Trial Outcomes & Findings for Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch (NCT NCT00275509)
NCT ID: NCT00275509
Last Updated: 2018-01-18
Results Overview
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising \>25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
COMPLETED
PHASE3
56 participants
Up to 6 months
2018-01-18
Participant Flow
A total of 207 participant were assessed for eligibility. Excluded (n=151) Not meeting inclusion criteria (n=115) Declined to participate (n=2) Did not reach transplant prior to end of study (n=34). A total of 56 were randomized.
Participant milestones
| Measure |
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
|
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
Overall Study
STARTED
|
30
|
26
|
|
Overall Study
COMPLETED
|
30
|
25
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Thymoglobulin
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6.
|
Daclizumab
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
Overall Study
graft thrombosis, post-operative day #8
|
0
|
1
|
Baseline Characteristics
Induction Therapy Study in Live Donor Kidney Transplant Recipients With a Positive Crossmatch
Baseline characteristics by cohort
| Measure |
Tymoglobulin
n=30 Participants
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 Participants
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
Total
n=56 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
48.2 years
STANDARD_DEVIATION 10.6 • n=5 Participants
|
46.5 years
STANDARD_DEVIATION 15.4 • n=7 Participants
|
47.4 years
STANDARD_DEVIATION 13.0 • n=5 Participants
|
|
Sex: Female, Male
Female
|
19 Participants
n=5 Participants
|
19 Participants
n=7 Participants
|
38 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
11 Participants
n=5 Participants
|
7 Participants
n=7 Participants
|
18 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
30 participants
n=5 Participants
|
26 participants
n=7 Participants
|
56 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: One patient in the Thymoglobulin arm died on post-operative day #8, prior to undergoing a biopsy. There were other deaths in the study however there were incidences of CMR, AMR or both prior to death.
Per 2007 international Banff Classification Criteria, CMR 1A was diagnosed on biopsies displaying significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of moderate tubulitis (t2). CMR IB was diagnosed in cases with significant interstitial infiltration (\>25% of parenchyma affected, i2 or i3) and foci of severe tubulitis (t3). CMR IIA were cases with mild-to-moderate intimal arteritis (v1), while CMR IIB were those with severe intimal arteritis comprising \>25% of the luminal area (v2). CMR III were those cases with transmural arteritis and/or arterial fibrinoid change and necrosis of medial smooth muscle cells with accompanying lymphocytic inflammation (v3).
Outcome measures
| Measure |
Tymoglobulin
n=29 Participants
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 Participants
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
6-month Acute Cellular-mediated Rejection Rate (CMR)
|
14 Participants
|
20 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: One patient in the Thymoglobulin arm died on post-operative day #8, prior to undergoing a biopsy. There were other deaths in the study however there were incidences of CMR, AMR or both prior to death.
A diagnosis of AMR was based on the 2013 international Banff Classification Criteria and is defined as the presence of circulating donor-specific antibody (DSA) and either: 1) peritubular capillary staining of C4d and at least one of the following: peritubular capillaritis (ptc) score\>0, glomerulitis (g) score\>0, acute thrombotic microangiopathy (TMA) in the absence of any other cause, or other features consistent with AMR (endothelial injury, fibrin thrombi, microinfarctions, interstitial hemorrhage), or 2) absence of capillary staining of C4d and the presence of ptc\>0 and g\>0 or ptc\>0 or g\>0 and acute TMA, in the absence of any other cause of TMA.
Outcome measures
| Measure |
Tymoglobulin
n=29 Participants
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 Participants
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
6-month Acute Antibody-mediated Rejection Rate (AMR)
|
17 Participants
|
16 Participants
|
PRIMARY outcome
Timeframe: Up to 6 monthsPopulation: One patient in the Thymoglobulin arm died on post-operative day #8, prior to undergoing a biopsy. There were other deaths in the study however there were incidences of CMR, AMR or both prior to death.
Biopsy shows evidence of either AMR or CMR or evidence both.
Outcome measures
| Measure |
Tymoglobulin
n=29 Participants
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 Participants
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
6-month Cumulative Rejection Incidence (Either CMR, AMR or Both)
|
21 Participants
|
23 Participants
|
Adverse Events
Tymoglobulin
Daclizumab
Serious adverse events
| Measure |
Tymoglobulin
n=30 participants at risk
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 participants at risk
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
Surgical and medical procedures
intra-thoracic vascular injury during placement of a central venous catheter
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Renal and urinary disorders
Allograft loss
|
6.7%
2/30 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
15.4%
4/26 • Number of events 4 • One year from date of transplant
occasional assessment/testing
|
|
Gastrointestinal disorders
Perforated gastric ulcer
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Cardiac disorders
Cardiovascular disease
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
H1N1 flu
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Respiratory syncytial virus (RSV) Pneumonia
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Septic shock
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Renal and urinary disorders
Recurrent focal segmental glomerulosclerosis
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Cytomegalovirus (CMV)
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
General disorders
Fever
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Pneumonia
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Histoplasmosis
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
11.5%
3/26 • Number of events 3 • One year from date of transplant
occasional assessment/testing
|
|
General disorders
Pancreatitis
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Product Issues
Rejection
|
3.3%
1/30 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Polyoma virus (BK)
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Urinary tract infection (UTI)
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
General disorders
delirium tremens seizure
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
Other adverse events
| Measure |
Tymoglobulin
n=30 participants at risk
Thymoglobulin was administered as 1.5 mg/kg prior to reperfusion followed by 6 post-operative doses on days 1 through 6
|
Daclizumab
n=26 participants at risk
Daclizumab was administered as 2 mg/kg prior to reperfusion followed by 1 mg/kg every other week for 8 weeks post-operatively (4 post-operative doses).
|
|---|---|---|
|
Infections and infestations
Vancomycin-resistant enterococci (VRE)
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
General disorders
Fever
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
General disorders
Rash
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Wound infection
|
6.7%
2/30 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Renal and urinary disorders
Increase in creatinine
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Bile infection
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
0.00%
0/26 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Urinary Tract Infection
|
40.0%
12/30 • Number of events 17 • One year from date of transplant
occasional assessment/testing
|
34.6%
9/26 • Number of events 18 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Blood stream infection
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
11.5%
3/26 • Number of events 3 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
C-difficile infection
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
7.7%
2/26 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Cellulitis
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Central line-associated bloodstream infection (CLABSI)
|
3.3%
1/30 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
7.7%
2/26 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
|
Gastrointestinal disorders
Esophagitis
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Infection of disc space
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Intra-abdominal infection
|
16.7%
5/30 • Number of events 6 • One year from date of transplant
occasional assessment/testing
|
7.7%
2/26 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
|
Blood and lymphatic system disorders
Leukocytosis
|
0.00%
0/30 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Polyoma virus (BK)
|
6.7%
2/30 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
3.8%
1/26 • Number of events 1 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Surgical site infection
|
10.0%
3/30 • Number of events 3 • One year from date of transplant
occasional assessment/testing
|
19.2%
5/26 • Number of events 6 • One year from date of transplant
occasional assessment/testing
|
|
Infections and infestations
Upper respiratory infection (URI)
|
3.3%
1/30 • Number of events 4 • One year from date of transplant
occasional assessment/testing
|
7.7%
2/26 • Number of events 2 • One year from date of transplant
occasional assessment/testing
|
Additional Information
Robert Montgomery, MD
New York University Langone Transplant Institute
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place