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Trial Outcomes & Findings for ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin Inhibitor Reduction in the Maintenance of Renal Transplant Recipients (NCT NCT00170846)

NCT ID: NCT00170846

Last Updated: 2015-01-27

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

394 participants

Primary outcome timeframe

24 months

Results posted on

2015-01-27

Participant Flow

Participant milestones

Participant milestones
Measure
Group A: No RAD
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Overall Study
STARTED
123
127
144
Overall Study
COMPLETED
112
108
131
Overall Study
NOT COMPLETED
11
19
13

Reasons for withdrawal

Reasons for withdrawal
Measure
Group A: No RAD
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Overall Study
Subject withdrew Informed Consent
5
12
8
Overall Study
Lost to Follow-up
6
3
2
Overall Study
Death
0
3
3
Overall Study
Reason Missing
0
1
0

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Group A: No RAD
n=123 Participants
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=127 Participants
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=144 Participants
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Total
n=394 Participants
Total of all reporting groups
Age, Continuous
48.2 years
STANDARD_DEVIATION 12.18 • n=5 Participants
49.4 years
STANDARD_DEVIATION 11.81 • n=7 Participants
49.7 years
STANDARD_DEVIATION 12.95 • n=5 Participants
49.1 years
STANDARD_DEVIATION 12.34 • n=4 Participants
Sex: Female, Male
Female
41 Participants
n=5 Participants
41 Participants
n=7 Participants
53 Participants
n=5 Participants
135 Participants
n=4 Participants
Sex: Female, Male
Male
82 Participants
n=5 Participants
86 Participants
n=7 Participants
91 Participants
n=5 Participants
259 Participants
n=4 Participants
Time since transplantation
5.8 years
STANDARD_DEVIATION 4.14 • n=5 Participants
5.4 years
STANDARD_DEVIATION 4.28 • n=7 Participants
5.4 years
STANDARD_DEVIATION 3.99 • n=5 Participants
5.6 years
STANDARD_DEVIATION 4.13 • n=4 Participants

PRIMARY outcome

Timeframe: 24 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Group A: No RAD
n=103 Participants
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=94 Participants
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=109 Participants
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Renal Function Assessed by Measured GFR (mGFR)
46.02 mL/min/1.73m^2
Standard Deviation 20.358
48.00 mL/min/1.73m^2
Standard Deviation 22.033
46.60 mL/min/1.73m^2
Standard Deviation 21.079

SECONDARY outcome

Timeframe: 24 months

Population: 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.

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.

Outcome measures

Outcome measures
Measure
Group A: No RAD
n=123 Participants
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=127 Participants
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=144 Participants
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Number of Participants With Safety Parameters
Hypertension, Yes
6 Participants
13 Participants
9 Participants
Number of Participants With Safety Parameters
Hypertension, No
117 Participants
114 Participants
135 Participants
Number of Participants With Safety Parameters
Hyperlipidemia, Yes
6 Participants
18 Participants
11 Participants
Number of Participants With Safety Parameters
Hyperlipidemia, No
117 Participants
109 Participants
133 Participants
Number of Participants With Safety Parameters
Diabetes mellitus, Yes
4 Participants
6 Participants
7 Participants
Number of Participants With Safety Parameters
Diabetes mellitus, No
119 Participants
121 Participants
137 Participants
Number of Participants With Safety Parameters
Anemia, Yes
25 Participants
45 Participants
46 Participants
Number of Participants With Safety Parameters
Anemia, No
98 Participants
82 Participants
98 Participants
Number of Participants With Safety Parameters
Malignancies, Yes
7 Participants
9 Participants
11 Participants
Number of Participants With Safety Parameters
Malignancies, No
116 Participants
118 Participants
133 Participants

POST_HOC outcome

Timeframe: Baseline and 24 months

Population: 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.

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 \[mg/dL\]

Outcome measures

Outcome measures
Measure
Group A: No RAD
n=112 Participants
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=110 Participants
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=124 Participants
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Change in mGFR by Baseline Calculated Creatinine Clearance (Cockcroft-Gault Formula)
Baseline CrCl(CG) ≤ 50 :(n= 32, 28, 32):- Change
1.55 mL/min
Standard Deviation 12.833
-5.75 mL/min
Standard Deviation 14.712
0.82 mL/min
Standard Deviation 19.445
Change in mGFR by Baseline Calculated Creatinine Clearance (Cockcroft-Gault Formula)
Baseline CrCl(CG) > 50 : (n=31, 29, 39):-Change
-2.55 mL/min
Standard Deviation 19.562
7.32 mL/min
Standard Deviation 21.051
-0.24 mL/min
Standard Deviation 17.551

Adverse Events

Group A: No RAD

Serious events: 52 serious events
Other events: 97 other events
Deaths: 0 deaths

Group B : CNI Withdrawal

Serious events: 72 serious events
Other events: 116 other events
Deaths: 0 deaths

Group C: CNI Reduction

Serious events: 78 serious events
Other events: 126 other events
Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure
Group A: No RAD
n=123 participants at risk
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=127 participants at risk
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=144 participants at risk
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Blood and lymphatic system disorders
Anaemia
2.4%
3/123
3.9%
5/127
2.1%
3/144
Blood and lymphatic system disorders
Haemolytic uraemic syndrome
0.00%
0/123
0.79%
1/127
0.69%
1/144
Blood and lymphatic system disorders
Iron deficiency anaemia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Blood and lymphatic system disorders
Leukopenia
0.00%
0/123
1.6%
2/127
0.00%
0/144
Blood and lymphatic system disorders
Lymphadenopathy
0.00%
0/123
0.00%
0/127
0.69%
1/144
Blood and lymphatic system disorders
Pancytopenia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Blood and lymphatic system disorders
Thrombocytopenia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Cardiac disorders
Acute coronary syndrome
0.00%
0/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Acute myocardial infarction
0.00%
0/123
0.00%
0/127
1.4%
2/144
Cardiac disorders
Angina pectoris
0.81%
1/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Aortic valve incompetence
0.00%
0/123
0.79%
1/127
0.00%
0/144
Cardiac disorders
Atrial fibrillation
0.00%
0/123
0.00%
0/127
1.4%
2/144
Cardiac disorders
Bradycardia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Cardiac arrest
0.00%
0/123
0.79%
1/127
0.00%
0/144
Cardiac disorders
Cardiac failure
0.00%
0/123
1.6%
2/127
0.00%
0/144
Cardiac disorders
Cardiac failure acute
0.81%
1/123
0.00%
0/127
0.00%
0/144
Cardiac disorders
Cardiac failure congestive
0.00%
0/123
0.79%
1/127
0.00%
0/144
Cardiac disorders
Cardio-respiratory arrest
0.00%
0/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Coronary artery stenosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Left ventricular failure
0.00%
0/123
0.00%
0/127
0.69%
1/144
Cardiac disorders
Tachycardia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Ear and labyrinth disorders
Vertigo
0.81%
1/123
0.00%
0/127
0.00%
0/144
Eye disorders
Papilloedema
0.81%
1/123
0.00%
0/127
0.00%
0/144
Gastrointestinal disorders
Abdominal hernia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Gastrointestinal disorders
Abdominal pain
0.00%
0/123
0.79%
1/127
2.1%
3/144
Gastrointestinal disorders
Abdominal pain upper
0.00%
0/123
0.00%
0/127
1.4%
2/144
Gastrointestinal disorders
Colitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Gastrointestinal disorders
Diarrhoea
1.6%
2/123
4.7%
6/127
8.3%
12/144
Gastrointestinal disorders
Dysphagia
0.00%
0/123
0.79%
1/127
0.69%
1/144
Gastrointestinal disorders
Gastritis
0.81%
1/123
0.00%
0/127
0.69%
1/144
Gastrointestinal disorders
Gastritis erosive
0.81%
1/123
0.00%
0/127
0.00%
0/144
Gastrointestinal disorders
Gastrointestinal haemorrhage
0.00%
0/123
0.00%
0/127
1.4%
2/144
Gastrointestinal disorders
Gastrooesophageal reflux disease
0.81%
1/123
0.00%
0/127
0.00%
0/144
Gastrointestinal disorders
Glossodynia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Gastrointestinal disorders
Nausea
0.00%
0/123
0.79%
1/127
1.4%
2/144
Gastrointestinal disorders
Pancreatitis acute
0.00%
0/123
0.00%
0/127
1.4%
2/144
Gastrointestinal disorders
Peritoneal haemorrhage
0.81%
1/123
0.00%
0/127
0.00%
0/144
Gastrointestinal disorders
Peritonitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Gastrointestinal disorders
Reflux oesophagitis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Gastrointestinal disorders
Vomiting
0.81%
1/123
3.9%
5/127
2.8%
4/144
General disorders
Asthenia
0.00%
0/123
0.00%
0/127
2.1%
3/144
General disorders
Chest discomfort
0.81%
1/123
0.00%
0/127
0.00%
0/144
General disorders
Chest pain
0.00%
0/123
0.79%
1/127
0.00%
0/144
General disorders
Cyst
0.00%
0/123
0.79%
1/127
0.00%
0/144
General disorders
Death
0.00%
0/123
0.79%
1/127
0.00%
0/144
General disorders
Face oedema
0.00%
0/123
0.00%
0/127
0.69%
1/144
General disorders
Localised oedema
0.00%
0/123
0.79%
1/127
0.00%
0/144
General disorders
Non-cardiac chest pain
0.00%
0/123
0.00%
0/127
0.69%
1/144
General disorders
Oedema peripheral
0.81%
1/123
0.79%
1/127
2.1%
3/144
General disorders
Pyrexia
0.81%
1/123
3.1%
4/127
7.6%
11/144
General disorders
Sudden death
0.00%
0/123
0.79%
1/127
0.00%
0/144
Hepatobiliary disorders
Cholecystitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Hepatobiliary disorders
Cholecystitis acute
0.00%
0/123
0.79%
1/127
0.00%
0/144
Hepatobiliary disorders
Cholelithiasis
0.00%
0/123
0.79%
1/127
1.4%
2/144
Immune system disorders
Kidney transplant rejection
0.00%
0/123
0.00%
0/127
0.69%
1/144
Immune system disorders
Transplant rejection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Abdominal infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Abscess fungal
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Abscess neck
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Anal abscess
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Breast abscess
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Bronchiectasis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Bronchitis
0.00%
0/123
0.00%
0/127
2.1%
3/144
Infections and infestations
Bronchitis viral
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Bronchopneumonia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Carbuncle
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Cardiac infection
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Catheter sepsis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Cellulitis
1.6%
2/123
2.4%
3/127
2.8%
4/144
Infections and infestations
Cryptosporidiosis infection
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Cytomegalovirus infection
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Disseminated tuberculosis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Diverticulitis
0.00%
0/123
0.00%
0/127
1.4%
2/144
Infections and infestations
Endocarditis
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Enterocolitis infectious
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Escherichia infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Furuncle
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Gangrene
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Gastroenteritis
4.1%
5/123
3.1%
4/127
4.2%
6/144
Infections and infestations
Hepatitis B
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Hepatitis E
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Herpes zoster
0.00%
0/123
1.6%
2/127
0.69%
1/144
Infections and infestations
Infected sebaceous cyst
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Influenza
0.00%
0/123
1.6%
2/127
0.00%
0/144
Infections and infestations
Lobar pneumonia
0.00%
0/123
0.00%
0/127
1.4%
2/144
Infections and infestations
Localised infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Lower respiratory tract infection
0.81%
1/123
0.79%
1/127
1.4%
2/144
Infections and infestations
Lower respiratory tract infection viral
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Lung infection
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Lung infection pseudomonal
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Meningitis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Mucormycosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Nail infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Nasopharyngitis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Oophoritis
0.00%
0/123
0.00%
0/127
1.4%
2/144
Infections and infestations
Oral infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Otitis media
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Perineal abscess
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Pneumonia
4.1%
5/123
1.6%
2/127
4.2%
6/144
Infections and infestations
Pneumonia bacterial
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Postoperative wound infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Pulmonary tuberculosis
0.81%
1/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Pyelonephritis
0.00%
0/123
0.79%
1/127
3.5%
5/144
Infections and infestations
Pyelonephritis acute
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Respiratory tract infection
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Salmonella sepsis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Sepsis
0.81%
1/123
2.4%
3/127
1.4%
2/144
Infections and infestations
Sialoadenitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Sinusitis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Skin infection
0.00%
0/123
0.00%
0/127
0.69%
1/144
Infections and infestations
Tooth abscess
0.00%
0/123
0.00%
0/127
1.4%
2/144
Infections and infestations
Tuberculosis bladder
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Tuberculosis of genitourinary system
0.81%
1/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Upper respiratory tract infection
0.00%
0/123
3.1%
4/127
0.69%
1/144
Infections and infestations
Urethral abscess
0.00%
0/123
0.79%
1/127
0.00%
0/144
Infections and infestations
Urinary tract infection
4.9%
6/123
3.9%
5/127
6.9%
10/144
Infections and infestations
Urosepsis
0.00%
0/123
0.79%
1/127
0.69%
1/144
Infections and infestations
Varicella
0.81%
1/123
0.00%
0/127
0.00%
0/144
Infections and infestations
Viral infection
0.81%
1/123
1.6%
2/127
0.69%
1/144
Infections and infestations
Wound infection
0.00%
0/123
0.79%
1/127
0.00%
0/144
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
0.00%
0/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
0.00%
0/123
0.79%
1/127
0.69%
1/144
Injury, poisoning and procedural complications
Chronic allograft nephropathy
0.81%
1/123
2.4%
3/127
0.00%
0/144
Injury, poisoning and procedural complications
Complications of transplanted kidney
0.81%
1/123
1.6%
2/127
0.69%
1/144
Injury, poisoning and procedural complications
Concussion
0.00%
0/123
0.79%
1/127
0.00%
0/144
Injury, poisoning and procedural complications
Femur fracture
0.00%
0/123
0.79%
1/127
0.00%
0/144
Injury, poisoning and procedural complications
Hand fracture
0.00%
0/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Limb injury
0.00%
0/123
0.79%
1/127
0.00%
0/144
Injury, poisoning and procedural complications
Muscle injury
0.00%
0/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Post procedural complication
0.00%
0/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Post procedural haematuria
0.00%
0/123
0.79%
1/127
0.69%
1/144
Injury, poisoning and procedural complications
Postoperative wound complication
0.81%
1/123
0.00%
0/127
0.00%
0/144
Injury, poisoning and procedural complications
Procedural vomiting
0.00%
0/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Renal graft loss
3.3%
4/123
2.4%
3/127
6.2%
9/144
Injury, poisoning and procedural complications
Rib fracture
0.81%
1/123
0.00%
0/127
0.69%
1/144
Injury, poisoning and procedural complications
Subdural haematoma
0.00%
0/123
0.79%
1/127
0.00%
0/144
Investigations
Blood creatine phosphokinase MB increased
0.00%
0/123
0.00%
0/127
0.69%
1/144
Investigations
Blood creatine phosphokinase increased
0.00%
0/123
0.00%
0/127
0.69%
1/144
Investigations
Blood creatinine increased
5.7%
7/123
5.5%
7/127
2.8%
4/144
Investigations
Blood folate decreased
0.81%
1/123
0.00%
0/127
0.00%
0/144
Investigations
Blood urea increased
0.81%
1/123
0.79%
1/127
0.00%
0/144
Investigations
Blood uric acid increased
1.6%
2/123
0.00%
0/127
0.00%
0/144
Investigations
Protein urine
0.00%
0/123
0.00%
0/127
0.69%
1/144
Investigations
Tuberculin test positive
0.81%
1/123
0.00%
0/127
0.00%
0/144
Investigations
Urine output decreased
0.00%
0/123
0.00%
0/127
0.69%
1/144
Investigations
Vitamin B12 decreased
0.81%
1/123
0.00%
0/127
0.00%
0/144
Investigations
Weight decreased
0.00%
0/123
1.6%
2/127
0.69%
1/144
Investigations
White blood cell count decreased
0.00%
0/123
0.79%
1/127
0.00%
0/144
Metabolism and nutrition disorders
Acidosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Metabolism and nutrition disorders
Decreased appetite
0.00%
0/123
0.00%
0/127
1.4%
2/144
Metabolism and nutrition disorders
Dehydration
0.00%
0/123
0.00%
0/127
2.1%
3/144
Metabolism and nutrition disorders
Diabetes mellitus
0.00%
0/123
0.79%
1/127
0.69%
1/144
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
0.00%
0/123
0.79%
1/127
0.69%
1/144
Metabolism and nutrition disorders
Fluid overload
0.00%
0/123
0.00%
0/127
0.69%
1/144
Metabolism and nutrition disorders
Gout
0.00%
0/123
0.00%
0/127
0.69%
1/144
Metabolism and nutrition disorders
Hypercalcaemia
0.81%
1/123
0.00%
0/127
0.69%
1/144
Metabolism and nutrition disorders
Hyperglycaemia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Metabolism and nutrition disorders
Hypocalcaemia
0.81%
1/123
0.00%
0/127
0.00%
0/144
Metabolism and nutrition disorders
Hypoglycaemia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Metabolism and nutrition disorders
Hypokalaemia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Metabolism and nutrition disorders
Hyponatraemia
0.00%
0/123
1.6%
2/127
0.00%
0/144
Musculoskeletal and connective tissue disorders
Arthralgia
0.00%
0/123
0.00%
0/127
1.4%
2/144
Musculoskeletal and connective tissue disorders
Back pain
0.00%
0/123
0.79%
1/127
0.00%
0/144
Musculoskeletal and connective tissue disorders
Bursitis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Musculoskeletal and connective tissue disorders
Musculoskeletal chest pain
0.81%
1/123
0.00%
0/127
0.69%
1/144
Musculoskeletal and connective tissue disorders
Myositis ossificans
0.00%
0/123
0.79%
1/127
0.00%
0/144
Musculoskeletal and connective tissue disorders
Osteitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Musculoskeletal and connective tissue disorders
Osteonecrosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma
0.81%
1/123
1.6%
2/127
2.8%
4/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basosquamous carcinoma of skin
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Benign uterine neoplasm
0.81%
1/123
0.00%
0/127
0.00%
0/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Bowen's disease
0.81%
1/123
0.00%
0/127
1.4%
2/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast cancer
0.00%
0/123
0.79%
1/127
0.00%
0/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lip neoplasm malignant stage unspecified
0.81%
1/123
0.00%
0/127
0.00%
0/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Lung neoplasm malignant
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Malignant melanoma
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Metastatic malignant melanoma
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Prostate cancer
0.00%
0/123
0.79%
1/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cell carcinoma
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Seborrhoeic keratosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma
0.00%
0/123
2.4%
3/127
0.00%
0/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Squamous cell carcinoma of skin
0.81%
1/123
0.79%
1/127
1.4%
2/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Thyroid cancer
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Transitional cell carcinoma
0.00%
0/123
0.00%
0/127
0.69%
1/144
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Uterine leiomyoma
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Benign intracranial hypertension
0.81%
1/123
0.00%
0/127
0.00%
0/144
Nervous system disorders
Brain stem infarction
0.81%
1/123
0.00%
0/127
0.00%
0/144
Nervous system disorders
Cerebral infarction
0.81%
1/123
0.00%
0/127
0.00%
0/144
Nervous system disorders
Convulsion
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Dizziness
0.00%
0/123
0.79%
1/127
0.00%
0/144
Nervous system disorders
Headache
0.81%
1/123
0.00%
0/127
0.00%
0/144
Nervous system disorders
Hemiplegia
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Ischaemic stroke
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Lethargy
0.00%
0/123
0.79%
1/127
0.69%
1/144
Nervous system disorders
Loss of consciousness
0.00%
0/123
0.79%
1/127
0.00%
0/144
Nervous system disorders
Nerve compression
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Partial seizures
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Syncope
0.00%
0/123
0.00%
0/127
0.69%
1/144
Nervous system disorders
Tremor
0.00%
0/123
0.79%
1/127
0.00%
0/144
Nervous system disorders
Vocal cord paralysis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Psychiatric disorders
Depression
0.81%
1/123
0.00%
0/127
0.00%
0/144
Renal and urinary disorders
Azotaemia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Glomerulonephritis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Haematuria
1.6%
2/123
0.79%
1/127
1.4%
2/144
Renal and urinary disorders
Hydronephrosis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Nephrectasia
0.81%
1/123
0.00%
0/127
0.00%
0/144
Renal and urinary disorders
Nephrotic syndrome
0.00%
0/123
0.00%
0/127
0.69%
1/144
Renal and urinary disorders
Proteinuria
0.81%
1/123
2.4%
3/127
0.00%
0/144
Renal and urinary disorders
Renal failure
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Renal failure acute
1.6%
2/123
0.79%
1/127
0.69%
1/144
Renal and urinary disorders
Renal impairment
0.00%
0/123
2.4%
3/127
1.4%
2/144
Renal and urinary disorders
Tubulointerstitial nephritis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Urethral obstruction
0.00%
0/123
0.79%
1/127
0.00%
0/144
Renal and urinary disorders
Urinary bladder haemorrhage
0.00%
0/123
0.00%
0/127
0.69%
1/144
Renal and urinary disorders
Vesicoureteric reflux
0.00%
0/123
0.79%
1/127
0.00%
0/144
Reproductive system and breast disorders
Amenorrhoea
0.00%
0/123
0.00%
0/127
0.69%
1/144
Reproductive system and breast disorders
Endometriosis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Reproductive system and breast disorders
Epididymitis
0.00%
0/123
0.00%
0/127
0.69%
1/144
Reproductive system and breast disorders
Ovarian cyst
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Bronchial disorder
0.00%
0/123
0.79%
1/127
0.00%
0/144
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Cough
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Dysphonia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.00%
0/123
1.6%
2/127
2.1%
3/144
Respiratory, thoracic and mediastinal disorders
Interstitial lung disease
0.00%
0/123
1.6%
2/127
1.4%
2/144
Respiratory, thoracic and mediastinal disorders
Lung disorder
0.81%
1/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Organising pneumonia
0.00%
0/123
0.79%
1/127
0.00%
0/144
Respiratory, thoracic and mediastinal disorders
Pneumonitis
0.00%
0/123
0.79%
1/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Pulmonary congestion
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
0.00%
0/123
0.00%
0/127
1.4%
2/144
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
0.00%
0/123
0.00%
0/127
0.69%
1/144
Respiratory, thoracic and mediastinal disorders
Tachypnoea
0.00%
0/123
0.00%
0/127
0.69%
1/144
Skin and subcutaneous tissue disorders
Dermatitis contact
0.00%
0/123
0.79%
1/127
0.00%
0/144
Skin and subcutaneous tissue disorders
Eczema
0.00%
0/123
0.79%
1/127
0.00%
0/144
Skin and subcutaneous tissue disorders
Erythema
0.00%
0/123
0.79%
1/127
0.00%
0/144
Skin and subcutaneous tissue disorders
Skin oedema
0.00%
0/123
0.00%
0/127
0.69%
1/144
Vascular disorders
Aortic aneurysm
0.00%
0/123
0.00%
0/127
0.69%
1/144
Vascular disorders
Arterial stenosis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Vascular disorders
Deep vein thrombosis
0.00%
0/123
0.00%
0/127
1.4%
2/144
Vascular disorders
Extremity necrosis
0.00%
0/123
0.79%
1/127
0.00%
0/144
Vascular disorders
Haematoma
0.00%
0/123
0.79%
1/127
0.00%
0/144
Vascular disorders
Hypertension
0.00%
0/123
0.00%
0/127
0.69%
1/144
Vascular disorders
Hypertensive crisis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Vascular disorders
Hypotension
0.00%
0/123
0.00%
0/127
0.69%
1/144
Vascular disorders
Iliac artery stenosis
0.81%
1/123
0.00%
0/127
0.00%
0/144
Vascular disorders
Peripheral vascular disorder
1.6%
2/123
0.79%
1/127
0.00%
0/144
Vascular disorders
Varicose vein
0.81%
1/123
0.00%
0/127
0.00%
0/144

Other adverse events

Other adverse events
Measure
Group A: No RAD
n=123 participants at risk
Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids
Group B : CNI Withdrawal
n=127 participants at risk
Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus (RAD001) 4 mg initial daily dose.
Group C: CNI Reduction
n=144 participants at risk
Initiation of everolimus (3-8 ng/mL) with reduction by 70-90% in CNI blood levels. Everolimus (RAD001) 3 mg initial daily dose.
Blood and lymphatic system disorders
Anaemia
17.9%
22/123
33.1%
42/127
27.8%
40/144
Blood and lymphatic system disorders
Leukopenia
4.1%
5/123
7.9%
10/127
2.1%
3/144
Blood and lymphatic system disorders
Thrombocytopenia
0.81%
1/123
7.9%
10/127
2.8%
4/144
Gastrointestinal disorders
Aphthous stomatitis
1.6%
2/123
17.3%
22/127
6.2%
9/144
Gastrointestinal disorders
Diarrhoea
16.3%
20/123
28.3%
36/127
20.8%
30/144
Gastrointestinal disorders
Mouth ulceration
0.81%
1/123
11.8%
15/127
5.6%
8/144
Gastrointestinal disorders
Nausea
5.7%
7/123
7.1%
9/127
4.9%
7/144
Gastrointestinal disorders
Vomiting
5.7%
7/123
5.5%
7/127
6.2%
9/144
General disorders
Oedema
0.00%
0/123
6.3%
8/127
4.2%
6/144
General disorders
Oedema peripheral
9.8%
12/123
26.0%
33/127
25.7%
37/144
General disorders
Pyrexia
4.9%
6/123
11.8%
15/127
11.1%
16/144
Infections and infestations
Bronchitis
5.7%
7/123
4.7%
6/127
4.2%
6/144
Infections and infestations
Nasopharyngitis
6.5%
8/123
7.1%
9/127
9.0%
13/144
Infections and infestations
Upper respiratory tract infection
13.0%
16/123
8.7%
11/127
10.4%
15/144
Infections and infestations
Urinary tract infection
8.1%
10/123
15.7%
20/127
12.5%
18/144
Investigations
Blood creatine phosphokinase increased
1.6%
2/123
5.5%
7/127
2.1%
3/144
Investigations
Blood creatinine increased
12.2%
15/123
8.7%
11/127
6.9%
10/144
Metabolism and nutrition disorders
Decreased appetite
1.6%
2/123
5.5%
7/127
2.1%
3/144
Metabolism and nutrition disorders
Gout
5.7%
7/123
3.1%
4/127
4.2%
6/144
Metabolism and nutrition disorders
Hypercholesterolaemia
4.1%
5/123
14.2%
18/127
16.7%
24/144
Metabolism and nutrition disorders
Hyperlipidaemia
4.9%
6/123
14.2%
18/127
7.6%
11/144
Metabolism and nutrition disorders
Hypertriglyceridaemia
1.6%
2/123
4.7%
6/127
7.6%
11/144
Metabolism and nutrition disorders
Hypokalaemia
2.4%
3/123
9.4%
12/127
0.69%
1/144
Musculoskeletal and connective tissue disorders
Arthralgia
5.7%
7/123
3.9%
5/127
6.2%
9/144
Musculoskeletal and connective tissue disorders
Back pain
5.7%
7/123
0.79%
1/127
1.4%
2/144
Musculoskeletal and connective tissue disorders
Pain in extremity
6.5%
8/123
2.4%
3/127
7.6%
11/144
Nervous system disorders
Dizziness
4.1%
5/123
3.1%
4/127
6.2%
9/144
Nervous system disorders
Headache
4.1%
5/123
5.5%
7/127
8.3%
12/144
Renal and urinary disorders
Proteinuria
8.9%
11/123
14.2%
18/127
13.2%
19/144
Respiratory, thoracic and mediastinal disorders
Cough
7.3%
9/123
14.2%
18/127
10.4%
15/144
Respiratory, thoracic and mediastinal disorders
Dyspnoea
0.81%
1/123
7.1%
9/127
4.9%
7/144
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
2.4%
3/123
4.7%
6/127
6.2%
9/144
Skin and subcutaneous tissue disorders
Acne
0.81%
1/123
12.6%
16/127
2.1%
3/144
Skin and subcutaneous tissue disorders
Pruritus
0.81%
1/123
5.5%
7/127
3.5%
5/144
Skin and subcutaneous tissue disorders
Rash
0.81%
1/123
15.7%
20/127
8.3%
12/144
Vascular disorders
Hypertension
4.1%
5/123
9.4%
12/127
5.6%
8/144
Vascular disorders
Hypotension
0.81%
1/123
5.5%
7/127
2.1%
3/144

Additional Information

Study director

Novartis Pharmaceuticals

Phone: 862-778-8300

Results disclosure agreements

  • Principal investigator is a sponsor employee 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.
  • Publication restrictions are in place

Restriction type: OTHER