Trial Outcomes & Findings for Everolimus in de Novo Kidney Transplant Recipients (NCT NCT01410448)
NCT ID: NCT01410448
Last Updated: 2017-06-16
Results Overview
The percentage of participants without wound healing complications was assessed. Wound healing complications consisted of lymphorrhea, fluid collections, wound dehiscence, wound infections and incisional hernia. In the worst-case scenario, failure, i.e. at least one healing complication occurrence, was identified in one of the following cases: wound complication occurrence, missing information about wound complication occurrence, or study discontinuation due to any reason.
COMPLETED
PHASE3
383 participants
3 months
2017-06-16
Participant Flow
This study included a 3 month treatment period followed by an observational follow-up period. Participants were treated as per local practice during follow-up and a follow-up evaluation was performed at 12 months.
Participants were randomized in a 1:1 ratio to one of the 2 treatment groups.
Participant milestones
| Measure |
Immediate Everolimus (IE)
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Overall Study
STARTED
|
193
|
190
|
|
Overall Study
Intent-to Treat (ITT) Analysis Set
|
193
|
190
|
|
Overall Study
Modified ITT Analysis Set
|
161
|
149
|
|
Overall Study
COMPLETED
|
181
|
155
|
|
Overall Study
NOT COMPLETED
|
12
|
35
|
Reasons for withdrawal
| Measure |
Immediate Everolimus (IE)
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Overall Study
No conversion to everolimus
|
0
|
24
|
|
Overall Study
Graft loss
|
4
|
1
|
|
Overall Study
Administrative issues
|
2
|
1
|
|
Overall Study
Lost to Follow-up
|
1
|
0
|
|
Overall Study
Withdrawal by Subject
|
3
|
2
|
|
Overall Study
Protocol Violation
|
0
|
4
|
|
Overall Study
Death
|
2
|
3
|
Baseline Characteristics
Everolimus in de Novo Kidney Transplant Recipients
Baseline characteristics by cohort
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
Total
n=383 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
51.46 Years
STANDARD_DEVIATION 11.37 • n=5 Participants
|
51.19 Years
STANDARD_DEVIATION 12.29 • n=7 Participants
|
51.32 Years
STANDARD_DEVIATION 11.82 • n=5 Participants
|
|
Sex: Female, Male
Female
|
59 Participants
n=5 Participants
|
58 Participants
n=7 Participants
|
117 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
134 Participants
n=5 Participants
|
132 Participants
n=7 Participants
|
266 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsPopulation: The safety population, which included all randomized participants who were treated and had at least one safety assessment, was analyzed.
The percentage of participants without wound healing complications was assessed. Wound healing complications consisted of lymphorrhea, fluid collections, wound dehiscence, wound infections and incisional hernia. In the worst-case scenario, failure, i.e. at least one healing complication occurrence, was identified in one of the following cases: wound complication occurrence, missing information about wound complication occurrence, or study discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario
|
68.39 Percentage of participants
|
61.58 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: The safety population, which included all randomized participants who were treated and had at least one safety assessment, was analyzed.
The percentage of participants without wound healing complications was assessed. Wound healing complications consisted of lymphorrhea, fluid collections, wound dehiscence, wound infections and incisional hernia. In the worst-case scenario, failure, i.e. at least one healing complication occurrence, was identified in one of the following cases: wound complication occurrence, missing information about wound complication occurrence or study discontinuation due to any reason for participants who did not complete the 12 month follow-up visit.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants Without Wound Healing Complications - Worst-case Scenario
|
65.80 Percentage of participants
|
59.47 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
The percentage of participants who experienced treatment failure was assessed. Treatment failure was defined as the occurrence of at least one failure event among death, graft loss or biopsy-proven acute rejection (BPAR). In the worst-case scenario, treatment failure was identified in one of the following cases: occurrence of at least one treatment failure event or study discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants Who Experienced Treatment Failure - Worst-case Scenario
|
11.40 Percentage of participants
|
21.05 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 Months, 12 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
The percentage of deaths was assessed. In the worst-case scenario, failure, i.e. death, was identified in one of the following cases: participant's death or study discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Patient Survival Rate: Percentage of Deaths - Worst-case Scenario
|
6.22 Percentage of participants
|
18.42 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
The percentage of participants who experienced death or graft loss was assessed. In the worst-case scenario, failure, i.e. participants death or graft loss, was identified in one of the following cases: occurrence of at least one failure event or study discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Participant/Graft Survival Rate: Percentage of Participants With Failure Events of Death or Graft Loss - Worst-case Scenario
|
6.74 Percentage of participants
|
18.42 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 months, 12 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
The percentage of participants who experienced graft loss was assessed. In the worst-case scenario, failure, i.e. graft loss, was identified in one of the following cases: occurrence of graft loss or discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Graft Survival Rate: Percentage of Participants With Graft Loss - Worst-case Scenario
3 months
|
6.74 Percentage of participants
|
18.42 Percentage of participants
|
|
Graft Survival Rate: Percentage of Participants With Graft Loss - Worst-case Scenario
12 months
|
7.25 Percentage of participants
|
19.47 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 Months, 12 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
A biopsy-proven acute rejection was defined as a biopsy graded IA, IB, IIA, IIB or III. In the worst-case scenario, failure, i.e. BPAR, was identified in one of the following cases: occurrence of BPAR or study discontinuation due to any reason.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With BPAR - Worst-case Scenario
3 monts
|
11.40 Percentage of participants
|
21.05 Percentage of participants
|
|
Percentage of Participants With BPAR - Worst-case Scenario
12 months
|
15.54 Percentage of participants
|
24.74 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 MonthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
DGF was defined as the need for dialysis in the first week after transplant, excluding Renal Replacement Therapy within the first 24 hours after transplantation.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With Delayed Graft Function (DGF) -
|
23.83 Percentage of participants
|
31.58 Percentage of participants
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: Participants from the Intent-to-Treat (ITT) populations who required dialysis, 46 (23.83%) of the IE group and 60 (31.58%) of the DE group, were analyzed. The ITT population included all randomized participants who were treated.
The duration of DGF was defined as the elapsed time from first to last day of post-transplant dialysis.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=46 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=60 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Duration of DGF
|
8.50 Days
Interval 1.0 to 93.0
|
5.50 Days
Interval 1.0 to 76.0
|
SECONDARY outcome
Timeframe: baseline, 3 MonthsPopulation: Participants from the ITT, who had both baseline and month 3 measurements, were included in the analysis for the month 3 time point. The ITT population included all randomized participants who were treated.
Renal function was assessed by measuring serum creatinine and serum urea and by calculating creatinine clearance using the MDRD-4 formula. eGFR = 186.3\*(serum creatinine \[mg/dL\])\^-1.154 \* (age at screening) -0.203 \* (0.742 if female) \* (1.21 if African American). A positive change from baseline indicates improvement.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=187 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=183 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - ITT
|
38.64 mL/min
Standard Deviation 22.45
|
39.13 mL/min
Standard Deviation 21.46
|
SECONDARY outcome
Timeframe: baseline, 12 monthsPopulation: Participants from the modified ITT, who had both baseline and month 12 measurements, were included in the analysis for the month 12 time point. The modified ITT included participants who completed the Core Phase (at 3 months) without discontinuing the treatment and performed the subsequent follow-up evaluation at 12 months after transplant.
Renal function was assessed by measuring serum creatinine and serum urea and by calculating creatinine clearance using the MDRD-4 formula. eGFR = 186.3\*(serum creatinine \[mg/dL\])\^-1.154 \* (age at screening) -0.203 \* (0.742 if female) \* (1.21 if African American). A positive change from baseline indicates improvement.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=151 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=142 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) (Calculated With Modified Diet in Renal Disease (MDRD)-4 Formula - Modified ITT
|
41.26 mL/min
Standard Deviation 18.69
|
41.56 mL/min
Standard Deviation 19.90
|
SECONDARY outcome
Timeframe: baseline, 3 monthsPopulation: Participants from the ITT, who had both baseline and the post-baseline measurement for a given post-baseline time point, were included in the analysis for that post-baseline time point. The ITT population included all randomized participants who were treated.
Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=187 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=183 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Change From Baseline in Serum Creatinine - ITT
|
-4.79 mg/dL
Standard Deviation 2.74
|
-5.13 mg/dL
Standard Deviation 2.32
|
SECONDARY outcome
Timeframe: baseline, 12 monthsPopulation: Participants from the modified ITT, who had both baseline and month 12 measurements, were included in the analysis for the month 12 time point. The modified ITT included participants who completed the Core Phase (at 3 months) without discontinuing the treatment and performed the subsequent follow-up evaluation at 12 months after transplant.
Blood samples were collected to assess serum creatinine measurements. A negative change from baseline indicates improvement.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=150 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=141 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Change From Baseline in Serum Creatinine - Modified ITT
|
-4.96 mg/dL
Standard Deviation 2.48
|
-5.22 mg/dL
Standard Deviation 2.24
|
SECONDARY outcome
Timeframe: 3 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
Incidence of proteinuria (\>1,000 mg/day in urine collected in 24 hours or \> 1.0 if measured on the urine protein/creatinine concentration ratio in a spot urine sample) was assessed.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With Proteinuria
No
|
68.91 Percentage of participants
|
68.42 Percentage of participants
|
|
Percentage of Participants With Proteinuria
Yes
|
4.15 Percentage of participants
|
4.21 Percentage of participants
|
|
Percentage of Participants With Proteinuria
Missing
|
26.94 Percentage of participants
|
27.37 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: The intent to treat (ITT) population, which included all randomized participants who were treated, was analyzed.
AR was defined as an episode of increased serum creatinine \>30% that was clinically diagnosed as an acute rejection but was not biopsy proven.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=193 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With Acute Rejection (AR)
|
12.44 Percentage of participants
|
10.53 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Participants from the modified ITT, who had values at 12 months, were analyzed. The modified ITT included participants who completed the Core Phase (at 3 months) without discontinuing the treatment and performed the subsequent follow-up evaluation at 12 months after transplant.
The percentage of participants with a new onset of malignancy was assessed.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=159 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=147 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With a New Onset of Malignancy
|
0 Percentage of participants
|
0.68 Percentage of participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: Participants from the modified ITT, who had values at 12 months, were analyzed. The modified ITT included participants who completed the Core Phase (at 3 months) without discontinuing the treatment and performed the subsequent follow-up evaluation at 12 months after transplant.
The percentage of participants with a new onset of diabetes was assessed.
Outcome measures
| Measure |
Immediate Everolimus (IE)
n=159 Participants
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=148 Participants
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Percentage of Participants With a New Onset of Diabetes
|
3.14 Percentage of participants
|
4.05 Percentage of participants
|
Adverse Events
Immediate Everolimus (IE)
Delayed Everolimus (DE)
Serious adverse events
| Measure |
Immediate Everolimus (IE)
n=193 participants at risk
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 participants at risk
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
1.6%
3/193
|
1.1%
2/190
|
|
Blood and lymphatic system disorders
Haemolytic anaemia
|
0.00%
0/193
|
0.53%
1/190
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.0%
2/193
|
1.6%
3/190
|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
1.6%
3/193
|
0.00%
0/190
|
|
Cardiac disorders
Acute myocardial infarction
|
1.0%
2/193
|
0.53%
1/190
|
|
Cardiac disorders
Cardiac arrest
|
0.52%
1/193
|
0.00%
0/190
|
|
Cardiac disorders
Cardiomyopathy
|
0.00%
0/193
|
0.53%
1/190
|
|
Cardiac disorders
Myocardial infarction
|
0.52%
1/193
|
0.53%
1/190
|
|
Cardiac disorders
Myocardial ischaemia
|
0.00%
0/193
|
0.53%
1/190
|
|
Congenital, familial and genetic disorders
Protein S deficiency
|
0.52%
1/193
|
0.00%
0/190
|
|
Gastrointestinal disorders
Abdominal pain
|
0.52%
1/193
|
0.53%
1/190
|
|
Gastrointestinal disorders
Ascites
|
0.00%
0/193
|
0.53%
1/190
|
|
Gastrointestinal disorders
Intestinal obstruction
|
0.00%
0/193
|
0.53%
1/190
|
|
Gastrointestinal disorders
Intra-abdominal haemorrhage
|
1.0%
2/193
|
0.00%
0/190
|
|
Gastrointestinal disorders
Localised intraabdominal fluid collection
|
0.52%
1/193
|
0.00%
0/190
|
|
Gastrointestinal disorders
Pancreatitis
|
0.00%
0/193
|
0.53%
1/190
|
|
Gastrointestinal disorders
Retroperitoneal haemorrhage
|
1.0%
2/193
|
0.00%
0/190
|
|
General disorders
Hyperpyrexia
|
0.52%
1/193
|
0.53%
1/190
|
|
General disorders
Impaired healing
|
0.52%
1/193
|
0.00%
0/190
|
|
General disorders
Multi-organ failure
|
0.00%
0/193
|
0.53%
1/190
|
|
General disorders
Oedema
|
0.00%
0/193
|
0.53%
1/190
|
|
General disorders
Oedema peripheral
|
0.52%
1/193
|
0.00%
0/190
|
|
General disorders
Pyrexia
|
1.6%
3/193
|
0.53%
1/190
|
|
Hepatobiliary disorders
Cholecystitis
|
0.52%
1/193
|
0.00%
0/190
|
|
Hepatobiliary disorders
Cholecystitis acute
|
0.00%
0/193
|
0.53%
1/190
|
|
Hepatobiliary disorders
Hydrocholecystis
|
0.00%
0/193
|
0.53%
1/190
|
|
Hepatobiliary disorders
Liver disorder
|
0.52%
1/193
|
0.00%
0/190
|
|
Immune system disorders
Autoimmune disorder
|
0.00%
0/193
|
0.53%
1/190
|
|
Immune system disorders
Kidney transplant rejection
|
5.7%
11/193
|
2.1%
4/190
|
|
Immune system disorders
Transplant rejection
|
1.6%
3/193
|
0.53%
1/190
|
|
Infections and infestations
Abscess
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Bronchopneumonia
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Cystitis
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/193
|
1.6%
3/190
|
|
Infections and infestations
Device related infection
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Encephalitis
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Enterobacter infection
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Escherichia infection
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Infected lymphocele
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Klebsiella infection
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Lung infection
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Peritonitis
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Pneumonia
|
0.52%
1/193
|
0.53%
1/190
|
|
Infections and infestations
Pyelonephritis
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Renal abscess
|
0.52%
1/193
|
0.00%
0/190
|
|
Infections and infestations
Retroperitoneal abscess
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Sepsis
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Septic shock
|
0.00%
0/193
|
0.53%
1/190
|
|
Infections and infestations
Urinary tract infection
|
4.1%
8/193
|
3.7%
7/190
|
|
Infections and infestations
Urosepsis
|
0.52%
1/193
|
1.1%
2/190
|
|
Infections and infestations
Wound infection
|
1.6%
3/193
|
1.1%
2/190
|
|
Injury, poisoning and procedural complications
Complications of transplanted kidney
|
1.0%
2/193
|
1.6%
3/190
|
|
Injury, poisoning and procedural complications
Expired product administered
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Femur fracture
|
0.52%
1/193
|
0.53%
1/190
|
|
Injury, poisoning and procedural complications
Graft loss
|
1.6%
3/193
|
0.53%
1/190
|
|
Injury, poisoning and procedural complications
Graft thrombosis
|
0.00%
0/193
|
1.1%
2/190
|
|
Injury, poisoning and procedural complications
Incisional hernia
|
0.00%
0/193
|
0.53%
1/190
|
|
Injury, poisoning and procedural complications
Perinephric collection
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Perirenal haematoma
|
1.0%
2/193
|
0.53%
1/190
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Renal haematoma
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Renal transplant failure
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Subcutaneous haematoma
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Ureteric anastomosis complication
|
0.52%
1/193
|
0.00%
0/190
|
|
Injury, poisoning and procedural complications
Wound dehiscence
|
1.0%
2/193
|
1.1%
2/190
|
|
Investigations
Blood creatinine increased
|
2.1%
4/193
|
2.6%
5/190
|
|
Investigations
Platelet count decreased
|
0.52%
1/193
|
0.53%
1/190
|
|
Metabolism and nutrition disorders
Dehydration
|
0.52%
1/193
|
0.53%
1/190
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
0.00%
0/193
|
0.53%
1/190
|
|
Metabolism and nutrition disorders
Fluid overload
|
1.0%
2/193
|
0.00%
0/190
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
0.52%
1/193
|
0.00%
0/190
|
|
Metabolism and nutrition disorders
Metabolic disorder
|
0.00%
0/193
|
1.1%
2/190
|
|
Musculoskeletal and connective tissue disorders
Arthralgia
|
0.52%
1/193
|
0.00%
0/190
|
|
Musculoskeletal and connective tissue disorders
Pelvic deformity
|
0.52%
1/193
|
0.00%
0/190
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Renal cancer
|
0.00%
0/193
|
0.53%
1/190
|
|
Nervous system disorders
Ataxia
|
0.52%
1/193
|
0.00%
0/190
|
|
Nervous system disorders
Cerebral haemorrhage
|
0.00%
0/193
|
0.53%
1/190
|
|
Nervous system disorders
Coma
|
0.52%
1/193
|
0.00%
0/190
|
|
Nervous system disorders
Ischaemic stroke
|
0.52%
1/193
|
0.00%
0/190
|
|
Nervous system disorders
Tremor
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Dysuria
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Hydronephrosis
|
0.52%
1/193
|
0.53%
1/190
|
|
Renal and urinary disorders
Oliguria
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Perinephric effusion
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Proteinuria
|
0.00%
0/193
|
1.1%
2/190
|
|
Renal and urinary disorders
Renal artery stenosis
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Renal artery thrombosis
|
0.00%
0/193
|
0.53%
1/190
|
|
Renal and urinary disorders
Renal failure
|
0.52%
1/193
|
0.53%
1/190
|
|
Renal and urinary disorders
Renal failure acute
|
0.00%
0/193
|
1.1%
2/190
|
|
Renal and urinary disorders
Renal impairment
|
1.6%
3/193
|
1.1%
2/190
|
|
Renal and urinary disorders
Renal ischaemia
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Renal tubular necrosis
|
0.52%
1/193
|
0.53%
1/190
|
|
Renal and urinary disorders
Renal vein thrombosis
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Tubulointerstitial nephritis
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Urinary fistula
|
0.52%
1/193
|
0.53%
1/190
|
|
Renal and urinary disorders
Urinary retention
|
0.52%
1/193
|
0.00%
0/190
|
|
Renal and urinary disorders
Urinoma
|
0.52%
1/193
|
1.1%
2/190
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.52%
1/193
|
0.00%
0/190
|
|
Respiratory, thoracic and mediastinal disorders
Pneumonitis
|
0.00%
0/193
|
0.53%
1/190
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary embolism
|
0.00%
0/193
|
0.53%
1/190
|
|
Surgical and medical procedures
Bladder catheter replacement
|
0.52%
1/193
|
0.00%
0/190
|
|
Surgical and medical procedures
Lymphocele marsupialisation
|
0.52%
1/193
|
0.53%
1/190
|
|
Vascular disorders
Arterial thrombosis
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Circulatory collapse
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Haematoma
|
1.6%
3/193
|
0.53%
1/190
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Hypotension
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Lymphocele
|
3.6%
7/193
|
3.7%
7/190
|
|
Vascular disorders
Lymphorrhoea
|
0.00%
0/193
|
1.1%
2/190
|
|
Vascular disorders
Shock
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Shock haemorrhagic
|
0.52%
1/193
|
0.00%
0/190
|
|
Vascular disorders
Thrombophlebitis
|
0.00%
0/193
|
0.53%
1/190
|
|
Vascular disorders
Thrombosis
|
0.52%
1/193
|
0.00%
0/190
|
|
Vascular disorders
Venous thrombosis
|
0.52%
1/193
|
0.00%
0/190
|
Other adverse events
| Measure |
Immediate Everolimus (IE)
n=193 participants at risk
Everolimus was started within 48 hours after graft reperfusion at a starting dose of 0.75 mg twice daily in combination with low-dose cyclosporine and steroids for 3 months.
|
Delayed Everolimus (DE)
n=190 participants at risk
The standard dose of mycophenolate sodium was administered within 48 hours after graft reperfusion in combination with a full dose of cyclosporine and steroids. After28 +/- 4 days of treatment, mycophenolate sodium was discontinued and everolimus was introduced at a starting dose of 0.75 mg twice daily for 3 months.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
34.7%
67/193
|
30.5%
58/190
|
|
Blood and lymphatic system disorders
Leukopenia
|
4.1%
8/193
|
7.4%
14/190
|
|
Gastrointestinal disorders
Abdominal pain
|
7.3%
14/193
|
7.9%
15/190
|
|
Gastrointestinal disorders
Constipation
|
6.2%
12/193
|
6.8%
13/190
|
|
Gastrointestinal disorders
Nausea
|
2.1%
4/193
|
7.4%
14/190
|
|
General disorders
Oedema peripheral
|
8.8%
17/193
|
7.4%
14/190
|
|
General disorders
Pyrexia
|
8.3%
16/193
|
7.4%
14/190
|
|
Infections and infestations
Cytomegalovirus infection
|
6.7%
13/193
|
8.4%
16/190
|
|
Infections and infestations
Urinary tract infection
|
17.6%
34/193
|
17.9%
34/190
|
|
Injury, poisoning and procedural complications
Complications of transplanted kidney
|
13.5%
26/193
|
12.1%
23/190
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
14.5%
28/193
|
12.6%
24/190
|
|
Metabolism and nutrition disorders
Hypercholesterolaemia
|
10.4%
20/193
|
4.7%
9/190
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
5.2%
10/193
|
9.5%
18/190
|
|
Metabolism and nutrition disorders
Hyperlipidaemia
|
3.1%
6/193
|
5.3%
10/190
|
|
Metabolism and nutrition disorders
Hyperphosphataemia
|
10.4%
20/193
|
6.8%
13/190
|
|
Metabolism and nutrition disorders
Hypertriglyceridaemia
|
7.3%
14/193
|
4.7%
9/190
|
|
Metabolism and nutrition disorders
Hyperuricaemia
|
10.9%
21/193
|
13.2%
25/190
|
|
Metabolism and nutrition disorders
Hypocalcaemia
|
12.4%
24/193
|
15.8%
30/190
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
13.5%
26/193
|
12.6%
24/190
|
|
Renal and urinary disorders
Haematuria
|
7.3%
14/193
|
1.6%
3/190
|
|
Vascular disorders
Haematoma
|
6.2%
12/193
|
3.2%
6/190
|
|
Vascular disorders
Hypertension
|
17.6%
34/193
|
15.8%
30/190
|
|
Vascular disorders
Lymphocele
|
13.0%
25/193
|
17.4%
33/190
|
|
Vascular disorders
Lymphorrhoea
|
3.1%
6/193
|
5.8%
11/190
|
Additional Information
Study Director
Novartis Pharmaceuticals
Results disclosure agreements
- Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (i.e., data from all sites) in the clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER