Trial Outcomes & Findings for Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients (NCT NCT01079143)
NCT ID: NCT01079143
Last Updated: 2014-03-18
Results Overview
Progression of Interstitial Fibrosis/Tabular Atrophy (IF/TA) is the percentage (%) of participants with an increase \>= 1 in IF/TA grade according to Banff (2005 - 2007)according to Epithelial-mesenchymal transition (EMT) profile and by treatment groups. Grade I (the better): mild interstitial fibrosis and tubular atrophy (\<25% of cortical area) Grade II : moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area) Grade III (the worse) : severe interstitial fibrosis and tubular atrophy (\>50% of cortical area)
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
194 participants
Primary outcome timeframe
Month 3 (M3) and Month 12 (M12) post transplantation
Results posted on
2014-03-18
Participant Flow
EMT+: ≥ 10% tubular cells showing de novo expression of vimentin (or translocation of β catenin if inconclusive) into the cytoplasm EMT-: \< 10% tubular cells showing de novo expression of vimentin (or translocation of β catenin if inconclusive) into the cytoplasm
Participant milestones
| Measure |
Certican EMT+
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Certican EMT-
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Overall Study
STARTED
|
36
|
60
|
39
|
59
|
|
Overall Study
Exposed
|
36
|
60
|
39
|
59
|
|
Overall Study
Month 3 (M3) Biopsies
|
36
|
59
|
39
|
59
|
|
Overall Study
Month 12 (M12) Biopsies
|
26
|
43
|
32
|
53
|
|
Overall Study
M3 and M12 Biopsies
|
26
|
43
|
32
|
53
|
|
Overall Study
COMPLETED
|
27
|
43
|
34
|
54
|
|
Overall Study
NOT COMPLETED
|
9
|
17
|
5
|
5
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Progression of Renal Interstitial Fibrosis / Tubular Atrophy (IF/TA) According to Epithelial-mesenchymal Transition (EMT) and Immunosuppressive Regimen (Everolimus Based Versus CNI Based) in de Novo Renal Transplant Recipients
Baseline characteristics by cohort
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Certican EMT-
n=60 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Total
n=194 Participants
Total of all reporting groups
|
|---|---|---|---|---|---|
|
Age, Continuous
|
51.2 years
STANDARD_DEVIATION 10.7 • n=5 Participants
|
46.4 years
STANDARD_DEVIATION 12.9 • n=7 Participants
|
50.0 years
STANDARD_DEVIATION 10.0 • n=5 Participants
|
50.7 years
STANDARD_DEVIATION 11.7 • n=4 Participants
|
49.3 years
STANDARD_DEVIATION 11.7 • n=21 Participants
|
|
Sex: Female, Male
Female
|
17 Participants
n=5 Participants
|
17 Participants
n=7 Participants
|
16 Participants
n=5 Participants
|
16 Participants
n=4 Participants
|
66 Participants
n=21 Participants
|
|
Sex: Female, Male
Male
|
19 Participants
n=5 Participants
|
43 Participants
n=7 Participants
|
23 Participants
n=5 Participants
|
43 Participants
n=4 Participants
|
128 Participants
n=21 Participants
|
|
BMI
|
24.3 kg/m^2
STANDARD_DEVIATION 4.6 • n=5 Participants
|
26.0 kg/m^2
STANDARD_DEVIATION 4.6 • n=7 Participants
|
25.6 kg/m^2
STANDARD_DEVIATION 4.0 • n=5 Participants
|
25.3 kg/m^2
STANDARD_DEVIATION 4.2 • n=4 Participants
|
25.4 kg/m^2
STANDARD_DEVIATION 4.4 • n=21 Participants
|
PRIMARY outcome
Timeframe: Month 3 (M3) and Month 12 (M12) post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12. The primary comparison concerned only the Certican and the Neoral EMT+ groups.
Progression of Interstitial Fibrosis/Tabular Atrophy (IF/TA) is the percentage (%) of participants with an increase \>= 1 in IF/TA grade according to Banff (2005 - 2007)according to Epithelial-mesenchymal transition (EMT) profile and by treatment groups. Grade I (the better): mild interstitial fibrosis and tubular atrophy (\<25% of cortical area) Grade II : moderate interstitial fibrosis and tubular atrophy (26-50% of cortical area) Grade III (the worse) : severe interstitial fibrosis and tubular atrophy (\>50% of cortical area)
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Number of Participants With Progression of Renal Graft Fibrosis (Primary Comparison - ITT Population
Participants with an IF/TA grade <= II at M3
|
26 Participants
|
31 Participants
|
—
|
—
|
|
Number of Participants With Progression of Renal Graft Fibrosis (Primary Comparison - ITT Population
Participants with Fibrosis progression, M3 to M12
|
12 Participants
|
16 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Incidence and severity of IF/TA according to 2005/2007 Banff classification system grades (grades l to lll). IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (\<25%), grade II (25-50%) and grade III (\>50% of lesions).
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
Interstitial Fibrosis/Tubular Atrophy (IF/TA)
|
13 Number of participants
|
38 Number of participants
|
13 Number of participants
|
44 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IF/TA grade at M3 at grade 1
|
11 Number of participants
|
5 Number of participants
|
17 Number of participants
|
9 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IFTA grade at M3 at grade II
|
2 Number of participants
|
0 Number of participants
|
1 Number of participants
|
0 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IF/TA grade at M3 at grade III
|
0 Number of participants
|
0 Number of participants
|
1 Number of participants
|
0 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IF/TA grade at M12 at grade 0
|
9 Number of participants
|
20 Number of participants
|
7 Number of participants
|
31 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IT/TA grade at M12 at grade I
|
8 Number of participants
|
18 Number of participants
|
15 Number of participants
|
15 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IF/TA grade at M12 at grade II
|
6 Number of participants
|
5 Number of participants
|
9 Number of participants
|
6 Number of participants
|
|
Interstitial Fibrosis/Tabular Atrophy (IF/TA)
IF/TA grade at M12 at grade III
|
3 Number of participants
|
0 Number of participants
|
1 Number of participants
|
1 Number of participants
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Difference (M12 - M3) in IF/TA grade. IF/TA grade was assessed during centralized reading according to the Banff 2005/2007 classification comprising grade I (\<25%), grade II (25-50%) and grade III (\>50% of lesions).
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade
Difference in IF/TA grade -1
|
5 Number of Participants
|
1 Number of Participants
|
7 Number of Participants
|
2 Number of Participants
|
|
Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade
Difference in IF/TA grade 0
|
9 Number of Participants
|
21 Number of Participants
|
9 Number of Participants
|
33 Number of Participants
|
|
Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade
Difference in IF/TA grade 1
|
7 Number of Participants
|
18 Number of Participants
|
11 Number of Participants
|
13 Number of Participants
|
|
Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade
Difference in IF/TA grade 2
|
3 Number of Participants
|
3 Number of Participants
|
5 Number of Participants
|
5 Number of Participants
|
|
Change in Interstitial Fibrosis/Tabular Atrophy (IF/TA) Grade
Difference in IF/TA grade 3
|
2 Number of Participants
|
NA Number of Participants
No analysis done for grade lll for the Certican EMT- arm
|
0 Number of Participants
|
NA Number of Participants
No analysis done for grade lll for the Neoral EMT- arm
|
SECONDARY outcome
Timeframe: M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Composite factors regarding fibrosis progression at 12 months using a logistic regression model; the parameters initially considered concerned the demographic characteristics of both recipient and donor, transplantation characteristics, hypertension, diabetes, study treatments, immunosuppression, EMT, IF/TA, function at M3, the onset of acute rejection, the presence of anti-donor antibodies at M12, infections and BK virus viremia. Arteriolar hyaline thickening is thickening of the walls of arterioles by the deposition of homogeneous pink hyaline material. BPAR is biopsy proven acute rejection. TEM progression is the increase ≥ 1 of TEM score between Month 3 and Month 12
Outcome measures
| Measure |
Certican EMT+
n=67 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=86 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Risk Factors of IF/TA Progression
Donor Sex - Male
|
45 Participants
|
48 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Donor Sex - Female
|
22 Participants
|
38 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Donor Age - <=50 years
|
28 Participants
|
48 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Donor Age - >50 years
|
39 Participants
|
38 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Expanded Criteria donor: NO
|
40 Participants
|
63 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Expanded Criteria Donor: Yes
|
27 Participants
|
23 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Delayed graft function: No
|
52 Participants
|
76 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Delayed graft function: Yes
|
15 Participants
|
10 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
CC at M3 <50 mL/min/1.73m^2
|
40 Participants
|
35 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
CC at M3 >=50 mL/min/1.73m^2 (n=67, 85)
|
27 Participants
|
50 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Mesangial matrix increase at M3 - 0 (n=64, 85)
|
59 Participants
|
84 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Mesangial matrix (mm) increase at M3: 1 (n=64, 85)
|
2 Participants
|
1 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Mesangial matrix increase at M3: 2 (n=64, 85)
|
3 Participants
|
0 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Interstitial fibrosis (ci) at M3: 0 (n=66, 85)
|
52 Participants
|
55 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Interstitial fibrosis (ci) at M3: 1 (n=66, 85)
|
14 Participants
|
27 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Interstitial fibrosis (ci) at M3: 2 (n=66, 85)
|
0 Participants
|
3 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Arteriolar hyaline thickening (ah) at M3: 0
|
36 Participants
|
56 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Arteriolar hyaline thickening (ah) at M3: 1
|
15 Participants
|
21 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Arteriolar hyaline thickening (ah) at M3: 2
|
10 Participants
|
8 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
Arteriolar hyaline thickening (ah) at M3: 3
|
6 Participants
|
1 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
BPAR - No
|
55 Participants
|
79 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
BPAR - Yes
|
12 Participants
|
7 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
TEM Progression fron M3-M12: No (n=67, 83)
|
26 Participants
|
57 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
TEM Progression fron M3-M12: Yes (n=67, 83)
|
41 Participants
|
26 Participants
|
—
|
—
|
|
Risk Factors of IF/TA Progression
TEM Progression fron M3-M12: Missing (n=67, 83)
|
0 Participants
|
3 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Percentage of IF measured by numerical quantification. The IF percentage was transposed in grade according to the following rule: grade 0 for an IF % ≤5%, grade I for an IF % ranging from \>5% to \< 25%, grade II for an IF % ranging from 25 to 50%, grade III for an IF % \>50%. Interstitial graft fibrosis has been identified as the primary cause of graft loss following death with a functional graft \[3-5\].
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change in Percentage of Interstitial Fibrosis (IF) by Numerical Quantification
Percentage of IF at M3 (n=26,43,32,53)
|
22.8 Percentage of IF
Standard Deviation 8.9
|
15.9 Percentage of IF
Standard Deviation 7.5
|
23.4 Percentage of IF
Standard Deviation 9.5
|
17.8 Percentage of IF
Standard Deviation 8.2
|
|
Change in Percentage of Interstitial Fibrosis (IF) by Numerical Quantification
Percentage of IF at M12 (n=24,42,32,53)
|
27.6 Percentage of IF
Standard Deviation 12.2
|
20.9 Percentage of IF
Standard Deviation 10.1
|
27.4 Percentage of IF
Standard Deviation 11.5
|
20.4 Percentage of IF
Standard Deviation 9.1
|
|
Change in Percentage of Interstitial Fibrosis (IF) by Numerical Quantification
Change in Percentage of IF (n=24,42,32,53)
|
5.1 Percentage of IF
Standard Deviation 12.4
|
4.9 Percentage of IF
Standard Deviation 12.2
|
3.9 Percentage of IF
Standard Deviation 12.3
|
2.7 Percentage of IF
Standard Deviation 9.7
|
SECONDARY outcome
Timeframe: M3 to M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Comparisons according to epithelial-mesenchymal transition (EMT) profile and immunosuppressive treatment
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Number of Participants With Progression of Renal Fibrosis Using Numerical Quantification
Fibrosis progression - Missing (n=24, 42, 31, 53)
|
2 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Progression of Renal Fibrosis Using Numerical Quantification
Fibrosis Progression - No (n=24, 42, 31, 53)
|
18 Participants
|
30 Participants
|
19 Participants
|
42 Participants
|
|
Number of Participants With Progression of Renal Fibrosis Using Numerical Quantification
Fibrosis progression - Yes (n=24, 42,31,43)
|
6 Participants
|
12 Participants
|
12 Participants
|
11 Participants
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Incidence and severity of EMT status. EMT status was determined centrally using the graft biopsy taken at 3 months. The result was quickly obtained (within 7 to 15 days) and sent to the company in charge of randomization in order to allocate each patient to a treatment group and to provide the investigator with this information without confirming EMT status.
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M3-Negative (n=26,43,32,53)
|
0 Participants
|
43 Participants
|
0 Participants
|
53 Participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M3- Positive (n=26,43,32,53)
|
26 Participants
|
0 Participants
|
32 Participants
|
0 Participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M3 - Not done (n=26,43,32,53)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M12- Negative (n=25,41,32,53)
|
8 Participants
|
24 Participants
|
9 Participants
|
36 Participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M12- Positive (n=25,41,32,53)
|
17 Participants
|
17 Participants
|
23 Participants
|
17 Participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Status
EMT Status at M12- Not done (n=25,41,32,53)
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Incidence and severity of EMT score. The intensity of EMT markers expression present and detectable in the renal graft at an early stage following transplantation is known as EMT score. EMT score 0 (the best): \<1 EMT score 1 (the better): 1-10% of tubular atrophy EMT score 2: 10-25% of tubular atrophy EMT score 3: 25-50% of tubular atrophy EMT score 4 (the worst): \>50% of tubular atrophy
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 0 at M3 (n= 26,43,32, 53)
|
0 participants
0.49
|
26 participants
0.49
|
0 participants
0.72
|
28 participants
0.5
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 1 at M3 (n= 26,43,32, 53)
|
0 participants
|
17 participants
|
0 participants
|
25 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 2 at M3 (n= 26,43,32, 53)
|
17 participants
|
0 participants
|
20 participants
|
0 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 3 at M3 (n= 26,43,32, 53)
|
9 participants
|
0 participants
|
8 participants
|
0 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 4 at M3 (n= 26,43,32, 53)
|
0 participants
|
0 participants
|
4 participants
|
0 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 0 at M12 (n= 25,41,32, 53)
|
1 participants
1.06
|
13 participants
1.17
|
0 participants
1.02
|
19 participants
1.03
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 1 at M12 (n= 25,41,32, 53)
|
7 participants
|
11 participants
|
9 participants
|
17 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 2 at M12 (n= 25,41,32, 53)
|
10 participants
|
11 participants
|
10 participants
|
12 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 3 at M12 (n= 25,41,32, 53)
|
4 participants
|
4 participants
|
9 participants
|
4 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Score 4 at M12 (n= 25,41,32, 53)
|
3 participants
|
2 participants
|
4 participants
|
1 participants
|
|
Number of Participants With Epithelial-mesenchymal Transition (EMT) Score
EMT Missing Score at M12 (n= 25,41,32, 53)
|
1 participants
|
2 participants
|
0 participants
|
0 participants
|
SECONDARY outcome
Timeframe: M3 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment. Among the 194 participants in the ITT group, 58 patients in the EMT+ group completed the study providing a graft biopsy for analysis at M3 and M12.
Change (M12 - M3) in EMT Score. Progression in EMT score is defined as an increase by \>=1 of EMT score from M3 to M12. EMT score 0 (the best): \<1 EMT score 1 (the better) : 1-10% of tubular atrophy EMT score 2 : 10-25% of tubular atrophy EMT score 3 : 25-50% of tubular atrophy EMT score 4 (the worst): \>50% of tubular atrophy
Outcome measures
| Measure |
Certican EMT+
n=26 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=43 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=32 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change in EMT Score
|
-0.3 scores on a scale
Standard Deviation 1.22
|
0.9 scores on a scale
Standard Deviation 1.09
|
-0.3 scores on a scale
Standard Deviation 1.05
|
0.6 scores on a scale
Standard Deviation 0.99
|
SECONDARY outcome
Timeframe: M3Population: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
Incidence of subclinical rejections and borderline lesions with regards to histological evidence of rejection with clinical findings. Subclinical rejections: rejection without clinical symptoms which is diagnosed by chance when a graft biopsy is performed. Clinically suspected BPAR: rejection suspected because of the presence of clinical symptoms (fever, pain, increase of creatinine) and then confirmed by the graft biopsy. Borderline lesions: suspicious for acute T-cell mediated rejection. This category is used when no intimal arteritis is present, but there are foci of tubulitis with minor interstitial infiltration or interstitial infiltration with mild tubulitis.
Outcome measures
| Measure |
Certican EMT+
n=69 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=85 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Subclinical rejections-No (n=68, 84)
|
67 Participants
|
84 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Subclinical rejections- Yes (n=68, 84)
|
1 Participants
|
0 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Subclinical rejections- missing (n=68, 84)
|
1 Participants
|
1 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Clinically suspected BPAR - No (N=68, 84)
|
68 Participants
|
84 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Clinically suspected BPAR - Yes (N=68, 84)
|
0 Participants
|
0 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Clinically suspected BPAR - Missing (N=68, 84)
|
1 Participants
|
1 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Borderline lesions - No (n=68,84)
|
62 Participants
|
71 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Borderline lesions - Yes (n=68,84)
|
6 Participants
|
13 Participants
|
—
|
—
|
|
Incidence (Number) of Subclinical Rejections and Borderline Lesions
Borderline lesions - Missing (n=68,84)
|
1 Participants
|
1 Participants
|
—
|
—
|
SECONDARY outcome
Timeframe: M3 (baseline) to M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
eGFR was calculated according to the abbreviated Modification of Diet in Renal Disease (MDRD) Formula and creatinine clearance according to the Cockcroft-Gault formula (mL/min/1.73m²). LOCF = Last observation carried forward
Outcome measures
| Measure |
Certican EMT+
n=71 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=87 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change From Baseline (M3) in Estimated Glomerular Filtration Rate (eGFR)
without imputation
|
6.99 mL/min/1.73m^2
Standard Error 1.66
|
2.54 mL/min/1.73m^2
Standard Error 1.5
|
—
|
—
|
|
Change From Baseline (M3) in Estimated Glomerular Filtration Rate (eGFR)
imputation by LOCF(96, 97)
|
5.96 mL/min/1.73m^2
Standard Error 1.39
|
2.15 mL/min/1.73m^2
Standard Error 1.37
|
—
|
—
|
SECONDARY outcome
Timeframe: Baseline (M3), M12Population: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
The average patient renal function was evaluated on the basis of eGFR was calculated according to the abbreviated MDRD formula and creatinine clearance according to the Cockcroft-Gault formula (mL/min/1.73m²).
Outcome measures
| Measure |
Certican EMT+
n=27 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=44 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=34 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=53 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change in Estimated Glomerular Filtration Rate (eGFR) at M12 From Baseline (M3) - ANCOVA Model
without imputation
|
8.6 mL/min/1.73m²
Standard Deviation 15.21
|
5.6 mL/min/1.73m²
Standard Deviation 18.73
|
1.5 mL/min/1.73m²
Standard Deviation 9.49
|
3.8 mL/min/1.73m²
Standard Deviation 10.99
|
|
Change in Estimated Glomerular Filtration Rate (eGFR) at M12 From Baseline (M3) - ANCOVA Model
imputation by LOCF (36, 60, 39, 58)
|
-11.9 mL/min/1.73m²
Standard Deviation 27.78
|
27.3 mL/min/1.73m²
Standard Deviation 138.44
|
5.1 mL/min/1.73m²
Standard Deviation 40.80
|
-4.9 mL/min/1.73m²
Standard Deviation 29.09
|
SECONDARY outcome
Timeframe: Month 3 (baseline), Month 12Population: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
One of the factors associated with EMT progression between M3 and M12 according to univariate analysis (ITT biopsies M3 \& M12).
Outcome measures
| Measure |
Certican EMT+
n=17 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=28 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=19 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=36 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Change in Urine Protein/Creatinine Ratio (Without Imputation)
|
44.4 mg/mmol
Standard Deviation 188.99
|
3.5 mg/mmol
Standard Deviation 48.37
|
16.0 mg/mmol
Standard Deviation 41.53
|
29.8 mg/mmol
Standard Deviation 189.41
|
SECONDARY outcome
Timeframe: M6 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
A treatment failure is defined as biopsy proven acute rejection (BPAR), a graft loss, a death or a loss to follow up. It was assessed between randomization and 6 and 12 months post-transplantation.
Outcome measures
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=60 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Treatment Failures
M12: Loss to follow-up - No
|
36 Number of Participants
|
59 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: Treatment Failure- No
|
33 Number of Participants
|
52 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: Treatment Failure- Yes
|
3 Number of Participants
|
8 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M12: Treatment Failure- No
|
29 Number of Participants
|
42 Number of Participants
|
36 Number of Participants
|
56 Number of Participants
|
|
Treatment Failures
M12: Treatment Failure- Yes
|
7 Number of Participants
|
18 Number of Participants
|
3 Number of Participants
|
3 Number of Participants
|
|
Treatment Failures
M6: BPAR - No
|
33 Number of Participants
|
52 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: BPAR -Yes
|
3 Number of Participants
|
8 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M12: BPAR - No
|
29 Number of Participants
|
43 Number of Participants
|
37 Number of Participants
|
56 Number of Participants
|
|
Treatment Failures
M12: BPAR - Yes
|
7 Number of Participants
|
17 Number of Participants
|
2 Number of Participants
|
3 Number of Participants
|
|
Treatment Failures
M6: Graft Loss - No
|
36 Number of Participants
|
60 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: Graft Loss - Yes
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M12: Graft Loss - No
|
35 Number of Participants
|
56 Number of Participants
|
38 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M12: Graft Loss - Yes
|
1 Number of Participants
|
4 Number of Participants
|
1 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M6: Death - No
|
36 Number of Participants
|
60 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: Death - Yes
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M12: Death - No
|
36 Number of Participants
|
60 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M12: Death - Yes
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M6: Loss to follow-up - No
|
36 Number of Participants
|
60 Number of Participants
|
39 Number of Participants
|
59 Number of Participants
|
|
Treatment Failures
M6: Loss to follow-up - Yes
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
|
Treatment Failures
M12: Loss to follow-up - Yes
|
0 Number of Participants
|
1 Number of Participants
|
0 Number of Participants
|
0 Number of Participants
|
SECONDARY outcome
Timeframe: M6 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system. Biopsy graded IA: Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IB: Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising \> 25% of the lumenal area. Biopsy graded III: Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation).
Outcome measures
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=60 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Type of Biopsy Proven Acute Rejection (BPAR)
Cellular AR - No
|
30 Participants
|
46 Participants
|
38 Participants
|
58 Participants
|
|
Type of Biopsy Proven Acute Rejection (BPAR)
Cellular AR - Yes
|
6 Participants
|
14 Participants
|
1 Participants
|
1 Participants
|
SECONDARY outcome
Timeframe: M6 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system. Biopsy graded IA: Significant interstitial infiltration (\> 25% of parenchyma) and foci of moderate tubulitis (\> 4 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IB: Significant interstitial infiltration (\> 25% of parenchyma) and foci of severe tubulitis (\> 10 mononuclear cells/tubular cross section or group of 10 tubular cells). Biopsy grade IIA: Mild to moderate intimal arteritis. Biopsy graded IIB: Severe intimal arteritis comprising \> 25% of the lumenal area. Biopsy graded III: Transmural (full vessel wall thickness) arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells (with accompanying lymphocytic inflammation).
Outcome measures
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=60 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Severity of BPAR
M6: Banff type Grade IA
|
0 Participants
|
2 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M6: Banff type Grade IB
|
0 Participants
|
4 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M6: Banff type Grade IIA
|
1 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M6: Banff type Grade IIB
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M6: Banff type Grade III
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M12: Banff type Grade IA
|
2 Participants
|
7 Participants
|
1 Participants
|
0 Participants
|
|
Severity of BPAR
M12: Banff type Grade IB
|
2 Participants
|
5 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M12: Banff type Grade IIA
|
1 Participants
|
1 Participants
|
0 Participants
|
1 Participants
|
|
Severity of BPAR
M12: Banff type Grade IIB
|
0 Participants
|
1 Participants
|
0 Participants
|
0 Participants
|
|
Severity of BPAR
M12: Banff type Grade III
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
SECONDARY outcome
Timeframe: M6 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
A biopsy proven acute rejection (BPAR) is defined as a biopsy graded IA, IB, IIA, IIB or III as per 2005/2007 Banff histological classification system.
Outcome measures
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=60 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Incidence (Number) of BPAR
M6 - No
|
33 Number of participants
|
52 Number of participants
|
39 Number of participants
|
59 Number of participants
|
|
Incidence (Number) of BPAR
M6 - Yes
|
3 Number of participants
|
8 Number of participants
|
0 Number of participants
|
0 Number of participants
|
|
Incidence (Number) of BPAR
M12 - No
|
29 Number of participants
|
43 Number of participants
|
37 Number of participants
|
56 Number of participants
|
|
Incidence (Number) of BPAR
M12 - Yes
|
7 Number of participants
|
17 Number of participants
|
2 Number of participants
|
3 Number of participants
|
SECONDARY outcome
Timeframe: M6 and M12 post transplantationPopulation: ITT population: All patients randomized in the study who received at least one dose of the study treatment.
If a participant underwent a graft nephrectomy, then the day of nephrectomy was considered as the day of graft loss.
Outcome measures
| Measure |
Certican EMT+
n=36 Participants
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
Neoral EMT+
n=60 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT+
n=39 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Neoral EMT-
n=59 Participants
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
|---|---|---|---|---|
|
Incidence (Number) of Participants With Graft Losses
M12 - No
|
35 Participants
|
56 Participants
|
38 Participants
|
59 Participants
|
|
Incidence (Number) of Participants With Graft Losses
M6 - No
|
36 Participants
|
60 Participants
|
39 Participants
|
59 Participants
|
|
Incidence (Number) of Participants With Graft Losses
M6 - Yes
|
0 Participants
|
0 Participants
|
0 Participants
|
0 Participants
|
|
Incidence (Number) of Participants With Graft Losses
M12 - Yes
|
1 Participants
|
4 Participants
|
1 Participants
|
0 Participants
|
Adverse Events
Neoral
Serious events: 39 serious events
Other events: 59 other events
Deaths: 0 deaths
Certican
Serious events: 46 serious events
Other events: 59 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Neoral
n=98 participants at risk
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Certican
n=96 participants at risk
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
|---|---|---|
|
Immune system disorders
Amyloidosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Immune system disorders
Kidney transplant rejection
|
0.00%
0/98
|
4.2%
4/96
|
|
Immune system disorders
Transplant rejection
|
1.0%
1/98
|
0.00%
0/96
|
|
Blood and lymphatic system disorders
Agranulocytosis
|
0.00%
0/98
|
1.0%
1/96
|
|
Blood and lymphatic system disorders
Anaemia
|
1.0%
1/98
|
2.1%
2/96
|
|
Blood and lymphatic system disorders
Febrile neutropenia
|
0.00%
0/98
|
1.0%
1/96
|
|
Blood and lymphatic system disorders
Leukopenia
|
1.0%
1/98
|
0.00%
0/96
|
|
Blood and lymphatic system disorders
Neutropenia
|
2.0%
2/98
|
0.00%
0/96
|
|
Blood and lymphatic system disorders
Pancytopenia
|
2.0%
2/98
|
0.00%
0/96
|
|
Cardiac disorders
Acute coronary syndrome
|
1.0%
1/98
|
0.00%
0/96
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
1.0%
1/98
|
2.1%
2/96
|
|
Gastrointestinal disorders
Colitis
|
0.00%
0/98
|
2.1%
2/96
|
|
Gastrointestinal disorders
Colitis ulcerative
|
0.00%
0/98
|
1.0%
1/96
|
|
Gastrointestinal disorders
Dental necrosis
|
0.00%
0/98
|
1.0%
1/96
|
|
Gastrointestinal disorders
Diarrhoea
|
3.1%
3/98
|
3.1%
3/96
|
|
Gastrointestinal disorders
Gastritis
|
1.0%
1/98
|
0.00%
0/96
|
|
Gastrointestinal disorders
Hernial eventration
|
0.00%
0/98
|
1.0%
1/96
|
|
Gastrointestinal disorders
Oesophageal ulcer
|
1.0%
1/98
|
0.00%
0/96
|
|
Gastrointestinal disorders
Periodontitis
|
0.00%
0/98
|
1.0%
1/96
|
|
General disorders
Asthenia
|
1.0%
1/98
|
1.0%
1/96
|
|
General disorders
Chills
|
1.0%
1/98
|
0.00%
0/96
|
|
General disorders
General physical health deterioration
|
0.00%
0/98
|
1.0%
1/96
|
|
General disorders
Hyperthermia
|
1.0%
1/98
|
1.0%
1/96
|
|
General disorders
Oedema peripheral
|
0.00%
0/98
|
1.0%
1/96
|
|
General disorders
Pain
|
1.0%
1/98
|
0.00%
0/96
|
|
General disorders
Pyrexia
|
5.1%
5/98
|
5.2%
5/96
|
|
General disorders
Sudden death
|
1.0%
1/98
|
0.00%
0/96
|
|
Hepatobiliary disorders
Hepatitis
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Abdominal abscess
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Bacillus infection
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Bacterial pyelonephritis
|
3.1%
3/98
|
2.1%
2/96
|
|
Infections and infestations
Bronchitis
|
0.00%
0/98
|
2.1%
2/96
|
|
Infections and infestations
Cytomegalovirus infection
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Diarrhoea infectious
|
0.00%
0/98
|
2.1%
2/96
|
|
Infections and infestations
Escherichia bacteraemia
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Escherichia infection
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Eye infection toxoplasmal
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Gastroenteritis
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Gastroenteritis yersinia
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Hepatic cyst infection
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Lung infection
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Orchitis
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Pneumocystis jiroveci pneumonia
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Pneumonia
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Polyomavirus-associated nephropathy
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Pseudomonal sepsis
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Pyelonephritis
|
2.0%
2/98
|
3.1%
3/96
|
|
Infections and infestations
Pyelonephritis acute
|
1.0%
1/98
|
3.1%
3/96
|
|
Infections and infestations
Renal cyst infection
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Sinusitis
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Staphylococcal infection
|
1.0%
1/98
|
0.00%
0/96
|
|
Infections and infestations
Transplant abscess
|
0.00%
0/98
|
1.0%
1/96
|
|
Infections and infestations
Urinary tract infection
|
2.0%
2/98
|
4.2%
4/96
|
|
Infections and infestations
Viral pharyngitis
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Accidental overdose
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula site complication
|
0.00%
0/98
|
1.0%
1/96
|
|
Injury, poisoning and procedural complications
Arteriovenous fistula thrombosis
|
2.0%
2/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Graft loss
|
1.0%
1/98
|
1.0%
1/96
|
|
Injury, poisoning and procedural complications
Head injury
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Overdose
|
1.0%
1/98
|
2.1%
2/96
|
|
Injury, poisoning and procedural complications
Post procedural haematuria
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Spinal fracture
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Toxicity to various agents
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Ureteric anastomosis complication
|
1.0%
1/98
|
0.00%
0/96
|
|
Injury, poisoning and procedural complications
Vascular graft complication
|
1.0%
1/98
|
0.00%
0/96
|
|
Investigations
Blood creatinine increased
|
3.1%
3/98
|
2.1%
2/96
|
|
Investigations
Blood pressure increased
|
0.00%
0/98
|
1.0%
1/96
|
|
Investigations
Weight decreased
|
0.00%
0/98
|
2.1%
2/96
|
|
Metabolism and nutrition disorders
Diabetes mellitus inadequate control
|
1.0%
1/98
|
0.00%
0/96
|
|
Metabolism and nutrition disorders
Gout
|
1.0%
1/98
|
0.00%
0/96
|
|
Metabolism and nutrition disorders
Hypercreatininaemia
|
1.0%
1/98
|
1.0%
1/96
|
|
Metabolism and nutrition disorders
Hypoglycaemia
|
1.0%
1/98
|
0.00%
0/96
|
|
Metabolism and nutrition disorders
Malnutrition
|
1.0%
1/98
|
0.00%
0/96
|
|
Musculoskeletal and connective tissue disorders
Fistula
|
1.0%
1/98
|
0.00%
0/96
|
|
Musculoskeletal and connective tissue disorders
Pain in extremity
|
1.0%
1/98
|
0.00%
0/96
|
|
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Multiple myeloma
|
1.0%
1/98
|
0.00%
0/96
|
|
Nervous system disorders
Cerebrovascular accident
|
0.00%
0/98
|
1.0%
1/96
|
|
Nervous system disorders
Dizziness
|
1.0%
1/98
|
0.00%
0/96
|
|
Nervous system disorders
Headache
|
1.0%
1/98
|
0.00%
0/96
|
|
Nervous system disorders
Status epilepticus
|
1.0%
1/98
|
0.00%
0/96
|
|
Nervous system disorders
Syncope
|
1.0%
1/98
|
0.00%
0/96
|
|
Psychiatric disorders
Depression
|
1.0%
1/98
|
1.0%
1/96
|
|
Psychiatric disorders
Neurosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Glomerulonephritis
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Haematuria
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Hydronephrosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Proteinuria
|
1.0%
1/98
|
1.0%
1/96
|
|
Renal and urinary disorders
Renal failure acute
|
4.1%
4/98
|
2.1%
2/96
|
|
Renal and urinary disorders
Renal tubular disorder
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Renal tubular necrosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Renal and urinary disorders
Vesicoureteric reflux
|
0.00%
0/98
|
1.0%
1/96
|
|
Reproductive system and breast disorders
Metrorrhagia
|
1.0%
1/98
|
0.00%
0/96
|
|
Reproductive system and breast disorders
Prostatitis
|
1.0%
1/98
|
0.00%
0/96
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
0.00%
0/98
|
1.0%
1/96
|
|
Respiratory, thoracic and mediastinal disorders
Dyspnoea
|
0.00%
0/98
|
2.1%
2/96
|
|
Respiratory, thoracic and mediastinal disorders
Lung disorder
|
1.0%
1/98
|
1.0%
1/96
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.00%
0/98
|
2.1%
2/96
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory distress
|
0.00%
0/98
|
1.0%
1/96
|
|
Skin and subcutaneous tissue disorders
Capillaritis
|
1.0%
1/98
|
0.00%
0/96
|
|
Skin and subcutaneous tissue disorders
Rash maculo-papular
|
0.00%
0/98
|
1.0%
1/96
|
|
Surgical and medical procedures
Hip arthroplasty
|
0.00%
0/98
|
1.0%
1/96
|
|
Vascular disorders
Haematoma
|
1.0%
1/98
|
0.00%
0/96
|
|
Vascular disorders
Haemorrhage
|
0.00%
0/98
|
1.0%
1/96
|
|
Vascular disorders
Iliac artery stenosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Vascular disorders
Orthostatic hypotension
|
1.0%
1/98
|
0.00%
0/96
|
|
Vascular disorders
Phlebitis
|
0.00%
0/98
|
1.0%
1/96
|
|
Vascular disorders
Subclavian artery stenosis
|
1.0%
1/98
|
0.00%
0/96
|
|
Vascular disorders
Venous thrombosis limb
|
1.0%
1/98
|
0.00%
0/96
|
Other adverse events
| Measure |
Neoral
n=98 participants at risk
Between transplantation and randomization, all patients have received Neoral®. Treatment had to be initiated within 24 hours post-transplantation in combination with Myfortic®.
|
Certican
n=96 participants at risk
Patients randomized to the Certican® treatment group started this treatment after randomization (which took place 3 to 4 months post-transplantation), preferably in the evening, otherwise the following morning. Patients in the Neoral® treatment group did not receive Certican®.
|
|---|---|---|
|
Blood and lymphatic system disorders
Anaemia
|
6.1%
6/98
|
7.3%
7/96
|
|
Blood and lymphatic system disorders
Leukopenia
|
7.1%
7/98
|
2.1%
2/96
|
|
Blood and lymphatic system disorders
Neutropenia
|
6.1%
6/98
|
6.2%
6/96
|
|
Gastrointestinal disorders
Aphthous stomatitis
|
3.1%
3/98
|
17.7%
17/96
|
|
Gastrointestinal disorders
Diarrhoea
|
3.1%
3/98
|
7.3%
7/96
|
|
Gastrointestinal disorders
Gingival hypertrophy
|
8.2%
8/98
|
0.00%
0/96
|
|
General disorders
Oedema peripheral
|
17.3%
17/98
|
14.6%
14/96
|
|
Infections and infestations
Bronchitis
|
6.1%
6/98
|
5.2%
5/96
|
|
Infections and infestations
Cytomegalovirus infection
|
7.1%
7/98
|
2.1%
2/96
|
|
Infections and infestations
Urinary tract infection
|
5.1%
5/98
|
7.3%
7/96
|
|
Metabolism and nutrition disorders
Dyslipidaemia
|
6.1%
6/98
|
9.4%
9/96
|
|
Respiratory, thoracic and mediastinal disorders
Cough
|
5.1%
5/98
|
1.0%
1/96
|
|
Skin and subcutaneous tissue disorders
Acne
|
1.0%
1/98
|
6.2%
6/96
|
|
Skin and subcutaneous tissue disorders
Rash
|
0.00%
0/98
|
7.3%
7/96
|
|
Vascular disorders
Hypertension
|
6.1%
6/98
|
5.2%
5/96
|
Additional Information
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 pooled data (i.e.,data from all sites) in clinical trial or disclosure of trial results in their entirety.
- Publication restrictions are in place
Restriction type: OTHER