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ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin Inhibitor Reduction in the Maintenance of Renal Transplant Recipients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00170846
Recruitment Status : Completed
First Posted : September 15, 2005
Results First Posted : May 2, 2011
Last Update Posted : January 27, 2015
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Renal Transplantation
Interventions Drug: Everolimus (RAD001)
Drug: Calcineurin Inhibitors (CNI)
Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
Drug: Steroids
Enrollment 394
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Hide Arm/Group Description Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose. Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Period Title: Overall Study
Started 123 127 144
Completed 112 108 131
Not Completed 11 19 13
Reason Not Completed
Subject withdrew Informed Consent             5             12             8
Lost to Follow-up             6             3             2
Death             0             3             3
Reason Missing             0             1             0
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction Total
Hide Arm/Group Description Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose. Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose. Total of all reporting groups
Overall Number of Baseline Participants 123 127 144 394
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 123 participants 127 participants 144 participants 394 participants
48.2  (12.18) 49.4  (11.81) 49.7  (12.95) 49.1  (12.34)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 123 participants 127 participants 144 participants 394 participants
Female
41
  33.3%
41
  32.3%
53
  36.8%
135
  34.3%
Male
82
  66.7%
86
  67.7%
91
  63.2%
259
  65.7%
Time since transplantation  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 123 participants 127 participants 144 participants 394 participants
5.8  (4.14) 5.4  (4.28) 5.4  (3.99) 5.6  (4.13)
1.Primary Outcome
Title Renal Function Assessed by Measured GFR (mGFR)
Hide Description The acceptable methods for GFR measurement were Chromium 51-Ethylenediaminetetra acetic acid (Cr-EDTA), Technetium 99-Diethylenetriaminepentacetic acid (Tc-DTPA), Iohexol clearance Inuline clearance and Iothalamate clearance. The method should have been consistent for a given patient at every time point.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
The modified ITT population included all ITT patients who had mGFR or calculated GFR (cGFR) at Month 24 based on all values including those collected after discontinuation of study medication.
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Hide Arm/Group Description:
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Overall Number of Participants Analyzed 103 94 109
Mean (Standard Deviation)
Unit of Measure: mL/min/1.73m^2
46.02  (20.358) 48.00  (22.033) 46.60  (21.079)
Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Group A: No RAD, Group B : CNI Withdrawal
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.6332
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 1.1241
Confidence Interval (2-Sided) 95%
-3.5077 to 5.7559
Estimation Comments [Not Specified]
Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Group A: No RAD, Group C: CNI Reduction
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7943
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
Method of Estimation Estimation Parameter Difference in LS means
Estimated Value 0.5933
Confidence Interval (2-Sided) 95%
-3.8815 to 5.0682
Estimation Comments [Not Specified]
2.Secondary Outcome
Title Number of Participants With Safety Parameters
Hide Description The selected safety parameters (such as hypertension, hyperlipidemia, diabetes mellitus, anemia, malignancies ) were derived based on adverse events preferred terms defined in the analysis plan.
Time Frame 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Safety Population. The Safety Population consisted of all randomized patients who received at least one dose of study drug and had at least one post-baseline safety assessment.
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Hide Arm/Group Description:
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Overall Number of Participants Analyzed 123 127 144
Measure Type: Number
Unit of Measure: Participants
Hypertension, Yes 6 13 9
Hypertension, No 117 114 135
Hyperlipidemia, Yes 6 18 11
Hyperlipidemia, No 117 109 133
Diabetes mellitus, Yes 4 6 7
Diabetes mellitus, No 119 121 137
Anemia, Yes 25 45 46
Anemia, No 98 82 98
Malignancies, Yes 7 9 11
Malignancies, No 116 118 133
3.Post-Hoc Outcome
Title Change in mGFR by Baseline Calculated Creatinine Clearance (Cockcroft-Gault Formula)
Hide Description

Cockcroft-Gault formula (CrCl):

Creatinine Clearance [mL/min] = CrCl (males) = (140 - A) * W / (72 * C) (males), CrCl (females) = CrCl (males) * 0.85,

Where:

  • A is age [years]
  • W is body weight [kg]
  • C is the serum concentration of creatinine [mg/dL]
Time Frame Baseline and 24 months
Hide Outcome Measure Data
Hide Analysis Population Description
Per Protocol Population. The per-protocol (PP) population consisted of the ITT patients excluding those patients with major protocol deviations and those patients who were not able to initiate their randomized regimens as scheduled.
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Hide Arm/Group Description:
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Overall Number of Participants Analyzed 112 110 124
Mean (Standard Deviation)
Unit of Measure: mL/min
Baseline CrCl(CG) ≤ 50 :(n= 32, 28, 32):- Change 1.55  (12.833) -5.75  (14.712) 0.82  (19.445)
Baseline CrCl(CG) > 50 : (n=31, 29, 39):-Change -2.55  (19.562) 7.32  (21.051) -0.24  (17.551)
Time Frame [Not Specified]
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Hide Arm/Group Description Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose. Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
All-Cause Mortality
Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/--   --/-- 
Hide Serious Adverse Events
Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   52/123 (42.28%)   72/127 (56.69%)   78/144 (54.17%) 
Blood and lymphatic system disorders       
Anaemia † 1  3/123 (2.44%)  5/127 (3.94%)  3/144 (2.08%) 
Haemolytic uraemic syndrome † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Iron deficiency anaemia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Leukopenia † 1  0/123 (0.00%)  2/127 (1.57%)  0/144 (0.00%) 
Lymphadenopathy † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Pancytopenia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Thrombocytopenia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cardiac disorders       
Acute coronary syndrome † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Acute myocardial infarction † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Angina pectoris † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Aortic valve incompetence † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Atrial fibrillation † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Bradycardia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Cardiac arrest † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cardiac failure † 1  0/123 (0.00%)  2/127 (1.57%)  0/144 (0.00%) 
Cardiac failure acute † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Cardiac failure congestive † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cardio-respiratory arrest † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Coronary artery stenosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Left ventricular failure † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Tachycardia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Ear and labyrinth disorders       
Vertigo † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Eye disorders       
Papilloedema † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Gastrointestinal disorders       
Abdominal hernia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Abdominal pain † 1  0/123 (0.00%)  1/127 (0.79%)  3/144 (2.08%) 
Abdominal pain upper † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Colitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Diarrhoea † 1  2/123 (1.63%)  6/127 (4.72%)  12/144 (8.33%) 
Dysphagia † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Gastritis † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Gastritis erosive † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Gastrointestinal haemorrhage † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Gastrooesophageal reflux disease † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Glossodynia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Nausea † 1  0/123 (0.00%)  1/127 (0.79%)  2/144 (1.39%) 
Pancreatitis acute † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Peritoneal haemorrhage † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Peritonitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Reflux oesophagitis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Vomiting † 1  1/123 (0.81%)  5/127 (3.94%)  4/144 (2.78%) 
General disorders       
Asthenia † 1  0/123 (0.00%)  0/127 (0.00%)  3/144 (2.08%) 
Chest discomfort † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Chest pain † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cyst † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Death † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Face oedema † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Localised oedema † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Non-cardiac chest pain † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Oedema peripheral † 1  1/123 (0.81%)  1/127 (0.79%)  3/144 (2.08%) 
Pyrexia † 1  1/123 (0.81%)  4/127 (3.15%)  11/144 (7.64%) 
Sudden death † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Hepatobiliary disorders       
Cholecystitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Cholecystitis acute † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cholelithiasis † 1  0/123 (0.00%)  1/127 (0.79%)  2/144 (1.39%) 
Immune system disorders       
Kidney transplant rejection † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Transplant rejection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Infections and infestations       
Abdominal infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Abscess fungal † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Abscess neck † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Anal abscess † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Breast abscess † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Bronchiectasis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Bronchitis † 1  0/123 (0.00%)  0/127 (0.00%)  3/144 (2.08%) 
Bronchitis viral † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Bronchopneumonia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Carbuncle † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Cardiac infection † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Catheter sepsis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Cellulitis † 1  2/123 (1.63%)  3/127 (2.36%)  4/144 (2.78%) 
Cryptosporidiosis infection † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Cytomegalovirus infection † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Disseminated tuberculosis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Diverticulitis † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Endocarditis † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Enterocolitis infectious † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Escherichia infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Furuncle † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Gangrene † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Gastroenteritis † 1  5/123 (4.07%)  4/127 (3.15%)  6/144 (4.17%) 
Hepatitis B † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Hepatitis E † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Herpes zoster † 1  0/123 (0.00%)  2/127 (1.57%)  1/144 (0.69%) 
Infected sebaceous cyst † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Influenza † 1  0/123 (0.00%)  2/127 (1.57%)  0/144 (0.00%) 
Lobar pneumonia † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Localised infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Lower respiratory tract infection † 1  1/123 (0.81%)  1/127 (0.79%)  2/144 (1.39%) 
Lower respiratory tract infection viral † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Lung infection † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Lung infection pseudomonal † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Meningitis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Mucormycosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Nail infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Nasopharyngitis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Oophoritis † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Oral infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Otitis media † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Perineal abscess † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Pneumonia † 1  5/123 (4.07%)  2/127 (1.57%)  6/144 (4.17%) 
Pneumonia bacterial † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Postoperative wound infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Pulmonary tuberculosis † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Pyelonephritis † 1  0/123 (0.00%)  1/127 (0.79%)  5/144 (3.47%) 
Pyelonephritis acute † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Respiratory tract infection † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Salmonella sepsis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Sepsis † 1  1/123 (0.81%)  3/127 (2.36%)  2/144 (1.39%) 
Sialoadenitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Sinusitis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Skin infection † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Tooth abscess † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Tuberculosis bladder † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Tuberculosis of genitourinary system † 1  1/123 (0.81%)  1/127 (0.79%)  0/144 (0.00%) 
Upper respiratory tract infection † 1  0/123 (0.00%)  4/127 (3.15%)  1/144 (0.69%) 
Urethral abscess † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Urinary tract infection † 1  6/123 (4.88%)  5/127 (3.94%)  10/144 (6.94%) 
Urosepsis † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Varicella † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Viral infection † 1  1/123 (0.81%)  2/127 (1.57%)  1/144 (0.69%) 
Wound infection † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Injury, poisoning and procedural complications       
Arteriovenous fistula site complication † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Arteriovenous fistula thrombosis † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Chronic allograft nephropathy † 1  1/123 (0.81%)  3/127 (2.36%)  0/144 (0.00%) 
Complications of transplanted kidney † 1  1/123 (0.81%)  2/127 (1.57%)  1/144 (0.69%) 
Concussion † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Femur fracture † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Hand fracture † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Limb injury † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Muscle injury † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Post procedural complication † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Post procedural haematuria † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Postoperative wound complication † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Procedural vomiting † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Renal graft loss † 1  4/123 (3.25%)  3/127 (2.36%)  9/144 (6.25%) 
Rib fracture † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Subdural haematoma † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Investigations       
Blood creatine phosphokinase MB increased † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Blood creatine phosphokinase increased † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Blood creatinine increased † 1  7/123 (5.69%)  7/127 (5.51%)  4/144 (2.78%) 
Blood folate decreased † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Blood urea increased † 1  1/123 (0.81%)  1/127 (0.79%)  0/144 (0.00%) 
Blood uric acid increased † 1  2/123 (1.63%)  0/127 (0.00%)  0/144 (0.00%) 
Protein urine † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Tuberculin test positive † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Urine output decreased † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Vitamin B12 decreased † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Weight decreased † 1  0/123 (0.00%)  2/127 (1.57%)  1/144 (0.69%) 
White blood cell count decreased † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Metabolism and nutrition disorders       
Acidosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Decreased appetite † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Dehydration † 1  0/123 (0.00%)  0/127 (0.00%)  3/144 (2.08%) 
Diabetes mellitus † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Diabetes mellitus inadequate control † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Fluid overload † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Gout † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Hypercalcaemia † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Hyperglycaemia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Hypocalcaemia † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Hypoglycaemia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Hypokalaemia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Hyponatraemia † 1  0/123 (0.00%)  2/127 (1.57%)  0/144 (0.00%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Back pain † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Bursitis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Musculoskeletal chest pain † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Myositis ossificans † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Osteitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Osteonecrosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)       
Basal cell carcinoma † 1  1/123 (0.81%)  2/127 (1.57%)  4/144 (2.78%) 
Basosquamous carcinoma of skin † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Benign uterine neoplasm † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Bowen's disease † 1  1/123 (0.81%)  0/127 (0.00%)  2/144 (1.39%) 
Breast cancer † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Lip neoplasm malignant stage unspecified † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Lung neoplasm malignant † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Malignant melanoma † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Metastatic malignant melanoma † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Prostate cancer † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Renal cell carcinoma † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Seborrhoeic keratosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Squamous cell carcinoma † 1  0/123 (0.00%)  3/127 (2.36%)  0/144 (0.00%) 
Squamous cell carcinoma of skin † 1  1/123 (0.81%)  1/127 (0.79%)  2/144 (1.39%) 
Thyroid cancer † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Transitional cell carcinoma † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Uterine leiomyoma † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Nervous system disorders       
Benign intracranial hypertension † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Brain stem infarction † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Cerebral infarction † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Convulsion † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Dizziness † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Headache † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Hemiplegia † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Ischaemic stroke † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Lethargy † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Loss of consciousness † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Nerve compression † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Partial seizures † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Syncope † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Tremor † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Vocal cord paralysis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Psychiatric disorders       
Depression † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Renal and urinary disorders       
Azotaemia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Glomerulonephritis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Haematuria † 1  2/123 (1.63%)  1/127 (0.79%)  2/144 (1.39%) 
Hydronephrosis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Nephrectasia † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Nephrotic syndrome † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Proteinuria † 1  1/123 (0.81%)  3/127 (2.36%)  0/144 (0.00%) 
Renal failure † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Renal failure acute † 1  2/123 (1.63%)  1/127 (0.79%)  1/144 (0.69%) 
Renal impairment † 1  0/123 (0.00%)  3/127 (2.36%)  2/144 (1.39%) 
Tubulointerstitial nephritis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Urethral obstruction † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Urinary bladder haemorrhage † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Vesicoureteric reflux † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Reproductive system and breast disorders       
Amenorrhoea † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Endometriosis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Epididymitis † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Ovarian cyst † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Respiratory, thoracic and mediastinal disorders       
Acute respiratory distress syndrome † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Bronchial disorder † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Chronic obstructive pulmonary disease † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Cough † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Dysphonia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Dyspnoea † 1  0/123 (0.00%)  2/127 (1.57%)  3/144 (2.08%) 
Interstitial lung disease † 1  0/123 (0.00%)  2/127 (1.57%)  2/144 (1.39%) 
Lung disorder † 1  1/123 (0.81%)  0/127 (0.00%)  1/144 (0.69%) 
Organising pneumonia † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Pneumonitis † 1  0/123 (0.00%)  1/127 (0.79%)  1/144 (0.69%) 
Pulmonary congestion † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Pulmonary embolism † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Pulmonary oedema † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Tachypnoea † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Skin and subcutaneous tissue disorders       
Dermatitis contact † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Eczema † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Erythema † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Skin oedema † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Vascular disorders       
Aortic aneurysm † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Arterial stenosis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Deep vein thrombosis † 1  0/123 (0.00%)  0/127 (0.00%)  2/144 (1.39%) 
Extremity necrosis † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Haematoma † 1  0/123 (0.00%)  1/127 (0.79%)  0/144 (0.00%) 
Hypertension † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Hypertensive crisis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Hypotension † 1  0/123 (0.00%)  0/127 (0.00%)  1/144 (0.69%) 
Iliac artery stenosis † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
Peripheral vascular disorder † 1  2/123 (1.63%)  1/127 (0.79%)  0/144 (0.00%) 
Varicose vein † 1  1/123 (0.81%)  0/127 (0.00%)  0/144 (0.00%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Group A: No RAD Group B : CNI Withdrawal Group C: CNI Reduction
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   97/123 (78.86%)   116/127 (91.34%)   126/144 (87.50%) 
Blood and lymphatic system disorders       
Anaemia † 1  22/123 (17.89%)  42/127 (33.07%)  40/144 (27.78%) 
Leukopenia † 1  5/123 (4.07%)  10/127 (7.87%)  3/144 (2.08%) 
Thrombocytopenia † 1  1/123 (0.81%)  10/127 (7.87%)  4/144 (2.78%) 
Gastrointestinal disorders       
Aphthous stomatitis † 1  2/123 (1.63%)  22/127 (17.32%)  9/144 (6.25%) 
Diarrhoea † 1  20/123 (16.26%)  36/127 (28.35%)  30/144 (20.83%) 
Mouth ulceration † 1  1/123 (0.81%)  15/127 (11.81%)  8/144 (5.56%) 
Nausea † 1  7/123 (5.69%)  9/127 (7.09%)  7/144 (4.86%) 
Vomiting † 1  7/123 (5.69%)  7/127 (5.51%)  9/144 (6.25%) 
General disorders       
Oedema † 1  0/123 (0.00%)  8/127 (6.30%)  6/144 (4.17%) 
Oedema peripheral † 1  12/123 (9.76%)  33/127 (25.98%)  37/144 (25.69%) 
Pyrexia † 1  6/123 (4.88%)  15/127 (11.81%)  16/144 (11.11%) 
Infections and infestations       
Bronchitis † 1  7/123 (5.69%)  6/127 (4.72%)  6/144 (4.17%) 
Nasopharyngitis † 1  8/123 (6.50%)  9/127 (7.09%)  13/144 (9.03%) 
Upper respiratory tract infection † 1  16/123 (13.01%)  11/127 (8.66%)  15/144 (10.42%) 
Urinary tract infection † 1  10/123 (8.13%)  20/127 (15.75%)  18/144 (12.50%) 
Investigations       
Blood creatine phosphokinase increased † 1  2/123 (1.63%)  7/127 (5.51%)  3/144 (2.08%) 
Blood creatinine increased † 1  15/123 (12.20%)  11/127 (8.66%)  10/144 (6.94%) 
Metabolism and nutrition disorders       
Decreased appetite † 1  2/123 (1.63%)  7/127 (5.51%)  3/144 (2.08%) 
Gout † 1  7/123 (5.69%)  4/127 (3.15%)  6/144 (4.17%) 
Hypercholesterolaemia † 1  5/123 (4.07%)  18/127 (14.17%)  24/144 (16.67%) 
Hyperlipidaemia † 1  6/123 (4.88%)  18/127 (14.17%)  11/144 (7.64%) 
Hypertriglyceridaemia † 1  2/123 (1.63%)  6/127 (4.72%)  11/144 (7.64%) 
Hypokalaemia † 1  3/123 (2.44%)  12/127 (9.45%)  1/144 (0.69%) 
Musculoskeletal and connective tissue disorders       
Arthralgia † 1  7/123 (5.69%)  5/127 (3.94%)  9/144 (6.25%) 
Back pain † 1  7/123 (5.69%)  1/127 (0.79%)  2/144 (1.39%) 
Pain in extremity † 1  8/123 (6.50%)  3/127 (2.36%)  11/144 (7.64%) 
Nervous system disorders       
Dizziness † 1  5/123 (4.07%)  4/127 (3.15%)  9/144 (6.25%) 
Headache † 1  5/123 (4.07%)  7/127 (5.51%)  12/144 (8.33%) 
Renal and urinary disorders       
Proteinuria † 1  11/123 (8.94%)  18/127 (14.17%)  19/144 (13.19%) 
Respiratory, thoracic and mediastinal disorders       
Cough † 1  9/123 (7.32%)  18/127 (14.17%)  15/144 (10.42%) 
Dyspnoea † 1  1/123 (0.81%)  9/127 (7.09%)  7/144 (4.86%) 
Oropharyngeal pain † 1  3/123 (2.44%)  6/127 (4.72%)  9/144 (6.25%) 
Skin and subcutaneous tissue disorders       
Acne † 1  1/123 (0.81%)  16/127 (12.60%)  3/144 (2.08%) 
Pruritus † 1  1/123 (0.81%)  7/127 (5.51%)  5/144 (3.47%) 
Rash † 1  1/123 (0.81%)  20/127 (15.75%)  12/144 (8.33%) 
Vascular disorders       
Hypertension † 1  5/123 (4.07%)  12/127 (9.45%)  8/144 (5.56%) 
Hypotension † 1  1/123 (0.81%)  7/127 (5.51%)  3/144 (2.08%) 
†
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA
[Not Specified]
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
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
Layout table for Results Point of Contact information
Name/Title: Study director
Organization: Novartis Pharmaceuticals
Phone: 862-778-8300
Layout table for additonal information
Responsible Party: Novartis ( Novartis Pharmaceuticals )
ClinicalTrials.gov Identifier: NCT00170846    
Other Study ID Numbers: CRAD001A2413
First Submitted: September 9, 2005
First Posted: September 15, 2005
Results First Submitted: December 17, 2010
Results First Posted: May 2, 2011
Last Update Posted: January 27, 2015