Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a Calcineurin Inhibitor (CNI)-Free Regimen and a CNI-low Dose Regimen
Sponsor
Novartis Pharmaceuticals (Industry)
Overall Status
Completed
CT.gov ID
NCT00514514
Collaborator
(none)
802
18
3
95
44.6
0.5
Study Details
Study Description
Brief Summary
The purpose of this study is to compare renal function of immunosuppressive regimens with different relevance of the calcineurin inhibitor (CNI) cyclosporine: standard dose CNI, low dose CNI, CNI free in de novo kidney transplant patients after 12 months of therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
802 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Multi-center, Open-label, Prospective, Randomized, Parallel Group, Long-term Study Investigating a Standard Regimen in de Novo Kidney Transplant Patients Versus a CNI-free Regimen and a CNI-low Dose Regimen
Study Start Date
:
Jul 1, 2007
Actual Primary Completion Date
:
Jun 1, 2015
Actual Study Completion Date
:
Jun 1, 2015
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Active Comparator: CNI standard regimen Myfortic, Sandimmun Optoral and corticosteroids |
Drug: Myfortic
1 tablet containing 180 mg or 360 mg
Dosing schedule:
Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen) According to blood level 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day)
Other Names:
Drug: Sandimmun Optoral
1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level
Other Names:
Drug: Simulect®
Lyophilisate in vials with ampoules of sterile water for injection (5 ml). Dosing: 1 vial containing 20 mg lyophilisate. Dosing schedule: 2 x 20 mg to be applied as 10 sec. bolus injection, i.v. on Day 0 (2 h before transplant) and on Day 4
Other Names:
|
| Experimental: CNI free regimen CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids |
Drug: Everolimus
Tablet containing 0.5 mg or 0.75 mg. Dosing schedule: Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen
Other Names:
Drug: Myfortic
1 tablet containing 180 mg or 360 mg
Dosing schedule:
Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen) According to blood level 1440 mg/day (2 x 720 mg), if tolerated. Dose reduction possible in case of side effects (min. dose at BL2 (Month 3): 720 mg/day)
Other Names:
Drug: Sandimmun Optoral
1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level
Other Names:
|
| Active Comparator: CNI low regimen CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
Drug: Everolimus
Tablet containing 0.5 mg or 0.75 mg. Dosing schedule: Initially 1.5 mg/day, then based on blood level (5-10 ng/mL in CNI free, 3-8 ng/mL in CNI low regimen
Other Names:
Drug: Sandimmun Optoral
1 capsule containing 10, 25, 50, or 100mg. Dosing: According to blood level
Other Names:
|
Outcome Measures
Primary Outcome Measures
- GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen [From randomization at BL2 (Month 3) to Month 12 post-transplant]
Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted
Secondary Outcome Measures
- GFR Via Nankivell Formula at Month 12 - All Regimens [From randomization at BL2 (Month 3) to Month 12 post-transplant]
Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
- GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method [From randomization at BL2 (Month 3) to Month 12 post-transplant]
Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
- GFR at Month 12 Utilizing Cockcroft-Gault Formula [From randomization at BL2 (Month 3) to Month 12 post-transplant]
Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
- Mean Change in Serum Creatinine From Month 3 to Month 12 [From randomization at BL2 (Month 3) to Month 12 post-transplant]
Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
- Efficacy Event Data From Baseline 2 (Month 3) to Month 6 [From Baseline 2 (Month 3) to Month 6]
Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
- Efficacy Event Data Baseline 2 (Month 3) to Month 12 [From Baseline 2 (Month 3) to Month 12]
Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
- Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk) [From Baseline 2 (Month 3) to Month 12]
The Framingham Score (based on LDL cholesterol level) estimates the coronary heart disease risk (%) of developing one of the following coronary heart diseases: angina pectoris, myocardial infarction, or coronary disease death, over the course of 10 years.
- GFR Calculated Via Nankivell Formula at Month 60 [From randomization at BL2 (Month 3) to Month 60]
Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
- GFR at Month 60 Utilizing Cockcroft-Gault Formula [From randomization at BL2 (Month 3) to Month 60 post-transplant]
Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl) For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
- GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method [From randomization at BL2 (Month 3) to Month 60 post-transplant]
Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate.
- Mean Change in Serum Creatinine From Month 3 to Month 60 [From randomization at BL2 (Month 3) to Month 60 post-transplant]
Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model
- Efficacy Event Data After Month 12 to Month 60 [Events starting after Month 12]
Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity).
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
to 70 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria
-
Males or females, aged 18 - 70 years
-
Recipients of de novo cadaveric, living unrelated or living related kidney transplants
-
Females capable of becoming pregnant must have a negative serum pregnancy test within 7 days prior to or at screening, and are required to practice an approved method of birth control for the duration of the study and for a period of 6 weeks following discontinuation of study medication, even where there has been a history of infertility.
-
Patients who are willing and able to participate in the study and from whom written informed consent has been obtained.
Exclusion criteria
-
More than one previous renal transplantation
-
Multi-organ recipients (e.g., kidney and pancreas) or previous transplant with any other organ, different from kidney
-
Patients receiving a kidney from a non-heart beating donor
-
Donor age: < 5 years or > 70 years
-
Graft loss due to immunological reasons in the first year after transplantation (in case of secondary transplantation)
-
Other protocol-defined inclusion/exclusion criteria may apply
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Novartis Investigative Site | Aachen | Germany | 52074 | |
| 2 | Novartis Investigative Site | Berlin | Germany | 10117 | |
| 3 | Novartis Investigative Site | Berlin | Germany | 13353 | |
| 4 | Novartis Investigative Site | Erlangen | Germany | 91054 | |
| 5 | Novartis Investigative Site | Essen | Germany | 45122 | |
| 6 | Novartis Investigative Site | Frankfurt am Main | Germany | 60596 | |
| 7 | Novartis Investigative Site | Freiburg | Germany | 79106 | |
| 8 | Novartis Investigative Site | Hamburg | Germany | 20246 | |
| 9 | Novartis Investigative Site | Hannover Muenden | Germany | 34346 | |
| 10 | Novartis Investigative Site | Hannover | Germany | 30625 | |
| 11 | Novartis Investigative Site | Heidelberg | Germany | 69120 | |
| 12 | Novartis Investigative Site | Kaiserslautern | Germany | 67655 | |
| 13 | Novartis Investigative Site | Koeln | Germany | 51109 | |
| 14 | Novartis Investigative Site | Lubeck | Germany | 23538 | |
| 15 | Novartis Investigative Site | Munchen | Germany | 81377 | |
| 16 | Novartis Investigative Site | München | Germany | 81675 | |
| 17 | Novartis Investigative Site | Regensburg | Germany | 93053 | |
| 18 | Novartis Investigative Site | Bern | Switzerland | 3010 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
- Study Director: Novartis, Novartis
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00514514
Other Study ID Numbers:
- CRAD001ADE13
- 2006-007021-32
First Posted:
Aug 10, 2007
Last Update Posted:
Jan 18, 2017
Last Verified:
Nov 1, 2016
Keywords provided by Novartis Pharmaceuticals
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | .817 patients were screened and 802 were enrolled on Day of transplant which served as Baseline Visit 1. For three months post transplantation, in the pre-phase period, all patients received induction therapy (Simulect®) and immunosuppressive therapy consisting of Myfortic, Sandimmun Optoral and corticosteroids. |
|---|---|
| Pre-assignment Detail | At month 3 post transplant, Baseline Visit 2, additional eligibility was assessed and patients randomized to one of 3 treatment arms and stratified according to kidney donor (living or cadaveric). |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Period Title: Pre-phase | |||
| STARTED | 802 | 0 | 0 |
| COMPLETED | 499 | 0 | 0 |
| NOT COMPLETED | 303 | 0 | 0 |
| Period Title: Pre-phase | |||
| STARTED | 166 | 171 | 162 |
| Randomized - Received Treatment | 165 | 171 | 161 |
| COMPLETED | 127 | 110 | 124 |
| NOT COMPLETED | 39 | 61 | 38 |
| Period Title: Pre-phase | |||
| STARTED | 145 | 139 | 134 |
| Non-randomized (Followed) | 95 | 0 | 0 |
| COMPLETED | 108 | 117 | 113 |
| NOT COMPLETED | 37 | 22 | 21 |
Baseline Characteristics
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen | Total |
|---|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids | Total of all reporting groups |
| Overall Participants | 165 | 171 | 161 | 497 |
| Age (years) [Mean (Standard Deviation) ] | ||||
| Mean (Standard Deviation) [years] |
49.9
(11.8)
|
48.9
(12.5)
|
48.6
(12.3)
|
49.1
(12.2)
|
| Gender (Count of Participants) | ||||
| Female |
65
39.4%
|
69
40.4%
|
61
37.9%
|
195
39.2%
|
| Male |
100
60.6%
|
102
59.6%
|
100
62.1%
|
302
60.8%
|
Outcome Measures
| Title | GFR Via Nankivell Method at Month 12 - CNI-Free vs Standard Regimen |
|---|---|
| Description | Demonstrate superiority of CNI-Free vs Standard Regimen in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. P-values are not adjusted |
| Time Frame | From randomization at BL2 (Month 3) to Month 12 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 159 | 163 | 160 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
63.03
|
68.59
|
63.08
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Standard Regimen, CNI Free Regimen |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | < 0.0001 |
| Comments | ||
| Method | ANCOVA | |
| Comments | ||
| Method of Estimation | Estimation Parameter | Mean Difference (Net) |
| Estimated Value | 5.56 | |
| Confidence Interval |
(2-Sided) 95% 2.82 to 8.31 |
|
| Parameter Dispersion |
Type: Value: |
|
| Estimation Comments | ||
| Title | GFR Via Nankivell Formula at Month 12 - All Regimens |
|---|---|
| Description | Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. |
| Time Frame | From randomization at BL2 (Month 3) to Month 12 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 159 | 163 | 160 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
63.03
|
68.59
|
63.08
|
| Title | GFR at Month 12 Utilizing Modification of Diet in Renal Disease (MDRD) Method |
|---|---|
| Description | Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. |
| Time Frame | From randomization at BL2 (Month 3) to Month 12 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 151 | 158 | 157 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
50.23
|
56.36
|
50.24
|
| Title | GFR at Month 12 Utilizing Cockcroft-Gault Formula |
|---|---|
| Description | Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl)For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Time Frame | From randomization at BL2 (Month 3) to Month 12 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 160 | 164 | 160 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
60.18
|
64.87
|
61.16
|
| Title | Mean Change in Serum Creatinine From Month 3 to Month 12 |
|---|---|
| Description | Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Time Frame | From randomization at BL2 (Month 3) to Month 12 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed required at least one post randomization value. ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 160 | 165 | 160 |
| Least Squares Mean (95% Confidence Interval) [mg/dl] |
1.66
|
1.58
|
1.76
|
| Title | Efficacy Event Data From Baseline 2 (Month 3) to Month 6 |
|---|---|
| Description | Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity). |
| Time Frame | From Baseline 2 (Month 3) to Month 6 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 165 | 171 | 161 |
| BPAR |
6
3.6%
|
15
8.8%
|
10
6.2%
|
| Graft loss |
0
0%
|
1
0.6%
|
1
0.6%
|
| Death |
1
0.6%
|
1
0.6%
|
0
0%
|
| Lost to follow-up |
0
0%
|
0
0%
|
0
0%
|
| Discontinuation due to lack of efficacy |
1
0.6%
|
2
1.2%
|
1
0.6%
|
| Discontinuation due to adverse event |
8
4.8%
|
26
15.2%
|
13
8.1%
|
| Therapy failure composite |
14
8.5%
|
37
21.6%
|
19
11.8%
|
| Title | Efficacy Event Data Baseline 2 (Month 3) to Month 12 |
|---|---|
| Description | Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity). |
| Time Frame | From Baseline 2 (Month 3) to Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 165 | 171 | 161 |
| BPAR |
13
7.9%
|
20
11.7%
|
13
8.1%
|
| Graft loss |
1
0.6%
|
2
1.2%
|
1
0.6%
|
| Death |
3
1.8%
|
2
1.2%
|
2
1.2%
|
| Lost to follow-up |
0
0%
|
0
0%
|
0
0%
|
| Discontinuation due to lack of efficacy |
2
1.2%
|
3
1.8%
|
1
0.6%
|
| Discontinuation due to adverse event |
25
15.2%
|
44
25.7%
|
27
16.8%
|
| Therapy failure composite |
34
20.6%
|
58
33.9%
|
35
21.7%
|
| Title | Change From BL2 (Month 3) to Month 12 in Cardiovascular Risk (Framingham Score; 10-year Cardiovascular Risk) |
|---|---|
| Description | The Framingham Score (based on LDL cholesterol level) estimates the coronary heart disease risk (%) of developing one of the following coronary heart diseases: angina pectoris, myocardial infarction, or coronary disease death, over the course of 10 years. |
| Time Frame | From Baseline 2 (Month 3) to Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 165 | 171 | 161 |
| Baseline 1/Visit 1 (n=165,171,161) |
10.9
(8)
|
10.2
(7.4)
|
9.5
(6.9)
|
| Baseline 2/Month 3 (n=165,171,161) |
10.3
(7.7)
|
8.8
(5.9)
|
9.3
(7.2)
|
| Month 12 (n=158,166,156) |
9.4
(6.8)
|
9.1
(6.4)
|
8.7
(6.8)
|
| Change from Baseline 2 to Month 12 (n=158,166,156) |
-0.7
(5.8)
|
0.4
(5.1)
|
-0.7
(5.4)
|
| Title | GFR Calculated Via Nankivell Formula at Month 60 |
|---|---|
| Description | Change in GFR using the Nankivell formula (GFR = 6.7 / Scr + BW / 4 - Surea / 2-100 / (height)² + C where where Scr is the serum creatinine concentration expressed in mmol/L, BW the body weight in kilograms, Surea the serum urea in mmol/L, height in m, and the constant C is 35 for male and 25 for female patients. The calculated GFR is expressed in mL/min per 1.73m², last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. |
| Time Frame | From randomization at BL2 (Month 3) to Month 60 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 99 | 108 | 104 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
60.24
|
66.98
|
58.74
|
| Title | GFR at Month 60 Utilizing Cockcroft-Gault Formula |
|---|---|
| Description | Cockcroft-Gault formula: For men: GFR= ((140-age) × body weight in kg)∕(72 x serum creatinine in mg∕dl) For women: GFR= (0.85×(140-age) × body weight in kg)∕(72 x serum creatinine in mg/dl), ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Time Frame | From randomization at BL2 (Month 3) to Month 60 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 162 | 165 | 159 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
55.92
|
61.6
|
52.91
|
| Title | GFR at Month 60 Utilizing Modification of Diet in Renal Disease (MDRD) Method |
|---|---|
| Description | Change in GFR (Modification of Diet in Renal Disease calculated using the -MDRD formulat: For men: GFR = 170 × (serum creatinine -0,999)×(age-0,176) x (urea nitrogen -0,17) × (albumin0,318) For women: GFR = 170 × (serum creatinine -0,999) × (age-0,176) × (urea nitrogen -0,17) x (albumin0,318) × 0.762 with urea nitrogen = urea / 2.144. ), last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model, with treatment, center, donor type (deceased vs. living) as factors and BL2-value at V4/M3/BL2 as covariate. |
| Time Frame | From randomization at BL2 (Month 3) to Month 60 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed differs due to different input values requested by the different formulas (Nankivell, MDRD and Cockcroft-Gault). ITT Population consisted of all patients who were randomized at Month 3 who received at least one dose of randomized treatment. The ITT population might have included patients without any data after randomization |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 152 | 159 | 156 |
| Least Squares Mean (95% Confidence Interval) [ml/min/1.73m²] |
47.56
|
53.41
|
44.79
|
| Title | Mean Change in Serum Creatinine From Month 3 to Month 60 |
|---|---|
| Description | Change in venous blood serum creatinine. Last observation carried forward (LOCF) was used for imputation of missing values, ANCOVA model |
| Time Frame | From randomization at BL2 (Month 3) to Month 60 post-transplant |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants analyzed were previously enrolled in the core study and had at least one serum creatinine value in the extension period. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 82 | 49 | 28 |
| Least Squares Mean (95% Confidence Interval) [mg/dl] |
1.94
|
1.69
|
2.01
|
| Title | Efficacy Event Data After Month 12 to Month 60 |
|---|---|
| Description | Efficacy events were: Biopsy-proven acute rejection (BPAR), graft loss, death, and treatment failure (defined as composite endpoint of BPAR, graft loss, death, loss to follow-up, discontinuation due to lack of efficacy or due to toxicity). |
| Time Frame | Events starting after Month 12 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The Intention-to-treat (ITT) Population consisted of all patients who were randomized at BL2 (Month 3), and who received at least one dose of randomized treatment. Patients were analyzed according to their assigned treatment. The ITT population might have included patients without any data after randomization. |
| Arm/Group Title | Standard Regimen | CNI Free Regimen | CNI Low Regimen |
|---|---|---|---|
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, everolimus 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, everolimus 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: everolimus 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: everolimus 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids |
| Measure Participants | 165 | 171 | 161 |
| BPAR |
13
7.9%
|
13
7.6%
|
12
7.5%
|
| Graft loss |
7
4.2%
|
7
4.1%
|
3
1.9%
|
| Death |
7
4.2%
|
4
2.3%
|
9
5.6%
|
| Lost to follow-up |
17
10.3%
|
15
8.8%
|
13
8.1%
|
| Discontinuation due to adverse event |
10
6.1%
|
8
4.7%
|
4
2.5%
|
| Therapy failure (composite endpoint) |
38
23%
|
35
20.5%
|
36
22.4%
|
Adverse Events
| Time Frame | ||||||
|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||
| Arm/Group Title | Standard Regimen | CNI-free | CNI-low | |||
| Arm/Group Description | Myfortic, Sandimmun Optoral and corticosteroids | CNI free regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Myfortic, Certican 1.5 mg, Sandimmun Optoral (50% of standard dose) and corticosteroids Step 2 at BL2 + 8 days: Myfortic, Certican 3 mg and corticosteroids | CNI low regimen: comprising the following steps for switching treatment: Step 1 at BL2 + 1 day: Certican 1.5 mg, Sandimmun Optoral and corticosteroids Step 2 at BL2 + 8 days: Certican 1.5 mg, Sandimmun Optoral (low dose) and corticosteroids | |||
All Cause Mortality |
||||||
| Standard Regimen | CNI-free | CNI-low | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | |||
Serious Adverse Events |
||||||
| Standard Regimen | CNI-free | CNI-low | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 87/165 (52.7%) | 91/171 (53.2%) | 85/161 (52.8%) | |||
| Blood and lymphatic system disorders | ||||||
| AGRANULOCYTOSIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| ANAEMIA | 1/165 (0.6%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| BONE MARROW OEDEMA | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| FEBRILE NEUTROPENIA | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| LEUKOPENIA | 0/165 (0%) | 4/171 (2.3%) | 1/161 (0.6%) | |||
| NEPHROGENIC ANAEMIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PANCYTOPENIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| POLYCYTHAEMIA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| THROMBOCYTOPENIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Cardiac disorders | ||||||
| ACUTE CORONARY SYNDROME | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| ANGINA PECTORIS | 2/165 (1.2%) | 0/171 (0%) | 0/161 (0%) | |||
| AORTIC VALVE STENOSIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| ATRIAL FIBRILLATION | 1/165 (0.6%) | 2/171 (1.2%) | 1/161 (0.6%) | |||
| ATRIAL FLUTTER | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| BRADYCARDIA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| CARDIAC FAILURE | 1/165 (0.6%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| CARDIAC FAILURE ACUTE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| CORONARY ARTERY DISEASE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Ear and labyrinth disorders | ||||||
| VERTIGO | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| Eye disorders | ||||||
| CATARACT | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| OPTIC ISCHAEMIC NEUROPATHY | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Gastrointestinal disorders | ||||||
| ASCITES | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| COLITIS | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| DIARRHOEA | 1/165 (0.6%) | 5/171 (2.9%) | 4/161 (2.5%) | |||
| GASTRITIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| GASTROINTESTINAL HAEMORRHAGE | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HAEMATOCHEZIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HAEMORRHOIDAL HAEMORRHAGE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| HAEMORRHOIDS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| NAUSEA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| NONINFECTIOUS PERITONITIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| RECTAL PERFORATION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| UPPER GASTROINTESTINAL HAEMORRHAGE | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| VOMITING | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| General disorders | ||||||
| ATROPHY | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| CHILLS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| DEVICE DISLOCATION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| GENERAL PHYSICAL HEALTH DETERIORATION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| GENERALISED OEDEMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| IMPAIRED HEALING | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| LOCALISED OEDEMA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| MULTI-ORGAN FAILURE | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| OEDEMA PERIPHERAL | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| PYREXIA | 1/165 (0.6%) | 3/171 (1.8%) | 4/161 (2.5%) | |||
| SUDDEN CARDIAC DEATH | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| Hepatobiliary disorders | ||||||
| CHOLECYSTITIS ACUTE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| CHOLELITHIASIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Immune system disorders | ||||||
| DRUG HYPERSENSITIVITY | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| KIDNEY TRANSPLANT REJECTION | 5/165 (3%) | 6/171 (3.5%) | 4/161 (2.5%) | |||
| TRANSPLANT REJECTION | 6/165 (3.6%) | 13/171 (7.6%) | 9/161 (5.6%) | |||
| Infections and infestations | ||||||
| ANORECTAL INFECTION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| APPENDICITIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| ATYPICAL PNEUMONIA | 2/165 (1.2%) | 1/171 (0.6%) | 0/161 (0%) | |||
| BK VIRUS INFECTION | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| BRONCHITIS | 2/165 (1.2%) | 0/171 (0%) | 1/161 (0.6%) | |||
| BRONCHOPNEUMONIA | 1/165 (0.6%) | 0/171 (0%) | 2/161 (1.2%) | |||
| CANDIDA INFECTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| CYSTITIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| CYTOMEGALOVIRUS GASTROENTERITIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| CYTOMEGALOVIRUS INFECTION | 6/165 (3.6%) | 1/171 (0.6%) | 4/161 (2.5%) | |||
| CYTOMEGALOVIRUS VIRAEMIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| DIABETIC GANGRENE | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| DIARRHOEA INFECTIOUS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| ENCEPHALITIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| EPSTEIN-BARR VIRUS INFECTION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| ESCHERICHIA INFECTION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| FEBRILE INFECTION | 1/165 (0.6%) | 0/171 (0%) | 2/161 (1.2%) | |||
| GANGRENE | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| GASTROENTERITIS | 3/165 (1.8%) | 6/171 (3.5%) | 2/161 (1.2%) | |||
| GASTROENTERITIS NOROVIRUS | 1/165 (0.6%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| GASTROINTESTINAL INFECTION | 0/165 (0%) | 1/171 (0.6%) | 2/161 (1.2%) | |||
| GROIN ABSCESS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HAEMATOMA INFECTION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HERPES ZOSTER | 2/165 (1.2%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| INFECTION | 4/165 (2.4%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| INFLUENZA | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| KIDNEY INFECTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| LOWER RESPIRATORY TRACT INFECTION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| NECROTISING FASCIITIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PNEUMOCYSTIS JIROVECII PNEUMONIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PNEUMONIA | 3/165 (1.8%) | 6/171 (3.5%) | 4/161 (2.5%) | |||
| PNEUMONIA CYTOMEGALOVIRAL | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| PNEUMONIA INFLUENZAL | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PNEUMONIA STREPTOCOCCAL | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PSEUDOMEMBRANOUS COLITIS | 0/165 (0%) | 0/171 (0%) | 2/161 (1.2%) | |||
| PYELONEPHRITIS | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PYONEPHROSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| RENAL CYST INFECTION | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| RESPIRATORY TRACT INFECTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SALPINGO-OOPHORITIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SEPSIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| SEPTIC SHOCK | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| SHUNT INFECTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SINUSITIS | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| STAPHYLOCOCCAL INFECTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| URINARY TRACT INFECTION | 15/165 (9.1%) | 12/171 (7%) | 7/161 (4.3%) | |||
| UROSEPSIS | 6/165 (3.6%) | 2/171 (1.2%) | 7/161 (4.3%) | |||
| VARICELLA | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| VIRAL INFECTION | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| WOUND INFECTION | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Injury, poisoning and procedural complications | ||||||
| ACCIDENT | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| ANKLE FRACTURE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| COMPLICATIONS OF TRANSPLANT SURGERY | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| COMPLICATIONS OF TRANSPLANTED KIDNEY | 5/165 (3%) | 0/171 (0%) | 2/161 (1.2%) | |||
| CONTUSION | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| FEMORAL NECK FRACTURE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| FIBULA FRACTURE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| GRAFT LOSS | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| HEAT STROKE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| INCISIONAL HERNIA | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| KIDNEY RUPTURE | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| OVERDOSE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| POST PROCEDURAL HAEMORRHAGE | 2/165 (1.2%) | 0/171 (0%) | 0/161 (0%) | |||
| RENAL LYMPHOCELE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SEROMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SHUNT OCCLUSION | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| TIBIA FRACTURE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| TOXICITY TO VARIOUS AGENTS | 2/165 (1.2%) | 0/171 (0%) | 1/161 (0.6%) | |||
| TRANSPLANT DYSFUNCTION | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| TRANSPLANT FAILURE | 3/165 (1.8%) | 5/171 (2.9%) | 3/161 (1.9%) | |||
| TRAUMATIC HAEMATOMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| VENA CAVA INJURY | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Investigations | ||||||
| BLOOD CREATININE INCREASED | 14/165 (8.5%) | 14/171 (8.2%) | 17/161 (10.6%) | |||
| CARBOHYDRATE ANTIGEN 125 INCREASED | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| CREATININE URINE INCREASED | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| CYTOMEGALOVIRUS TEST | 2/165 (1.2%) | 0/171 (0%) | 0/161 (0%) | |||
| CYTOMEGALOVIRUS TEST POSITIVE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| HAEMOGLOBIN DECREASED | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HEPATIC ENZYME INCREASED | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| IMMUNOSUPPRESSANT DRUG LEVEL INCREASED | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| RED BLOOD CELL ACANTHOCYTES PRESENT | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| WEIGHT INCREASED | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Metabolism and nutrition disorders | ||||||
| DEHYDRATION | 0/165 (0%) | 1/171 (0.6%) | 2/161 (1.2%) | |||
| DIABETES MELLITUS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HYPOCALCAEMIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HYPOGLYCAEMIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| TUMOUR LYSIS SYNDROME | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| TYPE 2 DIABETES MELLITUS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHROPATHY | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| JOINT SWELLING | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| MUSCULAR WEAKNESS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| MYALGIA | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| MYOSITIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| NEUROPATHIC ARTHROPATHY | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| OSTEONECROSIS | 2/165 (1.2%) | 0/171 (0%) | 2/161 (1.2%) | |||
| POST TRANSPLANT DISTAL LIMB SYNDROME | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| RHABDOMYOLYSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||
| B-CELL LYMPHOMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| BASAL CELL CARCINOMA | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| BRONCHIAL CARCINOMA | 1/165 (0.6%) | 1/171 (0.6%) | 0/161 (0%) | |||
| CLEAR CELL RENAL CELL CARCINOMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| LIPOMA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| METASTASES TO LIVER | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| OVARIAN CANCER | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| POST TRANSPLANT LYMPHOPROLIFERATIVE DISORDER | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| RENAL CELL CARCINOMA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| SKIN PAPILLOMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| SQUAMOUS CELL CARCINOMA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| Nervous system disorders | ||||||
| APHASIA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| CEREBRAL INFARCTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| CEREBROVASCULAR ACCIDENT | 1/165 (0.6%) | 2/171 (1.2%) | 0/161 (0%) | |||
| HEADACHE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| HEMIPARESIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| POLYNEUROPATHY | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PRESYNCOPE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Psychiatric disorders | ||||||
| ADJUSTMENT DISORDER | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| DEPRESSION | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PANIC ATTACK | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| RESTLESSNESS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| Renal and urinary disorders | ||||||
| ACUTE KIDNEY INJURY | 0/165 (0%) | 1/171 (0.6%) | 2/161 (1.2%) | |||
| GLOMERULOSCLEROSIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| HAEMATURIA | 2/165 (1.2%) | 0/171 (0%) | 1/161 (0.6%) | |||
| HYDRONEPHROSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| KIDNEY FIBROSIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| NEPHRECTASIA | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| NEPHROLITHIASIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| NEPHROPATHY | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PROTEINURIA | 0/165 (0%) | 3/171 (1.8%) | 1/161 (0.6%) | |||
| REFLUX NEPHROPATHY | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| RENAL ARTERY STENOSIS | 2/165 (1.2%) | 2/171 (1.2%) | 0/161 (0%) | |||
| RENAL CYST RUPTURED | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| RENAL FAILURE | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| RENAL IMPAIRMENT | 2/165 (1.2%) | 0/171 (0%) | 0/161 (0%) | |||
| RENAL INFARCT | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| RENAL TUBULAR ATROPHY | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| TUBULOINTERSTITIAL NEPHRITIS | 0/165 (0%) | 0/171 (0%) | 2/161 (1.2%) | |||
| URETERIC STENOSIS | 2/165 (1.2%) | 1/171 (0.6%) | 0/161 (0%) | |||
| URETHRAL OBSTRUCTION | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| URETHRAL STENOSIS | 2/165 (1.2%) | 1/171 (0.6%) | 0/161 (0%) | |||
| URINARY RETENTION | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| URINARY TRACT OBSTRUCTION | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| VESICOURETERIC REFLUX | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Reproductive system and breast disorders | ||||||
| OVARIAN CYST | 0/165 (0%) | 2/171 (1.2%) | 0/161 (0%) | |||
| VAGINAL HAEMORRHAGE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| ALVEOLITIS ALLERGIC | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| DYSPNOEA | 2/165 (1.2%) | 3/171 (1.8%) | 0/161 (0%) | |||
| PLEURAL FIBROSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PLEURISY | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| PRODUCTIVE COUGH | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| PULMONARY EMBOLISM | 0/165 (0%) | 2/171 (1.2%) | 2/161 (1.2%) | |||
| PULMONARY OEDEMA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| SLEEP APNOEA SYNDROME | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| Skin and subcutaneous tissue disorders | ||||||
| SKIN ULCER | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Surgical and medical procedures | ||||||
| RESUSCITATION | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| Vascular disorders | ||||||
| ARTERIAL HAEMORRHAGE | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| ARTERIAL THROMBOSIS | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| ARTERIOSCLEROSIS | 0/165 (0%) | 2/171 (1.2%) | 1/161 (0.6%) | |||
| ARTERIOVENOUS FISTULA | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| DEEP VEIN THROMBOSIS | 1/165 (0.6%) | 0/171 (0%) | 1/161 (0.6%) | |||
| EMBOLISM | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| EMBOLISM ARTERIAL | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| HYPERTENSION | 0/165 (0%) | 1/171 (0.6%) | 1/161 (0.6%) | |||
| HYPERTENSIVE CRISIS | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| LYMPHOCELE | 2/165 (1.2%) | 1/171 (0.6%) | 4/161 (2.5%) | |||
| LYMPHOEDEMA | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| PERIPHERAL ARTERY STENOSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| THROMBOPHLEBITIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| THROMBOSIS | 0/165 (0%) | 0/171 (0%) | 3/161 (1.9%) | |||
| VASCULITIS | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
| VENOUS ANEURYSM | 1/165 (0.6%) | 0/171 (0%) | 0/161 (0%) | |||
| VENOUS OCCLUSION | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| VENOUS THROMBOSIS | 0/165 (0%) | 0/171 (0%) | 1/161 (0.6%) | |||
| VENOUS THROMBOSIS LIMB | 0/165 (0%) | 1/171 (0.6%) | 0/161 (0%) | |||
Other (Not Including Serious) Adverse Events |
||||||
| Standard Regimen | CNI-free | CNI-low | ||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 121/165 (73.3%) | 134/171 (78.4%) | 133/161 (82.6%) | |||
| Blood and lymphatic system disorders | ||||||
| ANAEMIA | 5/165 (3%) | 14/171 (8.2%) | 2/161 (1.2%) | |||
| LEUKOPENIA | 22/165 (13.3%) | 26/171 (15.2%) | 18/161 (11.2%) | |||
| Gastrointestinal disorders | ||||||
| APHTHOUS STOMATITIS | 1/165 (0.6%) | 33/171 (19.3%) | 14/161 (8.7%) | |||
| DIARRHOEA | 17/165 (10.3%) | 34/171 (19.9%) | 15/161 (9.3%) | |||
| NAUSEA | 5/165 (3%) | 8/171 (4.7%) | 9/161 (5.6%) | |||
| General disorders | ||||||
| OEDEMA | 15/165 (9.1%) | 14/171 (8.2%) | 22/161 (13.7%) | |||
| OEDEMA PERIPHERAL | 9/165 (5.5%) | 17/171 (9.9%) | 28/161 (17.4%) | |||
| Infections and infestations | ||||||
| CYTOMEGALOVIRUS INFECTION | 12/165 (7.3%) | 8/171 (4.7%) | 4/161 (2.5%) | |||
| NASOPHARYNGITIS | 29/165 (17.6%) | 36/171 (21.1%) | 37/161 (23%) | |||
| URINARY TRACT INFECTION | 37/165 (22.4%) | 31/171 (18.1%) | 32/161 (19.9%) | |||
| Investigations | ||||||
| BLOOD CREATININE INCREASED | 14/165 (8.5%) | 11/171 (6.4%) | 12/161 (7.5%) | |||
| Metabolism and nutrition disorders | ||||||
| HYPERCHOLESTEROLAEMIA | 4/165 (2.4%) | 8/171 (4.7%) | 18/161 (11.2%) | |||
| HYPERLIPIDAEMIA | 4/165 (2.4%) | 6/171 (3.5%) | 11/161 (6.8%) | |||
| HYPERURICAEMIA | 9/165 (5.5%) | 3/171 (1.8%) | 4/161 (2.5%) | |||
| HYPOKALAEMIA | 10/165 (6.1%) | 20/171 (11.7%) | 6/161 (3.7%) | |||
| IRON DEFICIENCY | 10/165 (6.1%) | 7/171 (4.1%) | 7/161 (4.3%) | |||
| Musculoskeletal and connective tissue disorders | ||||||
| ARTHRALGIA | 2/165 (1.2%) | 11/171 (6.4%) | 7/161 (4.3%) | |||
| Nervous system disorders | ||||||
| HEADACHE | 7/165 (4.2%) | 11/171 (6.4%) | 10/161 (6.2%) | |||
| Renal and urinary disorders | ||||||
| PROTEINURIA | 3/165 (1.8%) | 6/171 (3.5%) | 13/161 (8.1%) | |||
| Respiratory, thoracic and mediastinal disorders | ||||||
| COUGH | 11/165 (6.7%) | 8/171 (4.7%) | 7/161 (4.3%) | |||
| Vascular disorders | ||||||
| HYPERTENSION | 10/165 (6.1%) | 5/171 (2.9%) | 10/161 (6.2%) | |||
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 or disclosure of trial results in their entirety.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Novartis |
| Phone | 862-778-8300 |
Responsible Party:
Novartis Pharmaceuticals
ClinicalTrials.gov Identifier:
NCT00514514
Other Study ID Numbers:
- CRAD001ADE13
- 2006-007021-32
First Posted:
Aug 10, 2007
Last Update Posted:
Jan 18, 2017
Last Verified:
Nov 1, 2016