Heart Transplantation
Conditions
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.
Interventions
DRUGDaclizumab
Daclizumab will be administered as 1 mg/kg IV within 12 hours post-op (Day 1), and Days 8, 22, 36 and 50.
DRUGMethylprednisolone
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).
DRUGMycophenolate mofetil
Mycophenolate mofetil will be administered as 1.5 grams bid begun post-op, either IV or orally as required up to 365 days.
DRUGPlacebo
Matching placebo will be administered on Days 1, 8, 22, 36, and 50.
DRUGcyclosporine
Cyclosporine will be administered as 1-4 mg/kg IV or 2-6 mg/kg orally up to 365 days.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE
Eligibility
Sex/Gender
ALL
Age
13 Years to No maximum
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/mm\^3, platelets =\<50,000/mm\^3 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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 |
| 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 |
| 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. |
| 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. |
| 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. |
| 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 |
| Median Change From Baseline for LDL/HDL Ratio | From Baseline (Day -2) to 3 months, and 6 months | — |
| 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 |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
Canada, Germany, Sweden, United States
Participant flow
Recruitment details
The study was conducted across 31 centers in four countries from 28 Aug 1999 to 19 Aug 2002.
Participants by arm
| Arm | Count |
|---|---|
| Daclizumab 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. | 216 |
| Placebo 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. | 218 |
| Total | 434 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Completed 12 Months Study | Administration/Other | 0 | 2 |
| Completed 12 Months Study | Death | 2 | 1 |
| Completed 12 Months Study | Did not co-operate/Withdrew | 1 | 0 |
| Completed 6 Months Study | Abnormality of laboratory test | 1 | 0 |
| Completed 6 Months Study | Administration/Other | 8 | 8 |
| Completed 6 Months Study | Adverse event/intermittent illness | 14 | 11 |
| Completed 6 Months Study | Death | 12 | 6 |
| Completed 6 Months Study | Did not receive study drug | 6 | 6 |
| Completed 6 Months Study | Insufficient therapy | 1 | 4 |
| Completed 6 Months Study | Other violation | 4 | 6 |
| Completed 6 Months Study | Refused treatment | 5 | 5 |
| Completed 6 Months Study | Violation criteria | 0 | 2 |
Baseline characteristics
| Characteristic | Daclizumab | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 52.4 years STANDARD_DEVIATION 11.75 | 53.1 years STANDARD_DEVIATION 11.89 | 52.8 years STANDARD_DEVIATION 11.81 |
| Sex: Female, Male Female | 45 Participants | 41 Participants | 86 Participants |
| Sex: Female, Male Male | 171 Participants | 177 Participants | 348 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 210 / 216 | 204 / 207 |
| serious Total, serious adverse events | 108 / 216 | 102 / 207 |
Outcome results
Primary
Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant
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
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclizumab | Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant | 77 participants |
| Placebo | Number of Participants Who Developed Acute Rejection Episode Within 6 Months Post-Transplant | 104 participants |
p-value: 0.00795% CI: [-20.9, -3.3]Cochran-Mantel-Haenszel
Secondary
Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 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.
Time frame: Within 6 months and 12 months PT
Population: 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 | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | MMF dose, 6 months PT (n=193, 201) | 2522.2 mg | Standard Deviation 791 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | MMF dose,12 months PT (n=188, 194) | 2394.1 mg | Standard Deviation 808 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | IV Cyclosporine dose, 6 months PT (n=2, 1) | 86.11 mg | Standard Deviation 102.7 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | IV Cyclosporine dose, 12 months PT (n=4, 2) | 93.5 mg | Standard Deviation 84.3 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | PO/NG Cyclosporine dose, 6 months PT (n=184, 182) | 321.9 mg | Standard Deviation 106.6 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | PO/NG Cyclosporine dose, 12 months PT (n=170, 170) | 294.7 mg | Standard Deviation 93.8 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | Cumulative corticosteroids,6 months PT(n=203, 206) | 848.1 mg | Standard Deviation 402 |
| Daclizumab | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | Cumulative corticosteroids,12 months PT(n=195,200) | 1199.6 mg | Standard Deviation 771.8 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | Cumulative corticosteroids,12 months PT(n=195,200) | 1288.9 mg | Standard Deviation 796.1 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | MMF dose, 6 months PT (n=193, 201) | 2450 mg | Standard Deviation 748.9 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | PO/NG Cyclosporine dose, 6 months PT (n=184, 182) | 331.1 mg | Standard Deviation 121.7 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | MMF dose,12 months PT (n=188, 194) | 2380.1 mg | Standard Deviation 779.2 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | Cumulative corticosteroids,6 months PT(n=203, 206) | 955.4 mg | Standard Deviation 442.8 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | IV Cyclosporine dose, 6 months PT (n=2, 1) | 38.1 mg | — |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | PO/NG Cyclosporine dose, 12 months PT (n=170, 170) | 305.7 mg | Standard Deviation 116.6 |
| Placebo | Mean Maintenance Doses of Mycophenolate Mofetil, Cyclosporine, and Cumulative Dose of Corticosteroids at 6 and 12 Months PT | IV Cyclosporine dose, 12 months PT (n=4, 2) | 46.7 mg | Standard Deviation 18 |
Secondary
Median Change From Baseline for LDL/HDL Ratio
Time frame: From Baseline (Day -2) to 3 months, and 6 months
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daclizumab | Median Change From Baseline for LDL/HDL Ratio | LDL/HDL ratio,change at 3 months (n=91,89) | -0.44 ratio |
| Daclizumab | Median Change From Baseline for LDL/HDL Ratio | LDL/HDL ratio,change at 6 months (n=91, 99) | -0.50 ratio |
| Placebo | Median Change From Baseline for LDL/HDL Ratio | LDL/HDL ratio,change at 3 months (n=91,89) | -0.12 ratio |
| Placebo | Median Change From Baseline for LDL/HDL Ratio | LDL/HDL ratio,change at 6 months (n=91, 99) | -0.14 ratio |
Secondary
Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides)
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL, Change at 3 months (n=92,89) | 0.25 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | HDL, change at 6 months (n=102,112) | 0.23 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Total cholesterol, change at 6 months (n=126,130) | 0.28 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Triglycerides,change at 3 months (n=104,108) | 0.26 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL, Change at 6 months (n=91,99) | 0.03 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Triglycerides,change at 6 months (n=109,117) | 0.20 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Total cholesterol, change at 3 months (n=119,119) | 0.65 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL/HDL ratio,change at 3 months (n=91,89) | -0.44 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | HDL, change at 3 months (n=97, 101) | 0.34 mg/dL |
| Daclizumab | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL/HDL ratio,change at 6 months (n=91, 99) | -0.50 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | HDL, change at 3 months (n=97, 101) | 0.31 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Total cholesterol, change at 3 months (n=119,119) | 0.91 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Total cholesterol, change at 6 months (n=126,130) | 0.61 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL, Change at 3 months (n=92,89) | 0.34 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL, Change at 6 months (n=91,99) | 0.21 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL/HDL ratio,change at 6 months (n=91, 99) | -0.14 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | HDL, change at 6 months (n=102,112) | 0.20 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Triglycerides,change at 3 months (n=104,108) | 0.46 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | Triglycerides,change at 6 months (n=109,117) | 0.44 mg/dL |
| Placebo | Median Change From Baseline for Lipid Profile (Total Cholesterol, Low Density Lipoproteins, High Density Lipoproteins, and Triglycerides) | LDL/HDL ratio,change at 3 months (n=91,89) | -0.12 mg/dL |
Secondary
Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT
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
Population: 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 | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Daclizumab | Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT | Within 6 months (n= 77, 104) | 61 days |
| Daclizumab | Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT | Within 12 months (n=97, 116) | 96 days |
| Placebo | Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT | Within 6 months (n= 77, 104) | 21 days |
| Placebo | Median Time to First Acute Rejection Episode Within the First 6 Months and 12 Months PT | Within 12 months (n=97, 116) | 26 days |
Secondary
Number of Acute Rejection Episodes Per Participant Within the First 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.
Time frame: Within 6 months and 12 months PT
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 0 episode | 139 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 1 episode | 63 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 2 episodes | 12 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 3 episodes | 2 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 4 episodes | 0 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 0 episode | 119 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 1 episode | 68 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 2 episodes | 23 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 3 episodes | 3 participants |
| Daclizumab | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 4 episodes | 3 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 2 episodes | 19 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 0 episode | 114 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 0 episode | 102 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 1 episode | 82 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 4 episodes | 2 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 2 episodes | 19 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 1 episode | 90 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 3 episodes | 2 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 12 months, 3 episodes | 5 participants |
| Placebo | Number of Acute Rejection Episodes Per Participant Within the First 6 Months and 12 Months PT | Within 6 months, 4 episodes | 1 participants |
Secondary
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
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
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | 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 | 17 participants |
| Daclizumab | 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 12 months | 23 participants |
| Placebo | 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 | 19 participants |
| Placebo | 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 12 months | 21 participants |
Secondary
Number of Participants Who Developed Acute Rejection Episode Within the 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
Time frame: Up to 12 months PT
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Daclizumab | Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT | 97 participants |
| Placebo | Number of Participants Who Developed Acute Rejection Episode Within the 12 Months PT | 116 participants |
p-value: 0.06395% CI: [-17.7, 0.5]Cochran-Mantel-Haenszel
Secondary
Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any AEs | 214 participants |
| Daclizumab | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any SAE's | 108 participants |
| Daclizumab | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any AEs leading to premature discontinuation | 14 participants |
| Placebo | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any AEs | 207 participants |
| Placebo | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any SAE's | 102 participants |
| Placebo | Number of Participants With Any Adverse Events and Any Serious Adverse Event, and Adverse Events Leading to Premature Withdrawal | Any AEs leading to premature discontinuation | 11 participants |
Secondary
Number of Participants With Malignancies and Opportunistic Infections
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participants With Malignancies and Opportunistic Infections | Participants with malignancies | 11 participants |
| Daclizumab | Number of Participants With Malignancies and Opportunistic Infections | Participants with opportunistic infections | 71 participants |
| Placebo | Number of Participants With Malignancies and Opportunistic Infections | Participants with malignancies | 11 participants |
| Placebo | Number of Participants With Malignancies and Opportunistic Infections | Participants with opportunistic infections | 80 participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Creatinine-high (n=211, 203) | 66 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Carbondioxide-low (n=206, 197) | 12 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | LDH-high (n=194, 191) | 53 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Chloride-high (n=211, 203) | 1 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Albumin-low (n=198,197) | 47 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Chloride-low (n=211, 203) | 42 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | ALP-high (n=201, 200) | 15 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Potassium-high (n=211, 204) | 7 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total protein-high (n=195,196) | 5 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Potassium-low (n=211, 204) | 4 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total bilirubin-high (n=201, 200) | 28 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Sodium-high (n=211, 203) | 2 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total protein-low(n=195,196) | 85 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Sodium-low (n=211, 203) | 8 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | GGT-high (n=180, 175) | 90 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Calcium-low (n=207, 201) | 39 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Cholesterol-high (n=174, 174) | 3 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Glucose fasting-high (n=210, 203) | 28 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | BUN-high (n= 210, 200) | 93 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Glucose fasting-low (n=210, 203) | 3 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Triglycerides-high (n=164, 164) | 35 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Phosphate-high (n=199, 194) | 54 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | SGOT-high (n=201, 200) | 22 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Phosphate-low (n=199,194) | 32 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Carbondioxide-high (n=206, 197) | 27 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Uric acid high (n=191, 188) | 23 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | SGPT-high (n=200, 200) | 48 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Uric acid high (n=191, 188) | 20 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | SGPT-high (n=200, 200) | 45 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | ALP-high (n=201, 200) | 7 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | SGOT-high (n=201, 200) | 25 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | GGT-high (n=180, 175) | 74 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | LDH-high (n=194, 191) | 54 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total bilirubin-high (n=201, 200) | 20 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | BUN-high (n= 210, 200) | 95 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Creatinine-high (n=211, 203) | 64 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Albumin-low (n=198,197) | 50 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total protein-high (n=195,196) | 0 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Total protein-low(n=195,196) | 79 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Cholesterol-high (n=174, 174) | 4 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Triglycerides-high (n=164, 164) | 30 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Carbondioxide-high (n=206, 197) | 21 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Carbondioxide-low (n=206, 197) | 5 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Chloride-high (n=211, 203) | 3 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Chloride-low (n=211, 203) | 36 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Potassium-high (n=211, 204) | 7 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Potassium-low (n=211, 204) | 2 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Sodium-high (n=211, 203) | 1 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Sodium-low (n=211, 203) | 11 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Calcium-low (n=207, 201) | 44 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Glucose fasting-high (n=210, 203) | 27 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Glucose fasting-low (n=210, 203) | 3 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Phosphate-high (n=199, 194) | 48 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Biochemistry Parameters | Phosphate-low (n=199,194) | 26 participants |
Secondary
Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters
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
Population: 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 | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hemoglobin-low (n=210, 204) | 107 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Basophils-high (n=199, 195) | 4 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hematocrit-low (n=210, 203) | 116 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Eosinophils-high (n=199, 195) | 0 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Platelets-high (n=210, 203) | 2 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Lymphocytes-high (n=199, 198) | 2 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hematocrit-high (n=210, 203) | 0 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Monocytes-high (n=199, 198) | 5 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Platelets-low (n=210, 203) | 30 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Monocytes-low (n=199, 198) | 14 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hemoglobin-high (n=210, 204) | 0 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Neutrophils-low (n= 199, 198) | 33 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | RBC-high (n=209, 203) | 1 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | WBC-high (n=207, 201) | 61 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Lymphocytes-low (n=199, 198) | 157 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | WBC-low (n=207, 201) | 43 participants |
| Daclizumab | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | RBC-low (n=209, 203) | 116 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | WBC-low (n=207, 201) | 29 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hematocrit-high (n=210, 203) | 0 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hematocrit-low (n=210, 203) | 117 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hemoglobin-high (n=210, 204) | 0 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Hemoglobin-low (n=210, 204) | 112 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Platelets-high (n=210, 203) | 1 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Platelets-low (n=210, 203) | 22 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | RBC-high (n=209, 203) | 2 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | RBC-low (n=209, 203) | 106 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Basophils-high (n=199, 195) | 4 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Eosinophils-high (n=199, 195) | 0 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Lymphocytes-low (n=199, 198) | 157 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Monocytes-high (n=199, 198) | 6 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Monocytes-low (n=199, 198) | 20 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Neutrophils-low (n= 199, 198) | 33 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | WBC-high (n=207, 201) | 57 participants |
| Placebo | Number of Participants With Marked Laboratory Abnormalities: Hematology Parameters | Lymphocytes-high (n=199, 198) | 2 participants |
Secondary
Number of Participants With Worst ISHLT Biopsy Grade Within First 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
Time frame: Within 6 months and 12 months PT
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade II | 55 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade 0 | 7 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade 0 | 9 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IA | 56 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IIIA | 48 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IB | 22 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IB | 26 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade II | 51 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IIIB | 8 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IIIA | 63 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IA | 64 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IV | 1 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IV | 1 participants |
| Daclizumab | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IIIB | 11 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IV | 1 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade 0 | 5 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IA | 51 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IB | 28 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade II | 38 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IIIA | 74 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IIIB | 15 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 6 months, Grade IV | 1 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade 0 | 4 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IA | 39 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IB | 21 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade II | 47 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IIIA | 85 participants |
| Placebo | Number of Participants With Worst ISHLT Biopsy Grade Within First 6 Months and 12 Months PT | Within 12 months, Grade IIIB | 15 participants |
Comparison: Comparison of Daclizumab and Placebo for 6 months were presentedp-value: 0.0005Cochran-Mantel-Haenszel
Comparison: Comparison of Daclizumab and Placebo for 12 months were presentedp-value: 0.0008Cochran-Mantel-Haenszel
Secondary
Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT
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
Population: The randomized population included all participants who were randomized into the study, whether they received the study drug or not.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Daclizumab | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 12 months | 21 participants |
| Daclizumab | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 3 years | NA participants |
| Daclizumab | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 6 months | 16 participants |
| Placebo | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 12 months | 12 participants |
| Placebo | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 3 years | NA participants |
| Placebo | Number of Participant Who Died Within 6 Months 12 Months and 3 Years PT | Within 6 months | 10 participants |