ASCERTAIN: Assessment of Everolimus in Addition to Calcineurin Inhibitor Reduction in the Maintenance of Renal Transplant Recipients
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00170846
Collaborator
(none)
394
1
3
56
7
Study Details
Study Description
Brief Summary
The study is designed to evaluate whether the initiation of everolimus together with the reduction or discontinuation of calcineurin inhibitors (CNIs) will improve graft function in the maintenance of renal transplant recipients with renal impairment by reducing the progression of chronic allograft nephropathy. The development of atherosclerosis in the native arteries of the patients will also be explored.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 4 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
394 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Assessment of Everolimus in Addition to Calcineurin Inhibitors Reduction in Maintenance Renal Transplant Recipients
Study Start Date
:
Feb 1, 2005
Actual Primary Completion Date
:
Oct 1, 2009
Actual Study Completion Date
:
Oct 1, 2009
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: Group A: No RAD Calcineurin Inhibitors (CNI) ± Mycophenolate Acid (MPA)/Azathioprine (AZA) ± Steroids |
Drug: Calcineurin Inhibitors (CNI)
Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
Drug: Steroids
|
| Experimental: Group B : CNI Withdrawal Initiation of everolimus (8-12 ng/mL) with discontinuation of CNI. Everolimus(RAD001) 4 mg initial daily dose. |
Drug: Everolimus (RAD001)
Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
Drug: Steroids
|
| Experimental: 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. |
Drug: Everolimus (RAD001)
Drug: Calcineurin Inhibitors (CNI)
Drug: Mycophenolate acid (MPA)/Azathioprine (AZA)
Drug: Steroids
|
Outcome Measures
Primary Outcome Measures
- Renal Function Assessed by Measured GFR (mGFR) [24 months]
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.
Secondary Outcome Measures
- Number of Participants With Safety Parameters [24 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Male or female patient at least 18 years of age.
-
Patient who has undergone a primary or secondary renal transplant 12-96 months ago from a living related or unrelated donor or a cadaveric donor.
-
Patient receiving cyclosporine microemulsion with a C2-h level ≥ 400 ng/mL or tacrolimus with a C0-h level ≥ 4 ng/mL with or without mycophenolic acid or azathioprine plus or minus steroids.
-
The immunosuppressive regimen must remain unchanged within the last 3 months.
-
Patient with renal impairment defined as GFR between 30 and 70 mL/min/1.73 m^2 by Cockcroft-Gault formula.
Exclusion Criteria:
-
Patient who is recipient of multiple organ transplants.
-
Patient with protein/creatinine ratio ≥ 150 (mg/mmol).
-
Patient with a treated acute rejection episode within the last 3 months.
-
Patient with any past or present BK-polyomavirus nephropathy.
-
Patient with de novo or recurrent glomerular nephritis.
Other protocol defined inclusion/exclusion criteria may apply.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis | Basel | Switzerland |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis, Novartis
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00170846
Other Study ID Numbers:
- CRAD001A2413
First Posted:
Sep 15, 2005
Last Update Posted:
Jan 27, 2015
Last Verified:
Mar 1, 2011
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Group A: No RAD | Group B : CNI Withdrawal | Group C: CNI Reduction |
|---|---|---|---|
| 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 |
Baseline Characteristics
| Arm/Group Title | Group A: No RAD | Group B : CNI Withdrawal | Group C: CNI Reduction | Total |
|---|---|---|---|---|
| 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 Participants | 123 | 127 | 144 | 394 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
48.2
(12.18)
|
49.4
(11.81)
|
49.7
(12.95)
|
49.1
(12.34)
|
| Sex: Female, Male (Count of 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 (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
5.8
(4.14)
|
5.4
(4.28)
|
5.4
(3.99)
|
5.6
(4.13)
|
Outcome Measures
| Title | Renal Function Assessed by Measured GFR (mGFR) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 103 | 94 | 109 |
| Mean (Standard Deviation) [mL/min/1.73m^2] |
46.02
(20.358)
|
48.00
(22.033)
|
46.60
(21.079)
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Group A: No RAD, Group B : CNI Withdrawal |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.6332 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS means |
| Estimated Value | 1.1241 | |
| Confidence Interval |
(2-Sided) 95% -3.5077 to 5.7559 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
Statistical Analysis 2
| Statistical Analysis Overview | Comparison Group Selection | Group A: No RAD, Group C: CNI Reduction |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.7943 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Difference in LS means |
| Estimated Value | 0.5933 | |
| Confidence Interval |
(2-Sided) 95% -3.8815 to 5.0682 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | Change in mGFR by Baseline Calculated Creatinine Clearance (Cockcroft-Gault Formula) |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 112 | 110 | 124 |
| 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)
|
| Title | Number of Participants With Safety Parameters |
|---|---|
| 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 |
Outcome Measure Data
| 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 |
|---|---|---|---|
| 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. |
| Measure Participants | 123 | 127 | 144 |
| Hypertension, Yes |
6
4.9%
|
13
10.2%
|
9
6.3%
|
| Hypertension, No |
117
95.1%
|
114
89.8%
|
135
93.8%
|
| Hyperlipidemia, Yes |
6
4.9%
|
18
14.2%
|
11
7.6%
|
| Hyperlipidemia, No |
117
95.1%
|
109
85.8%
|
133
92.4%
|
| Diabetes mellitus, Yes |
4
3.3%
|
6
4.7%
|
7
4.9%
|
| Diabetes mellitus, No |
119
96.7%
|
121
95.3%
|
137
95.1%
|
| Anemia, Yes |
25
20.3%
|
45
35.4%
|
46
31.9%
|
| Anemia, No |
98
79.7%
|
82
64.6%
|
98
68.1%
|
| Malignancies, Yes |
7
5.7%
|
9
7.1%
|
11
7.6%
|
| Malignancies, No |
116
94.3%
|
118
92.9%
|
133
92.4%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Group A: No RAD | Group B : CNI Withdrawal | Group C: CNI Reduction | |||
| 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 (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Group A: No RAD | Group B : CNI Withdrawal | Group C: CNI Reduction | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 52/123 (42.3%) | 72/127 (56.7%) | 78/144 (54.2%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 3/123 (2.4%) | 5/127 (3.9%) | 3/144 (2.1%) | |||
| Haemolytic uraemic syndrome | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Iron deficiency anaemia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Leukopenia | 0/123 (0%) | 2/127 (1.6%) | 0/144 (0%) | |||
| Lymphadenopathy | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Pancytopenia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Thrombocytopenia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cardiac disorders | ||||||
| Acute coronary syndrome | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Acute myocardial infarction | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Angina pectoris | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Aortic valve incompetence | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Atrial fibrillation | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Bradycardia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Cardiac arrest | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cardiac failure | 0/123 (0%) | 2/127 (1.6%) | 0/144 (0%) | |||
| Cardiac failure acute | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Cardiac failure congestive | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cardio-respiratory arrest | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Coronary artery stenosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Left ventricular failure | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Tachycardia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Ear and labyrinth disorders | ||||||
| Vertigo | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Eye disorders | ||||||
| Papilloedema | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Gastrointestinal disorders | ||||||
| Abdominal hernia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Abdominal pain | 0/123 (0%) | 1/127 (0.8%) | 3/144 (2.1%) | |||
| Abdominal pain upper | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Colitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Diarrhoea | 2/123 (1.6%) | 6/127 (4.7%) | 12/144 (8.3%) | |||
| Dysphagia | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Gastritis | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Gastritis erosive | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Gastrointestinal haemorrhage | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Gastrooesophageal reflux disease | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Glossodynia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Nausea | 0/123 (0%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Pancreatitis acute | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Peritoneal haemorrhage | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Peritonitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Reflux oesophagitis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Vomiting | 1/123 (0.8%) | 5/127 (3.9%) | 4/144 (2.8%) | |||
| General disorders | ||||||
| Asthenia | 0/123 (0%) | 0/127 (0%) | 3/144 (2.1%) | |||
| Chest discomfort | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Chest pain | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cyst | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Death | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Face oedema | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Localised oedema | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Non-cardiac chest pain | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Oedema peripheral | 1/123 (0.8%) | 1/127 (0.8%) | 3/144 (2.1%) | |||
| Pyrexia | 1/123 (0.8%) | 4/127 (3.1%) | 11/144 (7.6%) | |||
| Sudden death | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Hepatobiliary disorders | ||||||
| Cholecystitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Cholecystitis acute | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cholelithiasis | 0/123 (0%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Immune system disorders | ||||||
| Kidney transplant rejection | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Transplant rejection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Infections and infestations | ||||||
| Abdominal infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Abscess fungal | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Abscess neck | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Anal abscess | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Breast abscess | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Bronchiectasis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Bronchitis | 0/123 (0%) | 0/127 (0%) | 3/144 (2.1%) | |||
| Bronchitis viral | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Bronchopneumonia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Carbuncle | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Cardiac infection | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Catheter sepsis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Cellulitis | 2/123 (1.6%) | 3/127 (2.4%) | 4/144 (2.8%) | |||
| Cryptosporidiosis infection | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Cytomegalovirus infection | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Disseminated tuberculosis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Diverticulitis | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Endocarditis | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Enterocolitis infectious | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Escherichia infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Furuncle | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Gangrene | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Gastroenteritis | 5/123 (4.1%) | 4/127 (3.1%) | 6/144 (4.2%) | |||
| Hepatitis B | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Hepatitis E | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Herpes zoster | 0/123 (0%) | 2/127 (1.6%) | 1/144 (0.7%) | |||
| Infected sebaceous cyst | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Influenza | 0/123 (0%) | 2/127 (1.6%) | 0/144 (0%) | |||
| Lobar pneumonia | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Localised infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Lower respiratory tract infection | 1/123 (0.8%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Lower respiratory tract infection viral | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Lung infection | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Lung infection pseudomonal | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Meningitis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Mucormycosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Nail infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Nasopharyngitis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Oophoritis | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Oral infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Otitis media | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Perineal abscess | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Pneumonia | 5/123 (4.1%) | 2/127 (1.6%) | 6/144 (4.2%) | |||
| Pneumonia bacterial | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Postoperative wound infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Pulmonary tuberculosis | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Pyelonephritis | 0/123 (0%) | 1/127 (0.8%) | 5/144 (3.5%) | |||
| Pyelonephritis acute | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Respiratory tract infection | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Salmonella sepsis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Sepsis | 1/123 (0.8%) | 3/127 (2.4%) | 2/144 (1.4%) | |||
| Sialoadenitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Sinusitis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Skin infection | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Tooth abscess | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Tuberculosis bladder | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Tuberculosis of genitourinary system | 1/123 (0.8%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Upper respiratory tract infection | 0/123 (0%) | 4/127 (3.1%) | 1/144 (0.7%) | |||
| Urethral abscess | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Urinary tract infection | 6/123 (4.9%) | 5/127 (3.9%) | 10/144 (6.9%) | |||
| Urosepsis | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Varicella | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Viral infection | 1/123 (0.8%) | 2/127 (1.6%) | 1/144 (0.7%) | |||
| Wound infection | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| Arteriovenous fistula site complication | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Arteriovenous fistula thrombosis | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Chronic allograft nephropathy | 1/123 (0.8%) | 3/127 (2.4%) | 0/144 (0%) | |||
| Complications of transplanted kidney | 1/123 (0.8%) | 2/127 (1.6%) | 1/144 (0.7%) | |||
| Concussion | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Femur fracture | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Hand fracture | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Limb injury | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Muscle injury | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Post procedural complication | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Post procedural haematuria | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Postoperative wound complication | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Procedural vomiting | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Renal graft loss | 4/123 (3.3%) | 3/127 (2.4%) | 9/144 (6.3%) | |||
| Rib fracture | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Subdural haematoma | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase MB increased | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Blood creatine phosphokinase increased | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Blood creatinine increased | 7/123 (5.7%) | 7/127 (5.5%) | 4/144 (2.8%) | |||
| Blood folate decreased | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Blood urea increased | 1/123 (0.8%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Blood uric acid increased | 2/123 (1.6%) | 0/127 (0%) | 0/144 (0%) | |||
| Protein urine | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Tuberculin test positive | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Urine output decreased | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Vitamin B12 decreased | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Weight decreased | 0/123 (0%) | 2/127 (1.6%) | 1/144 (0.7%) | |||
| White blood cell count decreased | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Metabolism and nutrition disorders | ||||||
| Acidosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Decreased appetite | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Dehydration | 0/123 (0%) | 0/127 (0%) | 3/144 (2.1%) | |||
| Diabetes mellitus | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Diabetes mellitus inadequate control | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Fluid overload | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Gout | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Hypercalcaemia | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Hyperglycaemia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Hypocalcaemia | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Hypoglycaemia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Hypokalaemia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Hyponatraemia | 0/123 (0%) | 2/127 (1.6%) | 0/144 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Back pain | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Bursitis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Musculoskeletal chest pain | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Myositis ossificans | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Osteitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Osteonecrosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| Basal cell carcinoma | 1/123 (0.8%) | 2/127 (1.6%) | 4/144 (2.8%) | |||
| Basosquamous carcinoma of skin | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Benign uterine neoplasm | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Bowen's disease | 1/123 (0.8%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Breast cancer | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Lip neoplasm malignant stage unspecified | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Lung neoplasm malignant | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Malignant melanoma | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Metastatic malignant melanoma | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Prostate cancer | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Renal cell carcinoma | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Seborrhoeic keratosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Squamous cell carcinoma | 0/123 (0%) | 3/127 (2.4%) | 0/144 (0%) | |||
| Squamous cell carcinoma of skin | 1/123 (0.8%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Thyroid cancer | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Transitional cell carcinoma | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Uterine leiomyoma | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Nervous system disorders | ||||||
| Benign intracranial hypertension | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Brain stem infarction | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Cerebral infarction | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Convulsion | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Dizziness | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Headache | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Hemiplegia | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Ischaemic stroke | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Lethargy | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Loss of consciousness | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Nerve compression | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Partial seizures | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Syncope | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Tremor | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Vocal cord paralysis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Psychiatric disorders | ||||||
| Depression | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Renal and urinary disorders | ||||||
| Azotaemia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Glomerulonephritis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Haematuria | 2/123 (1.6%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Hydronephrosis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Nephrectasia | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Nephrotic syndrome | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Proteinuria | 1/123 (0.8%) | 3/127 (2.4%) | 0/144 (0%) | |||
| Renal failure | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Renal failure acute | 2/123 (1.6%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Renal impairment | 0/123 (0%) | 3/127 (2.4%) | 2/144 (1.4%) | |||
| Tubulointerstitial nephritis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Urethral obstruction | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Urinary bladder haemorrhage | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Vesicoureteric reflux | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Reproductive system and breast disorders | ||||||
| Amenorrhoea | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Endometriosis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Epididymitis | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Ovarian cyst | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Acute respiratory distress syndrome | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Bronchial disorder | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Chronic obstructive pulmonary disease | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Cough | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Dysphonia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Dyspnoea | 0/123 (0%) | 2/127 (1.6%) | 3/144 (2.1%) | |||
| Interstitial lung disease | 0/123 (0%) | 2/127 (1.6%) | 2/144 (1.4%) | |||
| Lung disorder | 1/123 (0.8%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Organising pneumonia | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Pneumonitis | 0/123 (0%) | 1/127 (0.8%) | 1/144 (0.7%) | |||
| Pulmonary congestion | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Pulmonary embolism | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Pulmonary oedema | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Tachypnoea | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Dermatitis contact | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Eczema | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Erythema | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Skin oedema | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Vascular disorders | ||||||
| Aortic aneurysm | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Arterial stenosis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Deep vein thrombosis | 0/123 (0%) | 0/127 (0%) | 2/144 (1.4%) | |||
| Extremity necrosis | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Haematoma | 0/123 (0%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Hypertension | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Hypertensive crisis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Hypotension | 0/123 (0%) | 0/127 (0%) | 1/144 (0.7%) | |||
| Iliac artery stenosis | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
| Peripheral vascular disorder | 2/123 (1.6%) | 1/127 (0.8%) | 0/144 (0%) | |||
| Varicose vein | 1/123 (0.8%) | 0/127 (0%) | 0/144 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Group A: No RAD | Group B : CNI Withdrawal | Group C: CNI Reduction | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 97/123 (78.9%) | 116/127 (91.3%) | 126/144 (87.5%) | |||
| Blood and lymphatic system disorders | ||||||
| Anaemia | 22/123 (17.9%) | 42/127 (33.1%) | 40/144 (27.8%) | |||
| Leukopenia | 5/123 (4.1%) | 10/127 (7.9%) | 3/144 (2.1%) | |||
| Thrombocytopenia | 1/123 (0.8%) | 10/127 (7.9%) | 4/144 (2.8%) | |||
| Gastrointestinal disorders | ||||||
| Aphthous stomatitis | 2/123 (1.6%) | 22/127 (17.3%) | 9/144 (6.3%) | |||
| Diarrhoea | 20/123 (16.3%) | 36/127 (28.3%) | 30/144 (20.8%) | |||
| Mouth ulceration | 1/123 (0.8%) | 15/127 (11.8%) | 8/144 (5.6%) | |||
| Nausea | 7/123 (5.7%) | 9/127 (7.1%) | 7/144 (4.9%) | |||
| Vomiting | 7/123 (5.7%) | 7/127 (5.5%) | 9/144 (6.3%) | |||
| General disorders | ||||||
| Oedema | 0/123 (0%) | 8/127 (6.3%) | 6/144 (4.2%) | |||
| Oedema peripheral | 12/123 (9.8%) | 33/127 (26%) | 37/144 (25.7%) | |||
| Pyrexia | 6/123 (4.9%) | 15/127 (11.8%) | 16/144 (11.1%) | |||
| Infections and infestations | ||||||
| Bronchitis | 7/123 (5.7%) | 6/127 (4.7%) | 6/144 (4.2%) | |||
| Nasopharyngitis | 8/123 (6.5%) | 9/127 (7.1%) | 13/144 (9%) | |||
| Upper respiratory tract infection | 16/123 (13%) | 11/127 (8.7%) | 15/144 (10.4%) | |||
| Urinary tract infection | 10/123 (8.1%) | 20/127 (15.7%) | 18/144 (12.5%) | |||
| Investigations | ||||||
| Blood creatine phosphokinase increased | 2/123 (1.6%) | 7/127 (5.5%) | 3/144 (2.1%) | |||
| Blood creatinine increased | 15/123 (12.2%) | 11/127 (8.7%) | 10/144 (6.9%) | |||
| Metabolism and nutrition disorders | ||||||
| Decreased appetite | 2/123 (1.6%) | 7/127 (5.5%) | 3/144 (2.1%) | |||
| Gout | 7/123 (5.7%) | 4/127 (3.1%) | 6/144 (4.2%) | |||
| Hypercholesterolaemia | 5/123 (4.1%) | 18/127 (14.2%) | 24/144 (16.7%) | |||
| Hyperlipidaemia | 6/123 (4.9%) | 18/127 (14.2%) | 11/144 (7.6%) | |||
| Hypertriglyceridaemia | 2/123 (1.6%) | 6/127 (4.7%) | 11/144 (7.6%) | |||
| Hypokalaemia | 3/123 (2.4%) | 12/127 (9.4%) | 1/144 (0.7%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| Arthralgia | 7/123 (5.7%) | 5/127 (3.9%) | 9/144 (6.3%) | |||
| Back pain | 7/123 (5.7%) | 1/127 (0.8%) | 2/144 (1.4%) | |||
| Pain in extremity | 8/123 (6.5%) | 3/127 (2.4%) | 11/144 (7.6%) | |||
| Nervous system disorders | ||||||
| Dizziness | 5/123 (4.1%) | 4/127 (3.1%) | 9/144 (6.3%) | |||
| Headache | 5/123 (4.1%) | 7/127 (5.5%) | 12/144 (8.3%) | |||
| Renal and urinary disorders | ||||||
| Proteinuria | 11/123 (8.9%) | 18/127 (14.2%) | 19/144 (13.2%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| Cough | 9/123 (7.3%) | 18/127 (14.2%) | 15/144 (10.4%) | |||
| Dyspnoea | 1/123 (0.8%) | 9/127 (7.1%) | 7/144 (4.9%) | |||
| Oropharyngeal pain | 3/123 (2.4%) | 6/127 (4.7%) | 9/144 (6.3%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| Acne | 1/123 (0.8%) | 16/127 (12.6%) | 3/144 (2.1%) | |||
| Pruritus | 1/123 (0.8%) | 7/127 (5.5%) | 5/144 (3.5%) | |||
| Rash | 1/123 (0.8%) | 20/127 (15.7%) | 12/144 (8.3%) | |||
| Vascular disorders | ||||||
| Hypertension | 5/123 (4.1%) | 12/127 (9.4%) | 8/144 (5.6%) | |||
| Hypotension | 1/123 (0.8%) | 7/127 (5.5%) | 3/144 (2.1%) | |||
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 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00170846
Other Study ID Numbers:
- CRAD001A2413
First Posted:
Sep 15, 2005
Last Update Posted:
Jan 27, 2015
Last Verified:
Mar 1, 2011