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Campath, Calcineurin Inhibitor Reduction and Chronic Allograft Nephropathy (3C)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01120028
Recruitment Status : Active, not recruiting
First Posted : May 10, 2010
Results First Posted : October 1, 2019
Last Update Posted : October 1, 2019
Sponsor:
Collaborators:
National Health Service, United Kingdom
Pfizer
Novartis
Information provided by (Responsible Party):
University of Oxford

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Factorial Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Kidney Transplantation
Interventions Drug: Alemtuzumab
Drug: Basiliximab
Drug: Sirolimus
Drug: Tacrolimus
Enrollment 852
Recruitment Details 3C was conducted in 18 transplant centres in the UK. Recruitment took place between October 2010 and July 2013.
Pre-assignment Details 852 participants were randomized for a comparison of Alemtuzumab (426) and Basiliximab (426) based induction therapies. After 6-months, 394 of those participants were re-randomized to either Sirolimus (197) or Tacrolimus (197) based maintenance therapies.
Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description

Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab

Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Period Title: Period 1: Alemtuzumab or Basiliximab
Started 426 426 0 0
Completed 412 403 0 0
Not Completed 14 23 0 0
Reason Not Completed
Withdrawal by Subject             0             5             0             0
Not transplanted             14             18             0             0
Period Title: Period 2: Tacrolimus or Sirolimus
Started 0 0 197 197
Completed 0 0 197 197
Not Completed 0 0 0 0
Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus Total
Hide Arm/Group Description

Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart.

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart.

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab.

Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL. Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL. Total of all reporting groups
Overall Number of Baseline Participants 426 426 197 197 1246
Hide Baseline Analysis Population Description
Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab). Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).
Age, Categorical   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Age, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
<=18 years
0
   0.0%
0
   0.0%
0 0
0
   0.0%
Between 18 and 65 years
347
  81.5%
350
  82.2%
0 0
697
  81.8%
>=65 years
79
  18.5%
76
  17.8%
0 0
155
  18.2%
Age, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
<=18 years 0 0
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years 0 0
163
  82.7%
162
  82.2%
325
  82.5%
>=65 years 0 0
34
  17.3%
35
  17.8%
69
  17.5%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Age, Continuous   [1] 
Mean (Standard Deviation)
Unit of measure:  Years
Age, Continuous, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
52.1  (13.3) 51.8  (13.3) 51.9  (13.3)
Age, Continuous, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
51.7  (13.0) 52.0  (12.9) 51.8  (13.0)
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Sex: Female, Male   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Sex, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Female
149
  35.0%
151
  35.4%
0 0
300
  35.2%
Male
277
  65.0%
275
  64.6%
0 0
552
  64.8%
Sex, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
Female 0 0
65
  33.0%
65
  33.0%
130
  33.0%
Male 0 0
132
  67.0%
132
  67.0%
264
  67.0%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Race/Ethnicity, Customized   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Ethnic origin, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
White
370
  86.9%
372
  87.3%
0 0
742
  87.1%
Black
21
   4.9%
21
   4.9%
0 0
42
   4.9%
Asian
30
   7.0%
23
   5.4%
0 0
53
   6.2%
Other
5
   1.2%
10
   2.3%
0 0
15
   1.8%
Ethnic origin, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
White 0 0
174
  88.3%
173
  87.8%
347
  88.1%
Black 0 0
5
   2.5%
7
   3.6%
12
   3.0%
Asian 0 0
13
   6.6%
15
   7.6%
28
   7.1%
Other 0 0
5
   2.5%
2
   1.0%
7
   1.8%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Region of Enrollment   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
United Kingdom Number Analyzed 426 participants 426 participants 197 participants 197 participants 1246 participants
Period 1: United Kingdom
426
 100.0%
426
 100.0%
0
   0.0%
0
   0.0%
852
  68.4%
Period 2: United Kingdom
0
   0.0%
0
   0.0%
197
 100.0%
197
 100.0%
394
  31.6%
[1]
Measure Description: All 852 participants were recruited in the UK.
[2]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Primary Renal Disease   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Primary Renal Disease: Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Diabetic kidney disease
51
  12.0%
49
  11.5%
0 0
100
  11.7%
Glomerulonephritis
92
  21.6%
89
  20.9%
0 0
181
  21.2%
Polycystic kidney disease
68
  16.0%
73
  17.1%
0 0
141
  16.5%
Chronic pyelonephritis
23
   5.4%
16
   3.8%
0 0
39
   4.6%
Hypertension
42
   9.9%
42
   9.9%
0 0
84
   9.9%
Renovascular disease
7
   1.6%
6
   1.4%
0 0
13
   1.5%
Other
143
  33.6%
151
  35.4%
0 0
294
  34.5%
Primary renal disease, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
Diabetic kidney disease 0 0
15
   7.6%
21
  10.7%
36
   9.1%
Glomerulonephritis 0 0
50
  25.4%
40
  20.3%
90
  22.8%
Polycystic kidney disease 0 0
47
  23.9%
34
  17.3%
81
  20.6%
Chronic pyelonephritis 0 0
5
   2.5%
9
   4.6%
14
   3.6%
Hypertension 0 0
14
   7.1%
24
  12.2%
38
   9.6%
Renovascular disease 0 0
3
   1.5%
4
   2.0%
7
   1.8%
Other 0 0
63
  32.0%
65
  33.0%
128
  32.5%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Other Previous Disease   [1] 
Measure Type: Number
Unit of measure:  Participants
Diabetes Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
74 67 141
Vascular Disease Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
57 49 106
Cancer Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
18 5 23
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Previous renal replacement   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Haemodialysis
243
  57.0%
214
  50.2%
0 0
457
  53.6%
Peritoneal dialysis
104
  24.4%
106
  24.9%
0 0
210
  24.6%
Transplant
3
   0.7%
3
   0.7%
0 0
6
   0.7%
None
76
  17.8%
103
  24.2%
0 0
179
  21.0%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

HLA mismatch level   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
HLA mismatch level, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Level 1
45
  10.6%
47
  11.0%
0 0
92
  10.8%
Level 2
94
  22.1%
94
  22.1%
0 0
188
  22.1%
Level 3
196
  46.0%
193
  45.3%
0 0
389
  45.7%
Level 4
91
  21.4%
92
  21.6%
0 0
183
  21.5%
HLA mismatch level, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
Level 1 0 0
23
  11.7%
22
  11.2%
45
  11.4%
Level 2 0 0
42
  21.3%
42
  21.3%
84
  21.3%
Level 3 0 0
89
  45.2%
90
  45.7%
179
  45.4%
Level 4 0 0
43
  21.8%
43
  21.8%
86
  21.8%
[1]
Measure Description:

HLA = human leucocyte antigen.

Level 1: 0-0-0; Level 2: 0 HLA-DR and 0/1 HLA-B mismatches; Level 3: (0 HLA-DR and 2 HLA-B) or (1 HLA-DR and 0/1 HLA-B); Level 4: (1 HLA-DR and 2 HLA-B) or (2 HLA-DR).

Level 1 being most favourable, Level 4 being least favourable.

[2]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Previous transplant   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Previous transplant, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
None
390
  91.5%
392
  92.0%
0 0
782
  91.8%
≥1
36
   8.5%
34
   8.0%
0 0
70
   8.2%
Previous transplant, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
None 0 0
181
  91.9%
181
  91.9%
362
  91.9%
≥1 0 0
16
   8.1%
16
   8.1%
32
   8.1%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Highly sensitised   [1] [2] 
Measure Type: Count of Participants
Unit of measure:  Participants
Highly sensitized, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Yes
16
   3.8%
15
   3.5%
0 0
31
   3.6%
No
410
  96.2%
411
  96.5%
0 0
821
  96.4%
Highly sensitized, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
Yes 0 0
4
   2.0%
7
   3.6%
11
   2.8%
No 0 0
193
  98.0%
190
  96.4%
383
  97.2%
[1]
Measure Description: Highly sensitised is defined as calculated reaction frequency >85% where the calculated reaction frequency is the proportion of the general UK population that the participant is predicted to be sensitised against.
[2]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Virology serology   [1] [2] 
Measure Type: Number
Unit of measure:  Participants
CMV-positive donor to negative recipient Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
104 102 206
EBV-positive donor to negative recipient Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
21 19 40
[1]
Measure Description: CMV=cytomegalovirus; EBV=Epstein-Barr virus.
[2]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Type of donor   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Type of donor, Period 1 Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Donation after brain death
148
  34.7%
145
  34.0%
0 0
293
  34.4%
Donation after circulatory death
158
  37.1%
158
  37.1%
0 0
316
  37.1%
Donation from living (related or unrelated) person
120
  28.2%
123
  28.9%
0 0
243
  28.5%
Type of donor, Period 2 Number Analyzed 0 participants 0 participants 197 participants 197 participants 394 participants
Donation after brain death 0 0
66
  33.5%
65
  33.0%
131
  33.2%
Donation after circulatory death 0 0
65
  33.0%
69
  35.0%
134
  34.0%
Donation from living (related or unrelated) person 0 0
66
  33.5%
63
  32.0%
129
  32.7%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Donor sex   [1] 
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
Male
215
  50.5%
207
  48.6%
0 0
422
  49.5%
Female
193
  45.3%
179
  42.0%
0 0
372
  43.7%
Unknown
18
   4.2%
40
   9.4%
0 0
58
   6.8%
[1]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

Cold ischaemia time (h)   [1] [2] 
Mean (Standard Deviation)
Unit of measure:  Hours
Number Analyzed 426 participants 426 participants 0 participants 0 participants 852 participants
13.9  (5.7) 12.9  (6.0) 13.4  (5.9)
[1]
Measure Description: For deceased donor transplants only.
[2]
Measure Analysis Population Description:

Period 1: Baseline data (852 participants) at randomization to induction therapy (Alemtuzumab or Basiliximab).

Period 2: 6-months post-transplantation, baseline data (394 of the original participants) at re-randomization to maintanence therapy (Sirolimus or Tacrolimus).

1.Primary Outcome
Title Number of Participants With Biopsy-proven Acute Rejection at 6-months After Randomization to Induction Therapy
Hide Description Occurence of biopsy-proven acute rejection events at 6-months after transplantation during Period 1 (randomization to induction therapy (Campath-1H and Tacrolimus, or Basiliximab and Tacrolimus))
Time Frame 6 months post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus
Hide Arm/Group Description:

Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab

Overall Number of Participants Analyzed 426 426
Measure Type: Count of Participants
Unit of Measure: Participants
31
   7.3%
68
  16.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.0001
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.42
Confidence Interval (2-Sided) 95%
0.28 to 0.64
Estimation Comments [Not Specified]
2.Primary Outcome
Title Graft Function (at 18-months After Randomization to Maintenance Therapy)
Hide Description Estimated glomerular filtration rate (estimated using MDRD formula) at 18-months after maintenance therapy randomization to either Sirolimus or Tacrolimus.
Time Frame 2 years post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description:
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Overall Number of Participants Analyzed 197 197
Mean (Standard Error)
Unit of Measure: mL/min/1.73m²
53.7  (0.9) 54.6  (0.9)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 2: Sirolimus, Period 2: Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5
Comments [Not Specified]
Method ANCOVA
Comments [Not Specified]
3.Secondary Outcome
Title Number of Participants With Graft Failure (at 6-months After Randomization to Induction Therapy)
Hide Description Return to dialysis or re-transplantation by 6-months after randomization to induction therapy.
Time Frame 6 months post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus
Hide Arm/Group Description:

Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab

Overall Number of Participants Analyzed 426 426
Measure Type: Count of Participants
Unit of Measure: Participants
16
   3.8%
13
   3.1%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Alemtuzumab/Tacrolimus, Period 1: Basiliximab/Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.58
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.23
Confidence Interval (2-Sided) 95%
0.59 to 2.55
Estimation Comments [Not Specified]
4.Secondary Outcome
Title Number of Participants With Graft Failure (at 18-Months After Randomization to Maintenance Therapy)
Hide Description Return to dialysis or re-transplantation by 18-months after randomization to maintenance therapy.
Time Frame 2 years post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description:
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Overall Number of Participants Analyzed 197 197
Measure Type: Count of Participants
Unit of Measure: Participants
8
   4.1%
4
   2.0%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 2: Sirolimus, Period 2: Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.23
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.99
Confidence Interval (2-Sided) 95%
0.64 to 6.18
Estimation Comments [Not Specified]
5.Secondary Outcome
Title Number of Participants With Serious Infection (at 6-months After Randomization to Induction Therapy)
Hide Description Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported within Period 1 (randomization to induction therapy of either Alemtuzumab (Campath-1H) and Tacrolimus, or Basiliximab and Tacrolimus).
Time Frame 6-months post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 1: Campath 1H/Tacrolimus Period 1: Basiliximab/Tacrolimus
Hide Arm/Group Description:

Induction therapy allocation: Campath-1H and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab

Overall Number of Participants Analyzed 426 426
Measure Type: Count of Participants
Unit of Measure: Participants
135
  31.7%
136
  31.9%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 1: Campath 1H/Tacrolimus, Period 1: Basiliximab/Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.88
Comments [Not Specified]
Method Regression, Cox
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.02
Confidence Interval (2-Sided) 95%
0.80 to 1.29
Estimation Comments [Not Specified]
6.Secondary Outcome
Title Number of Participants With Serious Infection (at 18-months After Randomization to Maintenance Therapy)
Hide Description Occurrence of any serious infection (opportunistic or requiring admission to hospital) reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Time Frame 2 years post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description:
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Overall Number of Participants Analyzed 197 197
Measure Type: Count of Participants
Unit of Measure: Participants
95
  48.2%
70
  35.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 2: Sirolimus, Period 2: Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.008
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate ratio
Estimated Value 1.51
Confidence Interval (2-Sided) 95%
1.11 to 2.06
Estimation Comments [Not Specified]
7.Secondary Outcome
Title Number of Participants With Cancer (at 18-months After Randomization to Maintenance Therapy)
Hide Description Occurrence of any cancer reported during Period 2 (maintenance therapy randomization to either Sirolimus or Tacrolimus).
Time Frame 2 years post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description:
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Overall Number of Participants Analyzed 197 197
Measure Type: Count of Participants
Unit of Measure: Participants
17
   8.6%
17
   8.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 2: Sirolimus, Period 2: Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.99
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 1.00
Confidence Interval (2-Sided) 95%
0.51 to 1.97
Estimation Comments [Not Specified]
8.Secondary Outcome
Title Number of Participants With Major Vascular Event (at 18-months After Randomization to Maintenance Therapy)
Hide Description Composite of non-fatal myocardial infarction, non-fatal stroke, cardiovascular death or arterial revascularization
Time Frame 2 years post-transplantation
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description:
Sirolimus maintenance therapy: target trough level of 6-12 ng/mL for the first 6-months, then reducing to 5-10 ng/mL.
Tacrolimus maintenance therapy: target trough level of 5-7 ng/mL
Overall Number of Participants Analyzed 197 197
Measure Type: Count of Participants
Unit of Measure: Participants
10
   5.1%
13
   6.6%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Period 2: Sirolimus, Period 2: Tacrolimus
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.52
Comments [Not Specified]
Method Log Rank
Comments [Not Specified]
Method of Estimation Estimation Parameter Rate Ratio
Estimated Value 0.76
Confidence Interval (2-Sided) 95%
0.34 to 1.73
Estimation Comments [Not Specified]
Time Frame Period 1: SAEs collected during the 6-months post-transplantation Period 2: SAEs collected between 6-months and 24-months post-transplantation
Adverse Event Reporting Description

Information about the occurrence of serious adverse events was recorded at scheduled visits

Other (not including Serious) Adverse Events were not recorded or assessed.

 
Arm/Group Title Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
Hide Arm/Group Description

Induction therapy allocation: Alemtuzumab (Campath-1H) and Tacrolimus

Alemtuzumab: Alemtuzumab 30 mg intravenously or subcutaneously, two doses 24 hours apart

Tacrolimus: Target trough level 5-7 ng/mL for 6-months after alemtuzumab.

Induction therapy allocation: Basiliximab and Tacrolimus

Basiliximab: 20 mg intravenously, two doses 96 hours apart

Tacrolimus: Target trough level 5-12 ng/mL for 6-months after basiliximab

Maintenance therapy allocation: Sirolimus

Target trough level of 6-12 ng/mL for the first 6-months then reducing to 5-10 ng/nL

Maintenancy therapy allocation: Tacrolimus

Target trough level of 5-7 ng/mL

All-Cause Mortality
Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   11/426 (2.58%)   6/426 (1.41%)   11/197 (5.58%)   9/197 (4.57%) 
Show Serious Adverse Events Hide Serious Adverse Events
Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   341/426 (80.05%)   354/426 (83.10%)   140/197 (71.07%)   134/197 (68.02%) 
Blood and lymphatic system disorders         
Blood and lymphatic system disorders  1  26/426 (6.10%)  15/426 (3.52%)  3/197 (1.52%)  7/197 (3.55%) 
Cardiac disorders         
Cardiac disorders  1  14/426 (3.29%)  15/426 (3.52%)  10/197 (5.08%)  3/197 (1.52%) 
Congenital, familial and genetic disorders         
Congenital, familial and genetic disorders  1  0/426 (0.00%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Ear and labyrinth disorders         
Ear and labyrinth disorders  1  1/426 (0.23%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Endocrine disorders         
Endocrine disorders  1  0/426 (0.00%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Eye disorders         
Eye disorders  1  0/426 (0.00%)  0/426 (0.00%)  1/197 (0.51%)  0/197 (0.00%) 
Gastrointestinal disorders         
Gastrointestinal disorders  1  39/426 (9.15%)  40/426 (9.39%)  27/197 (13.71%)  25/197 (12.69%) 
General disorders         
General disorders and administration site conditions  1  22/426 (5.16%)  13/426 (3.05%)  5/197 (2.54%)  2/197 (1.02%) 
Hepatobiliary disorders         
Hepatobiliary disorders  1  1/426 (0.23%)  1/426 (0.23%)  3/197 (1.52%)  2/197 (1.02%) 
Immune system disorders         
Immune system disorders  1  41/426 (9.62%)  70/426 (16.43%)  33/197 (16.75%)  9/197 (4.57%) 
Infections and infestations         
Infections and infestations  1  158/426 (37.09%)  161/426 (37.79%)  97/197 (49.24%)  74/197 (37.56%) 
Injury, poisoning and procedural complications         
Injury, poisoning and procedural complications  1  154/426 (36.15%)  131/426 (30.75%)  13/197 (6.60%)  7/197 (3.55%) 
Investigations         
Investigations  1  140/426 (32.86%)  136/426 (31.92%)  24/197 (12.18%)  26/197 (13.20%) 
Metabolism and nutrition disorders         
Metabolism and nutrition disorders  1  20/426 (4.69%)  23/426 (5.40%)  19/197 (9.64%)  18/197 (9.14%) 
Musculoskeletal and connective tissue disorders         
Musculoskeletal and connective tissue disorders  1  3/426 (0.70%)  3/426 (0.70%)  3/197 (1.52%)  4/197 (2.03%) 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Neoplasms benign, malignant and unspecified (incl cysts and polyps)  1  6/426 (1.41%)  7/426 (1.64%)  18/197 (9.14%)  17/197 (8.63%) 
Nervous system disorders         
Nervous system disorders  1  10/426 (2.35%)  13/426 (3.05%)  8/197 (4.06%)  13/197 (6.60%) 
Pregnancy, puerperium and perinatal conditions         
Pregnancy, puerperium and perinatal conditions  1  0/426 (0.00%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Psychiatric disorders         
Psychiatric disorders  1  5/426 (1.17%)  2/426 (0.47%)  0/197 (0.00%)  1/197 (0.51%) 
Renal and urinary disorders         
Renal and urinary disorders  1  24/426 (5.63%)  37/426 (8.69%)  7/197 (3.55%)  9/197 (4.57%) 
Reproductive system and breast disorders         
Reproductive system and breast disorders  1  1/426 (0.23%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Respiratory, thoracic and mediastinal disorders         
Respiratory, thoracic and mediastinal disorders  1  7/426 (1.64%)  15/426 (3.52%)  7/197 (3.55%)  4/197 (2.03%) 
Skin and subcutaneous tissue disorders         
Skin and subcutaneous tissue disorders  1  2/426 (0.47%)  1/426 (0.23%)  2/197 (1.02%)  4/197 (2.03%) 
Social circumstances         
Social circumstances  1  0/426 (0.00%)  0/426 (0.00%)  0/197 (0.00%)  0/197 (0.00%) 
Surgical and medical procedures         
Surgical and medical procedures  1  190/426 (44.60%)  190/426 (44.60%)  39/197 (19.80%)  35/197 (17.77%) 
Vascular disorders         
Vascular disorders  1  13/426 (3.05%)  14/426 (3.29%)  3/197 (1.52%)  2/197 (1.02%) 
1
Term from vocabulary, MedDRA (14.0)
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Period 1: Alemtuzumab/Tacrolimus Period 1: Basiliximab/Tacrolimus Period 2: Sirolimus Period 2: Tacrolimus
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   0/0   0/0   0/0   0/0 
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Prof Peter Friend
Organization: University of Oxford
Phone: 01865223872
EMail: ccc@ctsu.ox.ac.uk
Layout table for additonal information
Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01120028     History of Changes
Other Study ID Numbers: CTSU3C1
2008-008553-27 ( EudraCT Number )
ISRCTN88894088 ( Registry Identifier: ISRCTN )
First Submitted: May 6, 2010
First Posted: May 10, 2010
Results First Submitted: June 10, 2019
Results First Posted: October 1, 2019
Last Update Posted: October 1, 2019