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Efficacy and Safety of Everolimus With Enteric-Coated Mycophenolate Sodium (EC-MPS) in a Cyclosporine Microemulsion-free Regimen Compared to Standard Therapy in de Novo Renal Transplant Patients

Sponsor
Novartis (Industry)
Overall Status
Completed
CT.gov ID
NCT00154310
Collaborator
(none)
300
Enrollment
3
Locations
2
Arms
39
Duration (Months)
100
Patients Per Site
2.6
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether a calcineurin inhibitor (CNI)-free regimen with enteric-coated mycophenolate sodium (EC-MPS) and everolimus is as safe and well-tolerated as the standard regimen containing enteric-coated mycophenolate sodium (EC-MPS) and cyclosporine microemulsion, but results in better renal function.

Condition or Disease Intervention/Treatment Phase
Phase 4

Study Design

Study Type:
Interventional
Actual Enrollment :
300 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multi-center, Open-label, Prospective, Randomized, Parallel Group Study Investigating a CNI-free Regimen With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Everolimus in Comparison to Standard Therapy With Enteric-Coated Mycophenolate Sodium (EC-MPS) and Cyclosporine Microemulsion in de Novo Renal Transplant Patients
Study Start Date :
Jun 1, 2005
Actual Primary Completion Date :
Sep 1, 2008
Actual Study Completion Date :
Sep 1, 2008

Arms and Interventions

Arm Intervention/Treatment
Experimental: Everolimus + Mycophenolate sodium

Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant.

Drug: Everolimus
Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL.
Other Names:
  • certican

    • Drug: Enteric-coated mycophenolate sodium
    Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.
    Other Names:
  • Myfortic

    • Drug: Corticosteroids
    Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Active Comparator: Cyclosporine + Mycophenolate sodium

    Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.

    Drug: Cyclosporine
    Tablets orally twice a day to maintain protocol specific target blood levels
    Other Names:
  • Sandimmun Optoral

    • Drug: Enteric-coated mycophenolate sodium
    Enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day.
    Other Names:
  • Myfortic

    • Drug: Corticosteroids
    Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.

    Outcome Measures

    Primary Outcome Measures

    1. Renal Function (Nankivell Formula) at Month 12 Post Transplantation. [at Month 12 post transplantation]

      Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m^2.

    Secondary Outcome Measures

    1. Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death [Up to Month 12]

      The number of participants with occurrence of biopsy proven acute rejection (BPAR), graft loss, or death up to Month 12 during the randomized treatment period. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III according to Banff 97 classification. A graft core biopsy was performed prior to 24 hours following initiation of graft rejection therapy. The allograft is presumed to be lost on the day the patient starts dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.

    2. Number of Participants With Occurrence of Treatment Failures [up to or at Month 12]

      Treatment failures defined as a composite endpoint of biopsy proven acute rejection, graft loss, death, loss to follow up and discontinuations due to lack of efficacy or toxicity, or conversion to another regimen (at least one condition must be present).

    3. Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12 [Month 4.5 and Month 12]

      An updated 1991 Framingham coronary prediction algorithm was used to estimate the total risk of developing coronary heart diseases (CHD) over the course of 10 years. Risk was calculated separately for male and females. To calculate risk, points were assigned for each of the following risk factors: age, levels of LDL cholesterol, HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus. The sum of the individual risk factor points gives a total point score, which ranges from -5 to 18 for men and -16 to 24 for women. Higher points indicate a higher risk for CHD.

    4. Number of Participants Who Experienced an Adverse Event or Serious Adverse Event [Aes from end of core study period (month 12) to end of follow-up period (month 60)]

      Additional information about the number of participants who experienced Adverse Events (greater than 5%) or Serious Adverse Events can be found in the Adverse Event section.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 65 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria :

    The following inclusion criteria had to be present at BL 1 (Screening visit prior to transplantation):

    1. Males or females, aged 18 - 65 years

    2. Recipients of de novo cadaveric, living unrelated or living related kidney transplants

    3. Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at BL 1, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility

    4. Patients who are willing and able to participate in the study and from whom written informed consent has been obtained

    Of all patients included into the study at BL 1 (prior to transplantation), those who continued into the randomized study period had to meet the following condition at BL 2, prior to randomization:

    1. Patients had to be on an immunosuppressive regimen with EC-MPS (target dose; 1440 mg/day, if tolerated; minimal dose: 720 mg/day), cyclosporine and corticosteroids

    2. Patients with an actual serum creatinine =< 3.0 mg/dl

    Exclusion Criteria:

    The following exclusion criteria must not be present at BL 1 (Screening visit prior to transplantation):

    1. More than one previous renal transplantation

    2. Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney

    3. Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)

    4. Patients who are recipients of A-B-O incompatible transplants

    5. Patients with a historical or current peak PRA of > 25%

    6. Patients with already existing antibodies against the HLA-type of the receiving transplant

    7. Females of childbearing potential who are planning to become pregnant, who are pregnant and/or lactating, who are unwilling to use effective means of contraception

    Of all patients included into the study at BL 1 (prior to transplantation), those who met one or more of the following criteria at BL 2, prior to randomization, should not continue into the randomized study period:

    1. Graft loss or death

    2. Changes to the immunosuppressive regimen prior to randomization due to immunologic reasons

    3. Patients who suffered from severe rejection (>= BANFF II acute rejection), recurrent acute rejection, or steroid resistant acute rejection

    4. Proteinuria > 1g/day

    Other protocol-defined exclusion criteria may apply.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Novartis Investigational Sites Nurnberg Germany
    2 Novartis Pharma AG Basel Switzerland
    3 Novartis Investigational Sites Bern Switzerland

    Sponsors and Collaborators

    • Novartis

    Investigators

    • Study Director: Novartis, Novartis

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00154310
    Other Study ID Numbers:
    • CRAD001A2418
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Nov 13, 2013
    Last Verified:
    Oct 1, 2013
    Keywords provided by Novartis
    Renal transplantation, everolimus, immunosuppressants, CNI-free
    Additional relevant MeSH terms:
    Cyclosporine
    Mycophenolic Acid
    Everolimus
    Cyclosporins

    Study Results

    Participant Flow

    Recruitment Details This study was an open-label, randomized, parallel-group, multi-center study with two treatment groups, cyclosporine continuation and cyclosporine withdrawal starting from Month 4.5 post-transplant. Study started in June 2005 and ended in September 2008.
    Pre-assignment Detail
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Period Title: Overall Study
    STARTED 155 145
    COMPLETED 118 117
    NOT COMPLETED 37 28

    Baseline Characteristics

    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium Total
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year. Total of all reporting groups
    Overall Participants 155 145 300
    Age (Years) [Mean (Standard Deviation) ]
    Mean (Standard Deviation) [Years]
    46.9
    (11.67)
    46.7
    (11.85)
    46.8
    (11.73)
    Sex: Female, Male (Count of Participants)
    Female
    53
    34.2%
    59
    40.7%
    112
    37.3%
    Male
    102
    65.8%
    86
    59.3%
    188
    62.7%

    Outcome Measures

    1. Primary Outcome
    Title Renal Function (Nankivell Formula) at Month 12 Post Transplantation.
    Description Renal function at the end of the trial assessed as mean absolute values of the glomerular filtration rate (GFR) calculated by Nankivell formula 12 months after renal transplantation. The Nankivell formula: GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)^2 + C ; where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kg, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. Estimated GFR is expressed in mL/min per 1.73m^2.
    Time Frame at Month 12 post transplantation

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat Population (randomized patients); Last Observation Carried Forward (LOCF). One patient in
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Measure Participants 154 145
    Mean (Standard Deviation) [mL/min /1.73m^2]
    71.84
    (18.53)
    61.24
    (16.65)
    2. Secondary Outcome
    Title Number of Participants With Occurrence of Biopsy Proven Acute Rejection (BPAR), Graft Loss or Death
    Description The number of participants with occurrence of biopsy proven acute rejection (BPAR), graft loss, or death up to Month 12 during the randomized treatment period. BPAR was defined as a biopsy graded IA, IB, IIA, IIB or III according to Banff 97 classification. A graft core biopsy was performed prior to 24 hours following initiation of graft rejection therapy. The allograft is presumed to be lost on the day the patient starts dialysis and was not able to subsequently be removed from dialysis. If the patient underwent a graft nephrectomy, then the day of nephrectomy was the day of graft loss.
    Time Frame Up to Month 12

    Outcome Measure Data

    Analysis Population Description
    Intent to Treat Population (Randomized Patients)
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Measure Participants 154 146
    BPAR: Yes
    15
    9.7%
    5
    3.4%
    BPAR: No
    139
    89.7%
    141
    97.2%
    Graft Loss: Yes
    0
    0%
    0
    0%
    Graft Loss: No
    154
    99.4%
    146
    100.7%
    Death: Yes
    0
    0%
    1
    0.7%
    Death: No
    154
    99.4%
    145
    100%
    3. Secondary Outcome
    Title Number of Participants With Occurrence of Treatment Failures
    Description Treatment failures defined as a composite endpoint of biopsy proven acute rejection, graft loss, death, loss to follow up and discontinuations due to lack of efficacy or toxicity, or conversion to another regimen (at least one condition must be present).
    Time Frame up to or at Month 12

    Outcome Measure Data

    Analysis Population Description
    Intention to treat (ITT) population (Randomized Patients).
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Measure Participants 154 146
    Treatment failure: Yes
    29
    18.7%
    23
    15.9%
    Treatment failure: No
    125
    80.6%
    123
    84.8%
    4. Secondary Outcome
    Title Changes in Cardiovascular Risk From Month 4.5 to Final Assessment at Month 12
    Description An updated 1991 Framingham coronary prediction algorithm was used to estimate the total risk of developing coronary heart diseases (CHD) over the course of 10 years. Risk was calculated separately for male and females. To calculate risk, points were assigned for each of the following risk factors: age, levels of LDL cholesterol, HDL cholesterol, blood pressure, cigarette smoking, and diabetes mellitus. The sum of the individual risk factor points gives a total point score, which ranges from -5 to 18 for men and -16 to 24 for women. Higher points indicate a higher risk for CHD.
    Time Frame Month 4.5 and Month 12

    Outcome Measure Data

    Analysis Population Description
    Safety Population for whom data was available at Month 4.5 and end of treatment.
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Measure Participants 155 145
    Male (n= 55, 37)
    0.5
    (1.87)
    0.1
    (1.86)
    Female (n= 22, 35)
    0.0
    (2.01)
    0.8
    (2.70)
    Total Population (n= 77, 72)
    0.4
    (1.91)
    0.4
    (2.32)
    5. Secondary Outcome
    Title Number of Participants Who Experienced an Adverse Event or Serious Adverse Event
    Description Additional information about the number of participants who experienced Adverse Events (greater than 5%) or Serious Adverse Events can be found in the Adverse Event section.
    Time Frame Aes from end of core study period (month 12) to end of follow-up period (month 60)

    Outcome Measure Data

    Analysis Population Description
    Safety Population consisted of all participants in whom transplantation was performed and who were treated with at least one dose of any immunosuppressive medication.
    Arm/Group Title Everolimus + Mycophenolate Sodium Cyclosporine + Mycophenolate Sodium
    Arm/Group Description Everolimus tablets orally twice a day to maintain a level of 6- 10 ng/mL and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5 mg prednisolone or equivalent and had to be continued throughout the first year. Cyclosporine withdrawal started from Month 4.5 post-transplant. Cyclosporine tablets orally twice a day to achieve protocol specific target levels and enteric-coated mycophenolate sodium orally twice a day to achieve a target dose of 1440 mg/day. Corticosteroids were added to the immunosuppressive regimen with a minimum dose of 5mg prednisolone or equivalent and had to be continued throughout the first year.
    Measure Participants 155 145
    Adverse Events
    155
    100%
    145
    100%
    Serious Adverse Events
    95
    61.3%
    86
    59.3%

    Adverse Events

    Time Frame
    Adverse Event Reporting Description
    Arm/Group Title Certican Sandimmun Optoral
    Arm/Group Description Certican Sandimmun Optoral
    All Cause Mortality
    Certican Sandimmun Optoral
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total / (NaN) / (NaN)
    Serious Adverse Events
    Certican Sandimmun Optoral
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 103/155 (66.5%) 93/145 (64.1%)
    Blood and lymphatic system disorders
    Hypochromic anaemia 1/155 (0.6%) 0/145 (0%)
    Leukocytosis 0/155 (0%) 1/145 (0.7%)
    Leukopenia 0/155 (0%) 1/145 (0.7%)
    Thrombocytopenia 1/155 (0.6%) 0/145 (0%)
    Cardiac disorders
    Acute coronary syndrome 1/155 (0.6%) 0/145 (0%)
    Arrhythmia 0/155 (0%) 1/145 (0.7%)
    Atrial fibrillation 2/155 (1.3%) 0/145 (0%)
    Cardiac arrest 1/155 (0.6%) 0/145 (0%)
    Cardiac failure chronic 1/155 (0.6%) 0/145 (0%)
    Coronary artery disease 1/155 (0.6%) 2/145 (1.4%)
    Myocardial infarction 3/155 (1.9%) 1/145 (0.7%)
    Myopericarditis 1/155 (0.6%) 0/145 (0%)
    Supraventricular tachycardia 1/155 (0.6%) 0/145 (0%)
    Ventricular tachycardia 1/155 (0.6%) 1/145 (0.7%)
    Congenital, familial and genetic disorders
    Congenital cystic kidney disease 1/155 (0.6%) 1/145 (0.7%)
    Pyloric stenosis 0/155 (0%) 1/145 (0.7%)
    Ear and labyrinth disorders
    Deafness 1/155 (0.6%) 0/145 (0%)
    Tinnitus 1/155 (0.6%) 0/145 (0%)
    Endocrine disorders
    Hyperparathyroidism 0/155 (0%) 1/145 (0.7%)
    Hyperparathyroidism secondary 1/155 (0.6%) 1/145 (0.7%)
    Eye disorders
    Amaurosis fugax 0/155 (0%) 1/145 (0.7%)
    Gastrointestinal disorders
    Abdominal pain 0/155 (0%) 1/145 (0.7%)
    Colitis 2/155 (1.3%) 0/145 (0%)
    Constipation 1/155 (0.6%) 0/145 (0%)
    Diarrhoea 6/155 (3.9%) 4/145 (2.8%)
    Enteritis 2/155 (1.3%) 1/145 (0.7%)
    Gastric polyps 0/155 (0%) 1/145 (0.7%)
    Gastritis erosive 1/155 (0.6%) 0/145 (0%)
    Inguinal hernia 0/155 (0%) 1/145 (0.7%)
    Nausea 0/155 (0%) 1/145 (0.7%)
    Periodontitis 1/155 (0.6%) 0/145 (0%)
    Peritoneal fibrosis 0/155 (0%) 1/145 (0.7%)
    Peritoneal haemorrhage 1/155 (0.6%) 0/145 (0%)
    Peritonitis 0/155 (0%) 1/145 (0.7%)
    Retroperitoneal haematoma 0/155 (0%) 1/145 (0.7%)
    Small intestinal perforation 1/155 (0.6%) 0/145 (0%)
    Subileus 0/155 (0%) 1/145 (0.7%)
    Vomiting 1/155 (0.6%) 1/145 (0.7%)
    General disorders
    Catheter site haematoma 0/155 (0%) 1/145 (0.7%)
    Fat necrosis 0/155 (0%) 1/145 (0.7%)
    Generalised oedema 1/155 (0.6%) 0/145 (0%)
    Hernia 0/155 (0%) 2/145 (1.4%)
    Hernia obstructive 1/155 (0.6%) 0/145 (0%)
    Impaired healing 0/155 (0%) 1/145 (0.7%)
    Non-cardiac chest pain 0/155 (0%) 1/145 (0.7%)
    Oedema peripheral 0/155 (0%) 2/145 (1.4%)
    Pyrexia 5/155 (3.2%) 1/145 (0.7%)
    Hepatobiliary disorders
    Hydrocholecystis 0/155 (0%) 1/145 (0.7%)
    Immune system disorders
    Transplant rejection 0/155 (0%) 1/145 (0.7%)
    Infections and infestations
    Aspergilloma 1/155 (0.6%) 0/145 (0%)
    Bacterial infection 0/155 (0%) 1/145 (0.7%)
    Bronchitis 2/155 (1.3%) 0/145 (0%)
    Bronchopulmonary aspergillosis 1/155 (0.6%) 0/145 (0%)
    Chronic sinusitis 0/155 (0%) 1/145 (0.7%)
    Cystitis 1/155 (0.6%) 0/145 (0%)
    Cytomegalovirus infection 6/155 (3.9%) 5/145 (3.4%)
    Diverticulitis 1/155 (0.6%) 0/145 (0%)
    Endocarditis 1/155 (0.6%) 0/145 (0%)
    Enterococcal infection 0/155 (0%) 1/145 (0.7%)
    Erysipelas 0/155 (0%) 2/145 (1.4%)
    Febrile infection 1/155 (0.6%) 0/145 (0%)
    Gastroenteritis 7/155 (4.5%) 4/145 (2.8%)
    Gastroenteritis salmonella 1/155 (0.6%) 0/145 (0%)
    Gastroenteritis viral 1/155 (0.6%) 0/145 (0%)
    Gastrointestinal infection 2/155 (1.3%) 1/145 (0.7%)
    Herpes zoster 0/155 (0%) 3/145 (2.1%)
    Human polyomavirus infection 0/155 (0%) 1/145 (0.7%)
    Infected lymphocele 0/155 (0%) 1/145 (0.7%)
    Infection 2/155 (1.3%) 1/145 (0.7%)
    Lung infection 1/155 (0.6%) 0/145 (0%)
    Nasopharyngitis 1/155 (0.6%) 0/145 (0%)
    Pneumocystis jiroveci pneumonia 3/155 (1.9%) 2/145 (1.4%)
    Pneumonia 8/155 (5.2%) 16/145 (11%)
    Pyelonephritis 4/155 (2.6%) 3/145 (2.1%)
    Renal cyst infection 1/155 (0.6%) 1/145 (0.7%)
    Respiratory tract infection 1/155 (0.6%) 0/145 (0%)
    Sepsis 1/155 (0.6%) 1/145 (0.7%)
    Shunt infection 0/155 (0%) 2/145 (1.4%)
    Sinusitis 2/155 (1.3%) 0/145 (0%)
    Superinfection 1/155 (0.6%) 0/145 (0%)
    Tracheitis 0/155 (0%) 1/145 (0.7%)
    Urinary tract infection 18/155 (11.6%) 14/145 (9.7%)
    Urosepsis 5/155 (3.2%) 4/145 (2.8%)
    Viral upper respiratory tract infection 1/155 (0.6%) 0/145 (0%)
    Wound infection 0/155 (0%) 1/145 (0.7%)
    Injury, poisoning and procedural complications
    Abdominal wound dehiscence 1/155 (0.6%) 0/145 (0%)
    Anastomotic complication 2/155 (1.3%) 0/145 (0%)
    Anastomotic haemorrhage 1/155 (0.6%) 0/145 (0%)
    Arteriovenous fistula thrombosis 0/155 (0%) 1/145 (0.7%)
    Chronic allograft nephropathy 1/155 (0.6%) 0/145 (0%)
    Complications of transplanted kidney 3/155 (1.9%) 7/145 (4.8%)
    Fat embolism 0/155 (0%) 1/145 (0.7%)
    Femur fracture 0/155 (0%) 1/145 (0.7%)
    Foot fracture 0/155 (0%) 1/145 (0.7%)
    Incision site haematoma 1/155 (0.6%) 0/145 (0%)
    Muscle rupture 1/155 (0.6%) 0/145 (0%)
    Operative haemorrhage 1/155 (0.6%) 0/145 (0%)
    Perirenal haematoma 0/155 (0%) 1/145 (0.7%)
    Post procedural haematoma 0/155 (0%) 1/145 (0.7%)
    Post procedural haemorrhage 1/155 (0.6%) 0/145 (0%)
    Postoperative hernia 0/155 (0%) 1/145 (0.7%)
    Renal haematoma 1/155 (0.6%) 0/145 (0%)
    Renal lymphocele 2/155 (1.3%) 0/145 (0%)
    Seroma 3/155 (1.9%) 0/145 (0%)
    Shunt thrombosis 0/155 (0%) 2/145 (1.4%)
    Spinal compression fracture 1/155 (0.6%) 0/145 (0%)
    Subcutaneous haematoma 0/155 (0%) 1/145 (0.7%)
    Transplant failure 1/155 (0.6%) 1/145 (0.7%)
    Urethral injury 1/155 (0.6%) 0/145 (0%)
    Wound dehiscence 1/155 (0.6%) 4/145 (2.8%)
    Investigations
    Blood creatinine increased 10/155 (6.5%) 15/145 (10.3%)
    Blood urea increased 1/155 (0.6%) 0/145 (0%)
    Cytomegalovirus test 1/155 (0.6%) 0/145 (0%)
    Haemoglobin decreased 0/155 (0%) 1/145 (0.7%)
    Occult blood positive 1/155 (0.6%) 0/145 (0%)
    Transaminases increased 0/155 (0%) 1/145 (0.7%)
    Metabolism and nutrition disorders
    Dehydration 1/155 (0.6%) 3/145 (2.1%)
    Diabetes mellitus 1/155 (0.6%) 0/145 (0%)
    Fluid retention 1/155 (0.6%) 0/145 (0%)
    Hypercalcaemia 0/155 (0%) 1/145 (0.7%)
    Hyperglycaemia 0/155 (0%) 1/145 (0.7%)
    Hyperkalaemia 1/155 (0.6%) 0/145 (0%)
    Hyponatraemia 0/155 (0%) 1/145 (0.7%)
    Tetany 1/155 (0.6%) 0/145 (0%)
    Musculoskeletal and connective tissue disorders
    Arthritis 0/155 (0%) 1/145 (0.7%)
    Arthropathy 0/155 (0%) 1/145 (0.7%)
    Haemarthrosis 1/155 (0.6%) 0/145 (0%)
    Myopathy steroid 1/155 (0.6%) 0/145 (0%)
    Osteonecrosis 1/155 (0.6%) 1/145 (0.7%)
    Pain in extremity 0/155 (0%) 1/145 (0.7%)
    Rhabdomyolysis 0/155 (0%) 1/145 (0.7%)
    Synovial cyst 1/155 (0.6%) 0/145 (0%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma 3/155 (1.9%) 2/145 (1.4%)
    Bladder cancer 1/155 (0.6%) 0/145 (0%)
    Bowen's disease 1/155 (0.6%) 0/145 (0%)
    Fibrous histiocytoma 0/155 (0%) 1/145 (0.7%)
    Kaposi's sarcoma 0/155 (0%) 1/145 (0.7%)
    Neoplasm skin 1/155 (0.6%) 0/145 (0%)
    Parathyroid tumour benign 0/155 (0%) 2/145 (1.4%)
    Prostate cancer 0/155 (0%) 1/145 (0.7%)
    Renal cell carcinoma 2/155 (1.3%) 0/145 (0%)
    Squamous cell carcinoma 2/155 (1.3%) 0/145 (0%)
    Thyroid neoplasm 0/155 (0%) 1/145 (0.7%)
    Uterine leiomyoma 1/155 (0.6%) 0/145 (0%)
    Nervous system disorders
    Aphasia 1/155 (0.6%) 0/145 (0%)
    Cerebrovascular accident 1/155 (0.6%) 0/145 (0%)
    Convulsion 1/155 (0.6%) 0/145 (0%)
    Psychiatric disorders
    Depression 1/155 (0.6%) 1/145 (0.7%)
    Dysphoria 1/155 (0.6%) 0/145 (0%)
    Psychiatric decompensation 1/155 (0.6%) 0/145 (0%)
    Renal and urinary disorders
    Focal segmental glomerulosclerosis 1/155 (0.6%) 0/145 (0%)
    Hydronephrosis 3/155 (1.9%) 0/145 (0%)
    IgA nephropathy 1/155 (0.6%) 0/145 (0%)
    Nephritis autoimmune 1/155 (0.6%) 0/145 (0%)
    Nephropathy 1/155 (0.6%) 0/145 (0%)
    Nephropathy toxic 1/155 (0.6%) 0/145 (0%)
    Nephrosclerosis 1/155 (0.6%) 0/145 (0%)
    Proteinuria 1/155 (0.6%) 0/145 (0%)
    Renal artery stenosis 3/155 (1.9%) 1/145 (0.7%)
    Renal disorder 0/155 (0%) 1/145 (0.7%)
    Renal failure 0/155 (0%) 1/145 (0.7%)
    Renal failure acute 1/155 (0.6%) 0/145 (0%)
    Renal haemorrhage 1/155 (0.6%) 0/145 (0%)
    Renal impairment 1/155 (0.6%) 0/145 (0%)
    Renal tubular disorder 1/155 (0.6%) 0/145 (0%)
    Ureteral necrosis 1/155 (0.6%) 1/145 (0.7%)
    Ureteric stenosis 3/155 (1.9%) 3/145 (2.1%)
    Urethral discharge 1/155 (0.6%) 0/145 (0%)
    Urethral perforation 1/155 (0.6%) 0/145 (0%)
    Urethral stenosis 1/155 (0.6%) 1/145 (0.7%)
    Urinary incontinence 0/155 (0%) 1/145 (0.7%)
    Urinary retention 2/155 (1.3%) 2/145 (1.4%)
    Urinary tract disorder 1/155 (0.6%) 0/145 (0%)
    Urinary tract obstruction 2/155 (1.3%) 0/145 (0%)
    Urinoma 2/155 (1.3%) 0/145 (0%)
    Vesicoureteric reflux 1/155 (0.6%) 1/145 (0.7%)
    Reproductive system and breast disorders
    Benign prostatic hyperplasia 0/155 (0%) 1/145 (0.7%)
    Cervical dysplasia 1/155 (0.6%) 0/145 (0%)
    Ovarian cyst 1/155 (0.6%) 0/145 (0%)
    Pelvic congestion 0/155 (0%) 1/145 (0.7%)
    Postmenopausal haemorrhage 1/155 (0.6%) 0/145 (0%)
    Scrotal oedema 0/155 (0%) 1/145 (0.7%)
    Vaginal haemorrhage 1/155 (0.6%) 0/145 (0%)
    Respiratory, thoracic and mediastinal disorders
    Acute respiratory distress syndrome 0/155 (0%) 1/145 (0.7%)
    Bronchitis chronic 0/155 (0%) 1/145 (0.7%)
    Dyspnoea 0/155 (0%) 2/145 (1.4%)
    Interstitial lung disease 0/155 (0%) 1/145 (0.7%)
    Lung infiltration 0/155 (0%) 1/145 (0.7%)
    Pulmonary embolism 3/155 (1.9%) 1/145 (0.7%)
    Respiratory arrest 1/155 (0.6%) 0/145 (0%)
    Respiratory failure 1/155 (0.6%) 1/145 (0.7%)
    Stridor 0/155 (0%) 1/145 (0.7%)
    Skin and subcutaneous tissue disorders
    Erythema nodosum 1/155 (0.6%) 0/145 (0%)
    Pyoderma gangrenosum 0/155 (0%) 1/145 (0.7%)
    Rash 1/155 (0.6%) 0/145 (0%)
    Skin ulcer 1/155 (0.6%) 0/145 (0%)
    Surgical and medical procedures
    Kidney anastomosis 0/155 (0%) 1/145 (0.7%)
    Vascular disorders
    Arterial restenosis 0/155 (0%) 1/145 (0.7%)
    Deep vein thrombosis 2/155 (1.3%) 0/145 (0%)
    Haematoma 3/155 (1.9%) 2/145 (1.4%)
    Haemorrhage 2/155 (1.3%) 0/145 (0%)
    Hypertension 2/155 (1.3%) 0/145 (0%)
    Hypertensive crisis 2/155 (1.3%) 0/145 (0%)
    Hypotension 0/155 (0%) 1/145 (0.7%)
    Lymphocele 9/155 (5.8%) 14/145 (9.7%)
    Peripheral artery aneurysm 1/155 (0.6%) 0/145 (0%)
    Shock haemorrhagic 2/155 (1.3%) 0/145 (0%)
    Thrombosis 0/155 (0%) 1/145 (0.7%)
    Venous thrombosis 1/155 (0.6%) 0/145 (0%)
    Venous thrombosis limb 1/155 (0.6%) 0/145 (0%)
    Other (Not Including Serious) Adverse Events
    Certican Sandimmun Optoral
    Affected / at Risk (%) # Events Affected / at Risk (%) # Events
    Total 155/155 (100%) 145/145 (100%)
    Blood and lymphatic system disorders
    Anaemia 43/155 (27.7%) 35/145 (24.1%)
    Leukocytosis 17/155 (11%) 22/145 (15.2%)
    Leukopenia 24/155 (15.5%) 24/145 (16.6%)
    Thrombocytopenia 18/155 (11.6%) 5/145 (3.4%)
    Ear and labyrinth disorders
    Vertigo 7/155 (4.5%) 9/145 (6.2%)
    Gastrointestinal disorders
    Abdominal pain 20/155 (12.9%) 14/145 (9.7%)
    Abdominal pain upper 12/155 (7.7%) 12/145 (8.3%)
    Aphthous stomatitis 22/155 (14.2%) 3/145 (2.1%)
    Constipation 82/155 (52.9%) 72/145 (49.7%)
    Diarrhoea 60/155 (38.7%) 42/145 (29%)
    Dyspepsia 15/155 (9.7%) 11/145 (7.6%)
    Flatulence 25/155 (16.1%) 20/145 (13.8%)
    Nausea 64/155 (41.3%) 59/145 (40.7%)
    Vomiting 38/155 (24.5%) 32/145 (22.1%)
    General disorders
    Asthenia 2/155 (1.3%) 9/145 (6.2%)
    Fatigue 7/155 (4.5%) 10/145 (6.9%)
    Impaired healing 8/155 (5.2%) 5/145 (3.4%)
    Oedema 44/155 (28.4%) 34/145 (23.4%)
    Oedema peripheral 38/155 (24.5%) 32/145 (22.1%)
    Pain 30/155 (19.4%) 26/145 (17.9%)
    Pyrexia 24/155 (15.5%) 22/145 (15.2%)
    Infections and infestations
    Bronchitis 16/155 (10.3%) 7/145 (4.8%)
    Cytomegalovirus infection 26/155 (16.8%) 24/145 (16.6%)
    Gastroenteritis 15/155 (9.7%) 17/145 (11.7%)
    Gastrointestinal infection 10/155 (6.5%) 7/145 (4.8%)
    Herpes zoster 8/155 (5.2%) 10/145 (6.9%)
    Human polyomavirus infection 8/155 (5.2%) 3/145 (2.1%)
    Infection 9/155 (5.8%) 9/145 (6.2%)
    Nasopharyngitis 49/155 (31.6%) 44/145 (30.3%)
    Oral herpes 11/155 (7.1%) 1/145 (0.7%)
    Pneumonia 16/155 (10.3%) 9/145 (6.2%)
    Respiratory tract infection 12/155 (7.7%) 12/145 (8.3%)
    Rhinitis 12/155 (7.7%) 8/145 (5.5%)
    Upper respiratory tract infection 12/155 (7.7%) 7/145 (4.8%)
    Urinary tract infection 90/155 (58.1%) 83/145 (57.2%)
    Wound infection 4/155 (2.6%) 11/145 (7.6%)
    Injury, poisoning and procedural complications
    Complications of transplanted kidney 21/155 (13.5%) 24/145 (16.6%)
    Procedural pain 50/155 (32.3%) 48/145 (33.1%)
    Wound complication 51/155 (32.9%) 46/145 (31.7%)
    Wound dehiscence 6/155 (3.9%) 8/145 (5.5%)
    Investigations
    Blood creatinine increased 51/155 (32.9%) 49/145 (33.8%)
    C-reactive protein increased 7/155 (4.5%) 8/145 (5.5%)
    Weight increased 8/155 (5.2%) 14/145 (9.7%)
    Metabolism and nutrition disorders
    Diabetes mellitus 19/155 (12.3%) 12/145 (8.3%)
    Fluid retention 6/155 (3.9%) 12/145 (8.3%)
    Hypercalcaemia 15/155 (9.7%) 25/145 (17.2%)
    Hypercholesterolaemia 45/155 (29%) 41/145 (28.3%)
    Hyperglycaemia 24/155 (15.5%) 16/145 (11%)
    Hyperkalaemia 18/155 (11.6%) 21/145 (14.5%)
    Hyperlipidaemia 23/155 (14.8%) 16/145 (11%)
    Hyperphosphataemia 11/155 (7.1%) 12/145 (8.3%)
    Hypertriglyceridaemia 11/155 (7.1%) 5/145 (3.4%)
    Hyperuricaemia 10/155 (6.5%) 20/145 (13.8%)
    Hypocalcaemia 23/155 (14.8%) 27/145 (18.6%)
    Hypokalaemia 45/155 (29%) 36/145 (24.8%)
    Hypomagnesaemia 8/155 (5.2%) 13/145 (9%)
    Hyponatraemia 6/155 (3.9%) 10/145 (6.9%)
    Hypophosphataemia 47/155 (30.3%) 43/145 (29.7%)
    Hypoproteinaemia 8/155 (5.2%) 11/145 (7.6%)
    Iron deficiency 3/155 (1.9%) 8/145 (5.5%)
    Metabolic acidosis 15/155 (9.7%) 10/145 (6.9%)
    Musculoskeletal and connective tissue disorders
    Arthralgia 16/155 (10.3%) 12/145 (8.3%)
    Back pain 26/155 (16.8%) 15/145 (10.3%)
    Muscle spasms 9/155 (5.8%) 10/145 (6.9%)
    Myalgia 10/155 (6.5%) 4/145 (2.8%)
    Pain in extremity 14/155 (9%) 5/145 (3.4%)
    Nervous system disorders
    Headache 25/155 (16.1%) 21/145 (14.5%)
    Tremor 10/155 (6.5%) 9/145 (6.2%)
    Psychiatric disorders
    Insomnia 35/155 (22.6%) 32/145 (22.1%)
    Sleep disorder 21/155 (13.5%) 20/145 (13.8%)
    Renal and urinary disorders
    Bladder pain 8/155 (5.2%) 11/145 (7.6%)
    Dysuria 7/155 (4.5%) 9/145 (6.2%)
    Haematuria 28/155 (18.1%) 31/145 (21.4%)
    Leukocyturia 22/155 (14.2%) 18/145 (12.4%)
    Polyuria 10/155 (6.5%) 16/145 (11%)
    Proteinuria 25/155 (16.1%) 25/145 (17.2%)
    Urinary retention 11/155 (7.1%) 4/145 (2.8%)
    Respiratory, thoracic and mediastinal disorders
    Cough 26/155 (16.8%) 29/145 (20%)
    Dyspnoea 19/155 (12.3%) 17/145 (11.7%)
    Skin and subcutaneous tissue disorders
    Acne 14/155 (9%) 11/145 (7.6%)
    Hypertrichosis 5/155 (3.2%) 8/145 (5.5%)
    Rash 8/155 (5.2%) 4/145 (2.8%)
    Vascular disorders
    Haematoma 8/155 (5.2%) 8/145 (5.5%)
    Hypertension 17/155 (11%) 22/145 (15.2%)
    Hypotension 22/155 (14.2%) 32/145 (22.1%)
    Lymphocele 17/155 (11%) 23/145 (15.9%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

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

    The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial.

    Results Point of Contact

    Name/Title Study Director
    Organization Novartis Pharmaceuticals
    Phone 862-778-8300
    Email
    Responsible Party:
    Novartis
    ClinicalTrials.gov Identifier:
    NCT00154310
    Other Study ID Numbers:
    • CRAD001A2418
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Nov 13, 2013
    Last Verified:
    Oct 1, 2013