NOCTET: Nordic Everolimus (Certican) Trial in Heart and Lung Transplantation
Study Details
Study Description
Brief Summary
This study investigated whether initiation of everolimus together with reduction of calcineurin inhibitors (CNI) in maintenance heart or lung transplant patients with renal impairment would improve renal function.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 4 |
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Everolimus + CNI reduction Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice. |
Drug: Everolimus
0.75-1.5 mg twice daily. At the week 1 visit and thereafter, the dose was adjusted to target blood concentration in the range 3-8 ng/mL.
Other Names:
Drug: Calcineurin inhibitors (CNI)
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
Drug: Steroids
Steroid treatment was according to local practice. If steroids were given, the baseline dose of prednisone or equivalent was to be kept unchanged for all treatment groups for the total study duration, unless a medical condition dictated a change.
|
Active Comparator: Control CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Drug: Mycophenolic acid (MPA)/azathioprine (AZA)
In the standard CNI arm, all immunosuppressants including (MPA) and azathioprine (AZA) continued unchanged as per local practice.
Other Names:
Drug: Calcineurin inhibitors (CNI)
Calcineurin inhibitors include cyclosporine, pimecrolimus, and tacrolimus.
Drug: Steroids
Steroid treatment was according to local practice. If steroids were given, the baseline dose of prednisone or equivalent was to be kept unchanged for all treatment groups for the total study duration, unless a medical condition dictated a change.
|
Outcome Measures
Primary Outcome Measures
- Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 [Baseline to Month 12]
Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.
Secondary Outcome Measures
- Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) [Baseline to end of study (Month 24)]
Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function.
- Change in Serum Creatinine From Baseline to End of Study (Month 24) [Baseline to end of study (Month 24)]
Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function.
- Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) [Month 12 to end of study (Month 24)]
Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart & Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy.
- Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) [Month 12 to end of study (Month 24)]
Number of patients not alive and number of patients with loss of their graft.
- Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) [Month 12 to end of study (Month 24)]
- Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup [Baseline to end of study (Month 24)]
Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function.
- Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup [Baseline to end of study (Month 24)]
Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function.
- Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup [Baseline to end of study (Month 24)]
Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function.
- Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup [Baseline to end of study (Month 24)]
Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function.
- Mean Days of Hospitalization From Baseline to End of Study (Month 24) [Baseline to end of study (Month 24)]
- Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) [Month 12 to end of study (Month 24)]
Eligibility Criteria
Criteria
Inclusion criteria:
-
Patients who have undergone a heart or lung transplantation more than 12 months ago.
-
Patients receiving Neoral® or Prograf®.
-
Patients with a measured or calculated glomerular filtration rate (GFR) > 20 and < 70 mL/min/1.73m2. For patients with a GFR > 60 and < 70 mL/min/1.73m2, a deteriorated renal function since the time of transplantation must be documented by at least one post-transplant GFR level that is > 10% above the GFR level at the time of inclusion.
-
Patients willing and capable of giving written informed consent for study participation and able to participate in the study for 12 months.
-
Females of potential childbearing age must have a negative serum pregnancy test within 7 days prior to enrollment. Effective contraception must be used during the trial and for 6 weeks following discontinuation of the study medication, even where there has been a history of infertility.
Exclusion criteria:
-
Patients who are recipients of multiple organ transplants.
-
Patients with measured GFR < 20 mL/min/1.73m2 or > 70 mL/min/1.73m2.
-
Patients with a treated acute rejection episode within the last 3 months.
-
Patients with a platelet count of < 50,000/mm3 or with a white blood cell count of ≤ 2,500/mm3 or with a hemoglobin value < 8 g/dL.
-
Presence of severe hypercholesterolemia (≥ 8.0 mmol/L) or hypertriglyceridemia (≥ 6.0 mmol/L) despite conventional lipid lowering treatment.
-
Patients currently treated or who have been treated with a mammalian target of rapamycin (mTOR) inhibitor.
-
Patients who have received an investigational drug within 4 weeks.
-
Patients who are human immunodeficiency virus positive or who have a current severe systemic infection requiring continued therapy according to investigator judgment.
-
Present use of any immunosuppressive drugs other than Neoral®/Prograf®, mycophenolic acid/azathioprine (MPA/AZA), and/or steroids.
-
Patients with a known hypersensitivity to drugs similar to everolimus.
-
Symptoms of significant mental illness which, in the opinion of the investigator, may interfere with the patient's ability to comply with the protocol. History of drug or alcohol abuse within 1 year of baseline.
-
Inability to cooperate or communicate with the investigator.
-
Patients with any past (within the last 5 years) or present malignancy other than excised squamous or basal cell carcinoma.
-
Females of childbearing potential that are planning to become pregnant, who are pregnant and/or lactating, or who are unwilling to use effective means of contraception.
-
Patients with a planned coronary revascularization or patients who have experienced a major adverse cardiovascular event (MACE) within the last 3 months.
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | Novartis Investigative Site | Arhus | Denmark | DK-8200 | |
2 | Novartis Investigative Site | Copenhagen | Denmark | 2100 | |
3 | Novartis Investigative Site | Oslo | Norway | ||
4 | Novartis Investigative Site | Goteborg | Sweden | 413 45 | |
5 | Novartis Investigative Site | Linkoping | Sweden | 581 85 | |
6 | Novartis Investigative Site | Lund | Sweden | 22185 |
Sponsors and Collaborators
- Novartis Pharmaceuticals
Investigators
- Study Director: Novartis Pharmaceuticals, Novartis Pharmaceuticals
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CRAD001AIC01
Study Results
Participant Flow
Recruitment Details | This was a 12-month study in maintenance heart and lung transplant patients with a follow-up period of an additional 12 months. Results to 24 months are presented. Patients were randomized to continue their current calcineurin inhibitors (CNI) based regimen or to start everolimus with reduction of CNI blood levels. |
---|---|
Pre-assignment Detail |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Period Title: Core Study: 0-12 Months | ||
STARTED | 140 | 142 |
COMPLETED | 112 | 133 |
NOT COMPLETED | 28 | 9 |
Period Title: Core Study: 0-12 Months | ||
STARTED | 108 | 127 |
COMPLETED | 98 | 123 |
NOT COMPLETED | 10 | 4 |
Baseline Characteristics
Arm/Group Title | Everolimus + CNI Reduction | Control | Total |
---|---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | Total of all reporting groups |
Overall Participants | 140 | 142 | 282 |
Age (years) [Mean (Standard Deviation) ] | |||
Mean (Standard Deviation) [years] |
59.2
(9.5)
|
56.4
(10.7)
|
57.8
(9.96)
|
Sex: Female, Male (Count of Participants) | |||
Female |
37
26.4%
|
40
28.2%
|
77
27.3%
|
Male |
103
73.6%
|
102
71.8%
|
205
72.7%
|
Outcome Measures
Title | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to Month 12 |
---|---|
Description | Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function. |
Time Frame | Baseline to Month 12 |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 114 | 132 |
Baseline |
48.6
(15.1)
|
48.0
(13.2)
|
Month 12 |
53.2
(15.7)
|
47.5
(16.1)
|
Change from Baseline |
4.6
(10.4)
|
-0.5
(9.0)
|
Title | Change in Measured Glomerular Filtration Rate (mGFR) From Baseline to End of Study (Month 24) |
---|---|
Description | Renal function was assessed by determining the measured glomerular filtration rate (mGFR) using creatinine ethylenediamine tetraacetic acid (Cr-EDTA) clearance or an equivalent method. A positive change score indicates improved renal function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 103 | 119 |
Month 0 |
49.3
(14.7)
|
49.1
(13.0)
|
Month 24 |
52.5
(16.4)
|
46.8
(15.2)
|
Change |
3.2
(12.3)
|
-2.4
(9.0)
|
Title | Change in Serum Creatinine From Baseline to End of Study (Month 24) |
---|---|
Description | Renal function was assessed by determining serum creatinine using standard laboratory methods. A positive change score indicates improved renal function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 114 | 132 |
Month 0 |
126
(30)
|
129
(29)
|
Month 24 |
126
(64)
|
132
(37)
|
Change |
0
(53)
|
3
(23)
|
Title | Number of Patients With Biopsy-proven Acute Rejection From Month 12 to End of Study (Month 24) |
---|---|
Description | Biopsy-proved acute rejection was defined as a treated acute rejection confirmed by biopsy, graded locally according to the International Society for Heart & Lung Transplantation (ISHLT) criteria. A treated acute rejection was defined as an acute rejection clinically suspected, whether biopsy-proven or not, which had been treated and confirmed by the investigator according to the response to therapy. |
Time Frame | Month 12 to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 108 | 127 |
Number [Participants] |
6
4.3%
|
5
3.5%
|
Title | Number of Patients Who Died and Number of Patients With Graft Loss From Month 12 to End of Study (Month 24) |
---|---|
Description | Number of patients not alive and number of patients with loss of their graft. |
Time Frame | Month 12 to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 108 | 127 |
Death |
3
2.1%
|
0
0%
|
Graft Loss |
0
0%
|
0
0%
|
Title | Number of Patients in Need of Dialysis From Month 12 to End of Study (Month 24) |
---|---|
Description | |
Time Frame | Month 12 to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
The intent-to-treat (ITT) population consisted of all patients as randomized, who were given at least one dose of study drug and had at least one post-baseline assessment. (Extension study) |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 108 | 127 |
Number [Participants] |
0
0%
|
2
1.4%
|
Title | Change in Forced Expiratory Volume in 1 Second (FEV1) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup |
---|---|
Description | Forced expiratory volume in 1 second (FEV1) was measured by spirometry conducted according to internationally accepted standards. FEV1 is the volume delivered in the first second of a forced vital capacity (FVC) maneuver. A positive change score indicates improved lung function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the lung transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 36 | 40 |
Mean (Standard Deviation) [Liters] |
-0.2
(0.2)
|
-0.1
(0.2)
|
Title | Change in Forced Vital Capacity (FVC) From Baseline to End of Study (Month 24) in the Lung Transplant Subgroup |
---|---|
Description | Forced vital capacity (FVC) was measured by spirometry conducted according to internationally accepted standards. FVC is the volume delivered during an expiration made as forcefully and completely as possible starting from full inspiration. A positive change score indicates improved lung function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the lung transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 36 | 40 |
Mean (Standard Deviation) [Liters] |
-0.2
(0.3)
|
-0.1
(0.4)
|
Title | Change in Left Ventricular Function (Diameter and Thickness Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup |
---|---|
Description | Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were left ventricular end diastolic diameter (LVEDD), left ventricular end systolic diameter (LVESD), interventricular septal wall thickness (IVSTd), and posterior wall thickness (PWTd). A positive change score indicates improved left ventricular function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the heart transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 56 | 73 |
LVEDD |
-0.1
(0.8)
|
-0.0
(0.4)
|
LVESD |
0.1
(0.7)
|
0.1
(0.6)
|
IVSTd |
-0.4
(2.4)
|
-0.1
(1.2)
|
PWTd |
-0.5
(2.1)
|
-0.1
(1.1)
|
Title | Change in Left Ventricular Function (Filling and Ejection Fraction Parameters) From Baseline to End of Study (Month 24) in the Heart Transplant Subgroup |
---|---|
Description | Left ventricular function was assessed by echocardiography which was performed according to local routine practice. Echocardiography parameters were filling fraction (FF) and ejection fraction (EF). A positive change score indicates improved left ventricular function. |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Patients in the heart transplant subgroup of the intent-to-treat (ITT) population which included all randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 59 | 71 |
EF |
-0.6
(8.5)
|
0.1
(7.9)
|
FF |
0
(1)
|
0
(1)
|
Title | Mean Days of Hospitalization From Baseline to End of Study (Month 24) |
---|---|
Description | |
Time Frame | Baseline to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 108 | 127 |
Mean (Standard Deviation) [Days] |
8.5
(7.4)
|
16.2
(19.3)
|
Title | Number of Patients Discontinued From the Study Due to Adverse Events From Month 12 to End of Study (Month 24) |
---|---|
Description | |
Time Frame | Month 12 to end of study (Month 24) |
Outcome Measure Data
Analysis Population Description |
---|
Intent-to-treat (ITT) population: All randomized patients who were given at least 1 dose of study drug and had at least 1 post-baseline assessment. |
Arm/Group Title | Everolimus + CNI Reduction | Control |
---|---|---|
Arm/Group Description | Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%,upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice | CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. |
Measure Participants | 108 | 127 |
Total discontinued due to AE(s) |
8
5.7%
|
0
0%
|
Pulmonary embolism |
2
1.4%
|
0
0%
|
Skin problems |
1
0.7%
|
0
0%
|
Hypercholesterolemia |
1
0.7%
|
0
0%
|
Stroke |
1
0.7%
|
0
0%
|
Muscular pain |
1
0.7%
|
0
0%
|
Diarrhea |
1
0.7%
|
0
0%
|
Edema |
1
0.7%
|
0
0%
|
Adverse Events
Time Frame | 24 months | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Adverse Event Reporting Description | Safety population stratified by sub groups (heart patients and lung patients) and duration of core study and extension study. | |||||||||||||||
Arm/Group Title | Control: 12 Month Heart | Everolimus + CNI Reduction: 12 Month Heart | Control: 12 Month Lung | Everolimus+CNI Reduction: 12 Month Lung | Control: 24 Month Heart | Everolimus + CNI Reduction: 24 Month Heart | Control: 24 Month Lung | Everolimus + CNI Reduction: 24 Month Lung | ||||||||
Arm/Group Description | Subgroup of "Control" group with heart patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | Subgroup of "everolimus + CNI reduction" group with heart patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice. | Subgroup of "control" group with lung patients at 12 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | Subgroup of "everolimus + CNI reduction" group with lung patients at 12 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice. | Subgroup of "Control" group with heart patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | Subgroup of "everolimus + CNI reduction" group with heart patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice. | Subgroup of "Control" group with lung patients at 24 months. CNI ± MPA/AZA ± steroids. In the standard CNI arm, all immunosuppressants including mycophenolic acid (MPA) and azathioprine (AZA) continued unchanged as per local practice. Steroid treatment was according to local practice. | Subgroup of "everolimus + CNI reduction" group with lung patients at 24 months. Everolimus (3-8 ng/mL) + CNI reduction ± MPA/AZA ± steroids. Everolimus 0.75-1.5 mg twice daily. Dose adjusted to target blood concentration in the range 3-8 ng/mL. CNI reduction (reduced 50-70%): target of achieving a cyclosporine A (CsA) trough level < 75 ng/mL or a tacrolimus trough level < 4 ng/mL. MPA was reduced by 25%, upon CNI reduction. If participants were treated with AZA ( alternative to MPA) no dose reduction was needed. Steroid treatment was according to local practice. | ||||||||
All Cause Mortality |
||||||||||||||||
Control: 12 Month Heart | Everolimus + CNI Reduction: 12 Month Heart | Control: 12 Month Lung | Everolimus+CNI Reduction: 12 Month Lung | Control: 24 Month Heart | Everolimus + CNI Reduction: 24 Month Heart | Control: 24 Month Lung | Everolimus + CNI Reduction: 24 Month Lung | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||
Serious Adverse Events |
||||||||||||||||
Control: 12 Month Heart | Everolimus + CNI Reduction: 12 Month Heart | Control: 12 Month Lung | Everolimus+CNI Reduction: 12 Month Lung | Control: 24 Month Heart | Everolimus + CNI Reduction: 24 Month Heart | Control: 24 Month Lung | Everolimus + CNI Reduction: 24 Month Lung | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 23/96 (24%) | 40/94 (42.6%) | 17/46 (37%) | 25/46 (54.3%) | 31/86 (36%) | 25/69 (36.2%) | 21/41 (51.2%) | 16/39 (41%) | ||||||||
Blood and lymphatic system disorders | ||||||||||||||||
Anaemia NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cardiac disorders | ||||||||||||||||
Angina pectoris | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Aortic valve stenosis | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Atrial fibrillation | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Atrial flutter | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Atrial tachycardia | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cardiac failure NOS | 1/96 (1%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Coronary artery atheroma haemorrhage | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Coronary artery disease NOS | 1/96 (1%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Oedema NOS | 0/96 (0%) | 3/94 (3.2%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pulmonary oedema NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Right ventricular failure | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Supraventricular tachycardia | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Endocrine disorders | ||||||||||||||||
Hyperthyroidism | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Gastrointestinal disorders | ||||||||||||||||
Abdominal pain NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Acute abdomen | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Appendicitis | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Diarrhoea NOS | 0/96 (0%) | 2/94 (2.1%) | 1/46 (2.2%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Diverticulitis NOS | 0/96 (0%) | 1/94 (1.1%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Food poisoning NOS | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Gastric ulcer | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Gastric ulcer perforation | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Gastrointestinal haemorrhage NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Ileus | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Inguinal hernia NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Nausea | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pancreatitis NOS | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Peptic ulcer | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Rectal disorder NOS | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Vomiting NOS | 0/96 (0%) | 2/94 (2.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
General disorders | ||||||||||||||||
Chest pain | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Compartment syndrome | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Death NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Fatigue | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Haemorrhage NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Malaise | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Pain NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pyrexia | 1/96 (1%) | 3/94 (3.2%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Hepatobiliary disorders | ||||||||||||||||
Cholelithiasis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Immune system disorders | ||||||||||||||||
Graft rejection | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Heart transplant rejection | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Hypersensitivity NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Infections and infestations | ||||||||||||||||
Brain abscess NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Bronchitis NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Bronchitis acute NOS | 0/96 (0%) | 0/94 (0%) | 2/46 (4.3%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 1/39 (2.6%) | ||||||||
Cholecystitis acute NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cystitis NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cytomegalovirus infection | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Ear infection NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Epididymitis NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Erysipelas | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Gastroenteritis NOS | 2/96 (2.1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 2/86 (2.3%) | 2/69 (2.9%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Herpes simplex | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Herpes zoster | 0/96 (0%) | 2/94 (2.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Infection NOS | 0/96 (0%) | 1/94 (1.1%) | 1/46 (2.2%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Influenza | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 1/41 (2.4%) | 1/39 (2.6%) | ||||||||
Lobar pneumonia NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Localised infection | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Lower respiratory tract infection NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Nasopharyngitis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pneumonia NOS | 3/96 (3.1%) | 7/94 (7.4%) | 3/46 (6.5%) | 6/46 (13%) | 2/86 (2.3%) | 0/69 (0%) | 7/41 (17.1%) | 5/39 (12.8%) | ||||||||
Pneumonia aspergilla | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pseudomonas aeruginosa infection NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 2/46 (4.3%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pyelonephritis NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Sepsis NOS | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Sinusitis NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Upper respiratory tract infection NOS | 0/96 (0%) | 1/94 (1.1%) | 1/46 (2.2%) | 1/46 (2.2%) | 2/86 (2.3%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Urinary tract infection NOS | 1/96 (1%) | 3/94 (3.2%) | 1/46 (2.2%) | 0/46 (0%) | 1/86 (1.2%) | 2/69 (2.9%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Injury, poisoning and procedural complications | ||||||||||||||||
Animal bite | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Forearm fracture | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Fracture NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Hand fracture | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Head injury | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Leg fracture | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Radius fracture | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Investigations | ||||||||||||||||
Arteriogram coronary | 2/96 (2.1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Biopsy lung | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Blood creatinine increased | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Lung function abnormal | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Lung function decreased | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Lymphocyte morphology NOS abnormal | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pericardial drainage | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Weight decreased | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Metabolism and nutrition disorders | ||||||||||||||||
Gout | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Malnutrition NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Musculoskeletal and connective tissue disorders | ||||||||||||||||
Arthritis NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Back pain | 1/96 (1%) | 1/94 (1.1%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Bursitis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Intervertebral disc prolapse | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Localised osteoarthritis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Muscle atrophy | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Myalgia | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Neck pain | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Sciatica | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||
Basal cell carcinoma | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 2/41 (4.9%) | 0/39 (0%) | ||||||||
Benign adrenal neoplasm NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Bowen's disease | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Breast cancer female NOS | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Carcinoma NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Lip neoplasm malignant stage unspecified | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Lung cancer stage unspecified (exc metas | 1/96 (1%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Malignant melanoma stage IV | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Prostate cancer NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Skin carcinoma NOS | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 1/46 (2.2%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Squamous cell carcinoma | 3/96 (3.1%) | 1/94 (1.1%) | 1/46 (2.2%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 2/39 (5.1%) | ||||||||
Squamous cell carcinoma of skin | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Nervous system disorders | ||||||||||||||||
Burning sensation NOS | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cerebrovascular accident NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Dizziness (exc vertigo) | 0/96 (0%) | 2/94 (2.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Epilepsy NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Haemorrhagic stroke | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Migraine NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Monoparesis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Restless leg syndrome | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Syncope | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Syncope aggravated | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Psychiatric disorders | ||||||||||||||||
Confusion | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Renal and urinary disorders | ||||||||||||||||
Fluid retention | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Nephropathy NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Oliguria | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Renal failure NOS | 0/96 (0%) | 2/94 (2.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Renal impairment NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Reproductive system and breast disorders | ||||||||||||||||
Benign prostatic hyperplasia | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Ovarian cyst | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Uterine prolapse | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
Asthma NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Bronchostenosis | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cough | 0/96 (0%) | 1/94 (1.1%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Dyspnoea NOS | 2/96 (2.1%) | 2/94 (2.1%) | 0/46 (0%) | 1/46 (2.2%) | 2/86 (2.3%) | 1/69 (1.4%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Epistaxis | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Excessive bronchial secretion | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 2/41 (4.9%) | 0/39 (0%) | ||||||||
Haemoptysis | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Mediastinal emphysema | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Obliterative bronchiolitis | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 2/46 (4.3%) | 0/86 (0%) | 0/69 (0%) | 6/41 (14.6%) | 1/39 (2.6%) | ||||||||
Pleuritic pain | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pneumothorax NOS | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Pulmonary fibrosis | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Respiratory distress | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Respiratory failure (exc neonatal) | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Skin and subcutaneous tissue disorders | ||||||||||||||||
Angioneurotic oedema | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Dermatitis NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Diabetic foot ulcer | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Surgical and medical procedures | ||||||||||||||||
Angioplasty | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 2/69 (2.9%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cholecystectomy | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Facial lesion excision | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Hip arthroplasty | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Leg amputation | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Operation NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Suture removal | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Vascular disorders | ||||||||||||||||
Arterial stenosis NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Arteriosclerosis | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Cerebral artery thrombosis | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Hypertension aggravated | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Intracranial haemorrhage NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Phlebitis NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Postural hypotension | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Pulmonary embolism | 1/96 (1%) | 1/94 (1.1%) | 2/46 (4.3%) | 2/46 (4.3%) | 1/86 (1.2%) | 2/69 (2.9%) | 1/41 (2.4%) | 1/39 (2.6%) | ||||||||
Pulmonary hypertension NOS | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Subarachnoid haemorrhage NOS | 0/96 (0%) | 0/94 (0%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Transient ischaemic attack | 1/96 (1%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Venous thrombosis NOS | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Venous thrombosis deep limb | 1/96 (1%) | 2/94 (2.1%) | 0/46 (0%) | 0/46 (0%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||
Control: 12 Month Heart | Everolimus + CNI Reduction: 12 Month Heart | Control: 12 Month Lung | Everolimus+CNI Reduction: 12 Month Lung | Control: 24 Month Heart | Everolimus + CNI Reduction: 24 Month Heart | Control: 24 Month Lung | Everolimus + CNI Reduction: 24 Month Lung | |||||||||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 48/96 (50%) | 75/94 (79.8%) | 33/46 (71.7%) | 42/46 (91.3%) | 33/86 (38.4%) | 29/69 (42%) | 21/41 (51.2%) | 27/39 (69.2%) | ||||||||
Blood and lymphatic system disorders | ||||||||||||||||
Leucopenia NOS | 0/96 (0%) | 8/94 (8.5%) | 0/46 (0%) | 8/46 (17.4%) | 1/86 (1.2%) | 1/69 (1.4%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Cardiac disorders | ||||||||||||||||
Oedema NOS | 10/96 (10.4%) | 24/94 (25.5%) | 3/46 (6.5%) | 14/46 (30.4%) | 9/86 (10.5%) | 4/69 (5.8%) | 2/41 (4.9%) | 5/39 (12.8%) | ||||||||
Congenital, familial and genetic disorders | ||||||||||||||||
Epidermal naevus | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Gastrointestinal disorders | ||||||||||||||||
Abdominal pain upper | 1/96 (1%) | 1/94 (1.1%) | 1/46 (2.2%) | 3/46 (6.5%) | 1/86 (1.2%) | 0/69 (0%) | 3/41 (7.3%) | 0/39 (0%) | ||||||||
Diarrhoea NOS | 4/96 (4.2%) | 15/94 (16%) | 3/46 (6.5%) | 7/46 (15.2%) | 0/86 (0%) | 4/69 (5.8%) | 1/41 (2.4%) | 3/39 (7.7%) | ||||||||
Gastritis NOS | 1/96 (1%) | 1/94 (1.1%) | 1/46 (2.2%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Mouth ulceration | 0/96 (0%) | 1/94 (1.1%) | 0/46 (0%) | 5/46 (10.9%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Nausea | 1/96 (1%) | 4/94 (4.3%) | 1/46 (2.2%) | 2/46 (4.3%) | 2/86 (2.3%) | 1/69 (1.4%) | 1/41 (2.4%) | 2/39 (5.1%) | ||||||||
General disorders | ||||||||||||||||
Fall | 2/96 (2.1%) | 0/94 (0%) | 0/46 (0%) | 2/46 (4.3%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Fatigue | 5/96 (5.2%) | 6/94 (6.4%) | 2/46 (4.3%) | 2/46 (4.3%) | 0/86 (0%) | 0/69 (0%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Pyrexia | 6/96 (6.3%) | 1/94 (1.1%) | 2/46 (4.3%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 1/41 (2.4%) | 0/39 (0%) | ||||||||
Infections and infestations | ||||||||||||||||
Bronchitis NOS | 0/96 (0%) | 5/94 (5.3%) | 3/46 (6.5%) | 2/46 (4.3%) | 0/86 (0%) | 0/69 (0%) | 2/41 (4.9%) | 2/39 (5.1%) | ||||||||
Infection NOS | 0/96 (0%) | 3/94 (3.2%) | 1/46 (2.2%) | 0/46 (0%) | 3/86 (3.5%) | 2/69 (2.9%) | 2/41 (4.9%) | 2/39 (5.1%) | ||||||||
Influenza | 5/96 (5.2%) | 2/94 (2.1%) | 2/46 (4.3%) | 1/46 (2.2%) | 1/86 (1.2%) | 2/69 (2.9%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Nasopharyngitis | 15/96 (15.6%) | 18/94 (19.1%) | 12/46 (26.1%) | 11/46 (23.9%) | 12/86 (14%) | 7/69 (10.1%) | 7/41 (17.1%) | 8/39 (20.5%) | ||||||||
Pneumonia NOS | 5/96 (5.2%) | 3/94 (3.2%) | 2/46 (4.3%) | 5/46 (10.9%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 3/39 (7.7%) | ||||||||
Upper respiratory tract infection NOS | 1/96 (1%) | 2/94 (2.1%) | 6/46 (13%) | 9/46 (19.6%) | 2/86 (2.3%) | 2/69 (2.9%) | 4/41 (9.8%) | 6/39 (15.4%) | ||||||||
Urinary tract infection NOS | 0/96 (0%) | 3/94 (3.2%) | 3/46 (6.5%) | 4/46 (8.7%) | 1/86 (1.2%) | 1/69 (1.4%) | 2/41 (4.9%) | 3/39 (7.7%) | ||||||||
Investigations | ||||||||||||||||
Blood creatinine increased | 2/96 (2.1%) | 1/94 (1.1%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Metabolism and nutrition disorders | ||||||||||||||||
Hypercholesterolaemia | 4/96 (4.2%) | 0/94 (0%) | 3/46 (6.5%) | 6/46 (13%) | 1/86 (1.2%) | 2/69 (2.9%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Hypokalaemia | 0/96 (0%) | 1/94 (1.1%) | 1/46 (2.2%) | 4/46 (8.7%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Musculoskeletal and connective tissue disorders | ||||||||||||||||
Arthralgia | 5/96 (5.2%) | 6/94 (6.4%) | 2/46 (4.3%) | 3/46 (6.5%) | 0/86 (0%) | 1/69 (1.4%) | 1/41 (2.4%) | 1/39 (2.6%) | ||||||||
Arthritis NOS | 1/96 (1%) | 0/94 (0%) | 0/46 (0%) | 3/46 (6.5%) | 0/86 (0%) | 1/69 (1.4%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Myalgia | 3/96 (3.1%) | 7/94 (7.4%) | 1/46 (2.2%) | 1/46 (2.2%) | 2/86 (2.3%) | 0/69 (0%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Pain in limb | 1/96 (1%) | 5/94 (5.3%) | 0/46 (0%) | 1/46 (2.2%) | 2/86 (2.3%) | 1/69 (1.4%) | 0/41 (0%) | 0/39 (0%) | ||||||||
Nervous system disorders | ||||||||||||||||
Headache NOS | 7/96 (7.3%) | 7/94 (7.4%) | 3/46 (6.5%) | 5/46 (10.9%) | 1/86 (1.2%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Respiratory, thoracic and mediastinal disorders | ||||||||||||||||
Cough | 3/96 (3.1%) | 5/94 (5.3%) | 3/46 (6.5%) | 3/46 (6.5%) | 0/86 (0%) | 3/69 (4.3%) | 1/41 (2.4%) | 1/39 (2.6%) | ||||||||
Excessive bronchial secretion | 0/96 (0%) | 0/94 (0%) | 0/46 (0%) | 0/46 (0%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 2/39 (5.1%) | ||||||||
Skin and subcutaneous tissue disorders | ||||||||||||||||
Acne NOS | 0/96 (0%) | 11/94 (11.7%) | 0/46 (0%) | 1/46 (2.2%) | 0/86 (0%) | 0/69 (0%) | 0/41 (0%) | 1/39 (2.6%) | ||||||||
Vascular disorders | ||||||||||||||||
Hypertension NOS | 5/96 (5.2%) | 4/94 (4.3%) | 4/46 (8.7%) | 6/46 (13%) | 0/86 (0%) | 3/69 (4.3%) | 2/41 (4.9%) | 3/39 (7.7%) | ||||||||
Hypertension aggravated | 0/96 (0%) | 5/94 (5.3%) | 1/46 (2.2%) | 1/46 (2.2%) | 3/86 (3.5%) | 1/69 (1.4%) | 1/41 (2.4%) | 1/39 (2.6%) |
Limitations/Caveats
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 (ie, data from all sites) in the clinical trial.
Results Point of Contact
Name/Title | Study Director |
---|---|
Organization | Novartis Pharmaceuticals |
Phone | 862 778-8300 |
- CRAD001AIC01