was after randomization was reported.
    Time Frame Up to 12 months

    Outcome Measure Data

    Analysis Population Description
    Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc).
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous (IV) dose of daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID]), cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV peri-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    Measure Participants 216 207
    Participants with malignancies
    11
    5.1%
    11
    5%
    Participants with opportunistic infections
    71
    32.9%
    80
    36.7%

    Adverse Events

    Time Frame Up to 12 months
    Adverse Event Reporting Description Safety population included all participants who received at least one dose of study drug (daclizumab or placebo) or commercially available daclizumab and have at least one post-baseline safety assessment (eg. any laboratory data, adverse event, etc). The number of participants analyzed for the specified parameters are denoted by 'n'.
    Arm/Group Title Daclizumab Placebo
    Arm/Group Description Eligible participants were administered an intravenous daclizumab (1 milligrams per kilogram [mg/kg]) on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days. Eligible participants were administered an IV dose of matching placebo on Days 1, 8, 22, 36, and 50, along with mycophenolate mofetil (one dose of 1.5 mg twice daily [BID], cyclosporine (1-4 mg/kg IV or 2-6 mg/kg orally/nasogastric), and corticosteroid (methylprednisolone, 500-1000 mg IV pre-operative switch to oral at 0.5-1 mg/kg/day followed by tapering). Participants received mycophenolate mofetil, cyclosporine, and corticosteroid up to 365 days.
    All Cause Mortality
    Daclizumab Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Daclizumab Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 108/216 (50%) 102/207 (49.3%)
    Blood and lymphatic system disorders
    Coagulation disorder nos 1/216 (0.5%) 0/207 (0%)
    Leukopenia nos 1/216 (0.5%) 3/207 (1.4%)
    Neutropenia 1/216 (0.5%) 2/207 (1%)
    Thrombocytopenia 1/216 (0.5%) 0/207 (0%)
    Thrombotic thrombocytopenic purpura 0/216 (0%) 1/207 (0.5%)
    Cardiac disorders
    Arrhythmia nos 1/216 (0.5%) 1/207 (0.5%)
    Atrial fibrillation 4/216 (1.9%) 2/207 (1%)
    Atrial flutter 2/216 (0.9%) 5/207 (2.4%)
    Atrial tachycardia 1/216 (0.5%) 2/207 (1%)
    Atrioventricular block complete 1/216 (0.5%) 0/207 (0%)
    Atrioventricular block nos 1/216 (0.5%) 0/207 (0%)
    Bradycardia nos 1/216 (0.5%) 1/207 (0.5%)
    Cardiac arrest 6/216 (2.8%) 7/207 (3.4%)
    Cardiac failure congestive 1/216 (0.5%) 0/207 (0%)
    Cardiac failure nos 0/216 (0%) 1/207 (0.5%)
    Cardiac tamponade 3/216 (1.4%) 3/207 (1.4%)
    Cardiogenic shock 2/216 (0.9%) 0/207 (0%)
    Coronary artery disease nos 0/216 (0%) 1/207 (0.5%)
    Endocarditis nos 1/216 (0.5%) 0/207 (0%)
    Palpitations 1/216 (0.5%) 0/207 (0%)
    Pericardial effusion 6/216 (2.8%) 4/207 (1.9%)
    Post myocardial infarction syndrome 0/216 (0%) 1/207 (0.5%)
    Pulmonary oedema nos 0/216 (0%) 2/207 (1%)
    Right ventricular failure 2/216 (0.9%) 1/207 (0.5%)
    Supraventricular tachycardia 1/216 (0.5%) 1/207 (0.5%)
    Tachycardia nos 0/216 (0%) 1/207 (0.5%)
    Tricuspid valve incompetence 0/216 (0%) 1/207 (0.5%)
    Ventricular arrhythmia nos 1/216 (0.5%) 0/207 (0%)
    Ventricular fibrillation 0/216 (0%) 1/207 (0.5%)
    Ventricular hypokinesia 1/216 (0.5%) 0/207 (0%)
    Ventricular tachycardia 1/216 (0.5%) 0/207 (0%)
    Gastrointestinal disorders
    Antibiotic associated colitis 0/216 (0%) 1/207 (0.5%)
    Ascites 1/216 (0.5%) 0/207 (0%)
    Caecum perforation 0/216 (0%) 1/207 (0.5%)
    Colonic perforation 2/216 (0.9%) 0/207 (0%)
    Duodenal ulcer perforation 0/216 (0%) 1/207 (0.5%)
    Food poisoning nos 1/216 (0.5%) 0/207 (0%)
    Gastric ulcer haemorrhage 0/216 (0%) 1/207 (0.5%)
    Gastritis nos 0/216 (0%) 1/207 (0.5%)
    Gastrointestinal haemorrhage nos 0/216 (0%) 1/207 (0.5%)
    Ileus paralytic 1/216 (0.5%) 0/207 (0%)
    Intra-abdominal haemorrhage nos 1/216 (0.5%) 0/207 (0%)
    Irritable bowel syndrome 1/216 (0.5%) 0/207 (0%)
    Mesenteric occlusion 0/216 (0%) 1/207 (0.5%)
    Oesophageal perforation 0/216 (0%) 1/207 (0.5%)
    Small intestinal perforation nos 0/216 (0%) 1/207 (0.5%)
    Toxic dilatation of colon 1/216 (0.5%) 0/207 (0%)
    Large intestinal ulcer 0/216 (0%) 1/207 (0.5%)
    General disorders
    Asthenia 0/216 (0%) 1/207 (0.5%)
    Debility 1/216 (0.5%) 1/207 (0.5%)
    Heparin-induced thrombocytopenia nos 0/216 (0%) 1/207 (0.5%)
    Malaise 0/216 (0%) 1/207 (0.5%)
    Multi-organ failure 1/216 (0.5%) 4/207 (1.9%)
    Pyrexia 4/216 (1.9%) 3/207 (1.4%)
    Sudden cardiac death 0/216 (0%) 1/207 (0.5%)
    Weakness 0/216 (0%) 1/207 (0.5%)
    Hepatobiliary disorders
    Cholelithiasis 1/216 (0.5%) 0/207 (0%)
    Immune system disorders
    Humoral immune defect 1/216 (0.5%) 0/207 (0%)
    Infections and infestations
    Abscess nos 2/216 (0.9%) 0/207 (0%)
    Cellulitis 2/216 (0.9%) 0/207 (0%)
    Cellulitis staphylococcal 0/216 (0%) 1/207 (0.5%)
    Clostridial infection nos 0/216 (0%) 1/207 (0.5%)
    Empyema nos 1/216 (0.5%) 0/207 (0%)
    Gastroenteritis nos 1/216 (0.5%) 1/207 (0.5%)
    Gastroenteritis viral nos 1/216 (0.5%) 0/207 (0%)
    Influenza 0/216 (0%) 1/207 (0.5%)
    Injection site infection 2/216 (0.9%) 0/207 (0%)
    Interstitial pneumonia 0/216 (0%) 1/207 (0.5%)
    Pharyngitis streptococcal 1/216 (0.5%) 0/207 (0%)
    Pleural infection nos 1/216 (0.5%) 0/207 (0%)
    Pneumonia gram-negative bacterial nos 1/216 (0.5%) 0/207 (0%)
    Pneumonia nos 6/216 (2.8%) 5/207 (2.4%)
    Purulent pericarditis 1/216 (0.5%) 0/207 (0%)
    Sepsis nos 7/216 (3.2%) 4/207 (1.9%)
    Septic shock 2/216 (0.9%) 0/207 (0%)
    Septicaemia staphylococcal 0/216 (0%) 1/207 (0.5%)
    Septicaemia streptococcal 0/216 (0%) 1/207 (0.5%)
    Upper respiratory tract infection nos 2/216 (0.9%) 0/207 (0%)
    Urinary tract infection nos 0/216 (0%) 2/207 (1%)
    Viral infection nos 2/216 (0.9%) 1/207 (0.5%)
    Wound infection nec 6/216 (2.8%) 2/207 (1%)
    Injury, poisoning and procedural complications
    Ankle fracture 0/216 (0%) 1/207 (0.5%)
    Aortic injury 2/216 (0.9%) 0/207 (0%)
    Brain herniation 0/216 (0%) 1/207 (0.5%)
    Corneal abrasion 1/216 (0.5%) 0/207 (0%)
    Haemothorax 1/216 (0.5%) 0/207 (0%)
    Post procedural drainage 1/216 (0.5%) 0/207 (0%)
    Post procedural haemorrhage 2/216 (0.9%) 0/207 (0%)
    Postoperative haematoma 0/216 (0%) 1/207 (0.5%)
    Seroma 0/216 (0%) 1/207 (0.5%)
    Spinal compression fracture 1/216 (0.5%) 1/207 (0.5%)
    Therapeutic agent poisoning 0/216 (0%) 1/207 (0.5%)
    Traumatic chest injury nos 0/216 (0%) 1/207 (0.5%)
    Upper limb fracture nos 0/216 (0%) 1/207 (0.5%)
    Wound dehiscence 2/216 (0.9%) 2/207 (1%)
    Investigations
    Liver function tests nos abnormal 1/216 (0.5%) 0/207 (0%)
    Weight increased 0/216 (0%) 1/207 (0.5%)
    Metabolism and nutrition disorders
    Dehydration 1/216 (0.5%) 1/207 (0.5%)
    Diabetes mellitus nos 0/216 (0%) 2/207 (1%)
    Fluid overload 4/216 (1.9%) 3/207 (1.4%)
    Gout 1/216 (0.5%) 1/207 (0.5%)
    Hyperglycemia nos 1/216 (0.5%) 0/207 (0%)
    Hypovolaemia 0/216 (0%) 1/207 (0.5%)
    Musculoskeletal and connective tissue disorders
    Muscle necrosis 1/216 (0.5%) 0/207 (0%)
    Myopathy steroid 1/216 (0.5%) 1/207 (0.5%)
    Rhabdomyolysis 1/216 (0.5%) 1/207 (0.5%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Adenoma benign nos 0/216 (0%) 1/207 (0.5%)
    Basal cell carcinoma 4/216 (1.9%) 3/207 (1.4%)
    Precancerous skin lesion 1/216 (0.5%) 0/207 (0%)
    Squamous cell carcinoma 1/216 (0.5%) 1/207 (0.5%)
    Squamous cell carcinoma of skin 1/216 (0.5%) 0/207 (0%)
    Nervous system disorders
    Anoxic encephalopathy 2/216 (0.9%) 1/207 (0.5%)
    Compartment syndrome 0/216 (0%) 1/207 (0.5%)
    Convulsions nos 4/216 (1.9%) 1/207 (0.5%)
    Encephalopathy nos 2/216 (0.9%) 0/207 (0%)
    Grand mal convulsion 0/216 (0%) 2/207 (1%)
    Headache nos 1/216 (0.5%) 0/207 (0%)
    Intracranial haemorrhage nos 2/216 (0.9%) 0/207 (0%)
    Migraine nos 1/216 (0.5%) 1/207 (0.5%)
    Syncope 2/216 (0.9%) 2/207 (1%)
    Transient ischaemic attack 1/216 (0.5%) 0/207 (0%)
    Tremor 0/216 (0%) 1/207 (0.5%)
    Psychiatric disorders
    Delirium tremens 0/216 (0%) 1/207 (0.5%)
    Depression nos 0/216 (0%) 1/207 (0.5%)
    Mania 0/216 (0%) 2/207 (1%)
    Mental status changes 0/216 (0%) 1/207 (0.5%)
    Renal and urinary disorders
    Calculus renal nos 1/216 (0.5%) 0/207 (0%)
    Calculus ureteric 1/216 (0.5%) 0/207 (0%)
    Dysuria 0/216 (0%) 1/207 (0.5%)
    Hydronephrosis 1/216 (0.5%) 0/207 (0%)
    Loin pain 0/216 (0%) 1/207 (0.5%)
    Renal artery stenosis 1/216 (0.5%) 0/207 (0%)
    Renal failure acute 2/216 (0.9%) 8/207 (3.9%)
    Renal failure nos 2/216 (0.9%) 3/207 (1.4%)
    Renal impairment nos 2/216 (0.9%) 3/207 (1.4%)
    Renal tubular necrosis 1/216 (0.5%) 2/207 (1%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/216 (0%) 1/207 (0.5%)
    Mediastinal haematoma 1/216 (0.5%) 0/207 (0%)
    Mediastinitis 2/216 (0.9%) 2/207 (1%)
    Non-cardiogenic pulmonary oedema 0/216 (0%) 1/207 (0.5%)
    Pleural effusion 5/216 (2.3%) 4/207 (1.9%)
    Pneumothorax nos 2/216 (0.9%) 4/207 (1.9%)
    Respiratory distress 2/216 (0.9%) 1/207 (0.5%)
    Respiratory failure (excl neonatal) 3/216 (1.4%) 4/207 (1.9%)
    Diaphragmatic paralysis 0/216 (0%) 1/207 (0.5%)
    Excessive bronchial secretion 1/216 (0.5%) 0/207 (0%)
    Vascular disorders
    Aortic aneurysm rupture 0/216 (0%) 1/207 (0.5%)
    Arterial haemorrhage nos 1/216 (0.5%) 0/207 (0%)
    Cerebellar infarction 0/216 (0%) 1/207 (0.5%)
    Cerebral haemorrhage 1/216 (0.5%) 0/207 (0%)
    Cerebral infarction 1/216 (0.5%) 2/207 (1%)
    Cerebrovascular accident nos 0/216 (0%) 1/207 (0.5%)
    Deep venous thrombosis nos 1/216 (0.5%) 2/207 (1%)
    Femoral artery occlusion 0/216 (0%) 1/207 (0.5%)
    Haemorrhage nos 0/216 (0%) 1/207 (0.5%)
    Hypertension nos 0/216 (0%) 1/207 (0.5%)
    Hypotension nos 0/216 (0%) 2/207 (1%)
    Jugular vein thrombosis 1/216 (0.5%) 0/207 (0%)
    Lymphocele 0/216 (0%) 2/207 (1%)
    Lymphorrhoea 0/216 (0%) 1/207 (0.5%)
    Orthostatic hypotension 0/216 (0%) 1/207 (0.5%)
    Peripheral vascular disorder nos 1/216 (0.5%) 0/207 (0%)
    Pulmonary embolism 1/216 (0.5%) 0/207 (0%)
    Pulmonary hypertension nos 2/216 (0.9%) 2/207 (1%)
    Shock 0/216 (0%) 1/207 (0.5%)
    Venous thrombosis deep limb 1/216 (0.5%) 2/207 (1%)
    Other (Not Including Serious) Adverse Events
    Daclizumab Placebo
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 210/216 (97.2%) 204/207 (98.6%)
    Blood and lymphatic system disorders
    Anaemia nos 64/216 (29.6%) 52/207 (25.1%)
    Leukocytosis 15/216 (6.9%) 16/207 (7.7%)
    Leukopenia nos 32/216 (14.8%) 22/207 (10.6%)
    Neutropenia 17/216 (7.9%) 11/207 (5.3%)
    Thrombocytopenia 22/216 (10.2%) 26/207 (12.6%)
    Cardiac disorders
    Arrhythmia nos 10/216 (4.6%) 12/207 (5.8%)
    Atrial fibrillation 22/216 (10.2%) 20/207 (9.7%)
    Bradycardia nos 16/216 (7.4%) 17/207 (8.2%)
    Nodal arrhythmia 19/216 (8.8%) 17/207 (8.2%)
    Pericardial effusion 34/216 (15.7%) 35/207 (16.9%)
    Pericardial rub 10/216 (4.6%) 12/207 (5.8%)
    Right ventricular failure 13/216 (6%) 13/207 (6.3%)
    Supraventricular tachycardia 17/216 (7.9%) 11/207 (5.3%)
    Tachycardia nos 10/216 (4.6%) 11/207 (5.3%)
    Tricuspid valve incompetence 18/216 (8.3%) 15/207 (7.2%)
    Ventricular hypokinesia 11/216 (5.1%) 14/207 (6.8%)
    Ventricular tachycardia 11/216 (5.1%) 10/207 (4.8%)
    Gastrointestinal disorders
    Abdominal distension 13/216 (6%) 9/207 (4.3%)
    Abdominal pain nos 17/216 (7.9%) 21/207 (10.1%)
    Abdominal pain upper 4/216 (1.9%) 12/207 (5.8%)
    Constipation 81/216 (37.5%) 80/207 (38.6%)
    Diarrhoea nos 51/216 (23.6%) 42/207 (20.3%)
    Dyspepsia 16/216 (7.4%) 17/207 (8.2%)
    Gastrointestinal upset 12/216 (5.6%) 5/207 (2.4%)
    Hiccups 11/216 (5.1%) 12/207 (5.8%)
    Nausea 88/216 (40.7%) 101/207 (48.8%)
    Pharyngolaryngeal pain 14/216 (6.5%) 10/207 (4.8%)
    Vomiting nos 42/216 (19.4%) 38/207 (18.4%)
    General disorders
    Chest pain 17/216 (7.9%) 22/207 (10.6%)
    Fatigue 36/216 (16.7%) 43/207 (20.8%)
    Oedema lower limb 58/216 (26.9%) 60/207 (29%)
    Oedema nos 36/216 (16.7%) 35/207 (16.9%)
    Oedema peripheral 18/216 (8.3%) 19/207 (9.2%)
    Pain nos 18/216 (8.3%) 13/207 (6.3%)
    Pyrexia 26/216 (12%) 22/207 (10.6%)
    Rigors 15/216 (6.9%) 10/207 (4.8%)
    Weakness 30/216 (13.9%) 24/207 (11.6%)
    Infections and infestations
    Bronchitis nos 7/216 (3.2%) 12/207 (5.8%)
    Nasopharyngitis 16/216 (7.4%) 10/207 (4.8%)
    Pneumonia nos 12/216 (5.6%) 6/207 (2.9%)
    Upper respiratory tract infection nos 21/216 (9.7%) 9/207 (4.3%)
    Urinary tract infection nos 18/216 (8.3%) 12/207 (5.8%)
    Injury, poisoning and procedural complications
    Post procedural pain 106/216 (49.1%) 105/207 (50.7%)
    Wound secretion 15/216 (6.9%) 12/207 (5.8%)
    Investigations
    Liver function tests nos abnormal 12/216 (5.6%) 12/207 (5.8%)
    Weight increased 14/216 (6.5%) 7/207 (3.4%)
    Metabolism and nutrition disorders
    Diabetes mellitus nos 7/216 (3.2%) 12/207 (5.8%)
    Gout 13/216 (6%) 18/207 (8.7%)
    Hyperglycaemia nos 58/216 (26.9%) 72/207 (34.8%)
    Hyperkalaemia 29/216 (13.4%) 22/207 (10.6%)
    Hyperlipidaemia nos 11/216 (5.1%) 9/207 (4.3%)
    Hypervolaemia 14/216 (6.5%) 8/207 (3.9%)
    Hypoglycaemia nos 15/216 (6.9%) 8/207 (3.9%)
    Hypokalaemia 17/216 (7.9%) 16/207 (7.7%)
    Hypomagnesaemia 14/216 (6.5%) 17/207 (8.2%)
    Hyponatraemia 5/216 (2.3%) 12/207 (5.8%)
    Metabolic acidosis nos 11/216 (5.1%) 12/207 (5.8%)
    Fluid overload 43/216 (19.9%) 56/207 (27.1%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 29/216 (13.4%) 23/207 (11.1%)
    Back pain 39/216 (18.1%) 33/207 (15.9%)
    Muscle cramps 21/216 (9.7%) 31/207 (15%)
    Myalgia 11/216 (5.1%) 11/207 (5.3%)
    Pain in limb 18/216 (8.3%) 20/207 (9.7%)
    Peripheral swelling 9/216 (4.2%) 16/207 (7.7%)
    Nervous system disorders
    Dizziness (excl vertigo) 42/216 (19.4%) 32/207 (15.5%)
    Headache nos 64/216 (29.6%) 58/207 (28%)
    Hypoaesthesia 14/216 (6.5%) 13/207 (6.3%)
    Paraesthesia 14/216 (6.5%) 20/207 (9.7%)
    Tremor 62/216 (28.7%) 67/207 (32.4%)
    Psychiatric disorders
    Agitation 23/216 (10.6%) 12/207 (5.8%)
    Anxiety nec 28/216 (13%) 42/207 (20.3%)
    Confusion 15/216 (6.9%) 11/207 (5.3%)
    Depression nos 22/216 (10.2%) 18/207 (8.7%)
    Insomnia 82/216 (38%) 81/207 (39.1%)
    Renal and urinary disorders
    Dysuria 9/216 (4.2%) 16/207 (7.7%)
    Oliguria 26/216 (12%) 28/207 (13.5%)
    Renal impairment nos 50/216 (23.1%) 43/207 (20.8%)
    Respiratory, thoracic and mediastinal disorders
    Atelectasis 22/216 (10.2%) 22/207 (10.6%)
    Breath sounds decreased 3/216 (1.4%) 13/207 (6.3%)
    Cough 16/216 (7.4%) 24/207 (11.6%)
    Dyspnoea nos 27/216 (12.5%) 24/207 (11.6%)
    Pleural effusion 55/216 (25.5%) 41/207 (19.8%)
    Pneumothorax nos 13/216 (6%) 15/207 (7.2%)
    Productive cough 4/216 (1.9%) 13/207 (6.3%)
    Skin and subcutaneous tissue disorders
    Acne nos 13/216 (6%) 10/207 (4.8%)
    Pressure sore 12/216 (5.6%) 12/207 (5.8%)
    Rash nos 17/216 (7.9%) 20/207 (9.7%)
    Vascular disorders
    Hypertension nos 119/216 (55.1%) 131/207 (63.3%)
    Hypotension nos 41/216 (19%) 36/207 (17.4%)
    Pulmonary hypertension nos 22/216 (10.2%) 12/207 (5.8%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The Study being conducted under this Agreement is part of the Overall Study. Investigator is free to publish in reputable journals or to present at professional conferences the results of the Study, but only after the first publication or presentation that involves the Overall Study. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsor's intellectual property rights.

    Results Point of Contact

    Name/Title Roche Trial Information Hotline
    Organization F. Hoffmann-La Roche AG
    Phone +41 616878333
    Email global.trial_information@roche.com
    Responsible Party:
    Hoffmann-La Roche
    ClinicalTrials.gov Identifier:
    NCT00048165
    Other Study ID Numbers:
    • NR15880
    First Posted:
    Oct 25, 2002
    Last Update Posted:
    Jun 13, 2016
    Last Verified:
    May 1, 2016