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Combination Immunosuppressive Therapy to Prevent Kidney Transplant Rejection in Adults

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ClinicalTrials.gov Identifier: NCT00078559
Recruitment Status : Completed
First Posted : March 2, 2004
Results First Posted : July 9, 2012
Last Update Posted : June 29, 2018
Sponsor:
Collaborator:
Immune Tolerance Network (ITN)
Information provided by (Responsible Party):
University of Wisconsin, Madison

Study Type: Interventional
Study Design: Allocation: Non-Randomized;   Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions: Kidney Transplantation
Kidney Disease
Interventions: Drug: Alemtuzumab
Drug: Sirolimus
Drug: Tacrolimus
Procedure: Kidney transplant
Drug: Methylprednisolone (or equivalent)
Drug: Acetaminophen
Drug: Diphenhydramine
Drug: Trimethoprim (TMP)/Sulfa (Bactrim, Septra)
Drug: Valgancyclovir
Drug: Acyclovir
Drug: Pentamidine
Drug: Clotrimazole
Drug: Nystatin

  Participant Flow

Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
For this trial, one center in the United States enrolled ten eligible adult recipients of first kidney transplants (0-3 human leukocyte antigen (HLA)-antigen mismatch) from February 2005 to February 2006

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
At a screening visit, participants underwent procedures to establish inclusion/exclusion criteria and then sign the informed consent form. Refer to inclusion and exclusion criteria section for more details

Reporting Groups
  Description
Alemtuzumab Recipients of first kidney transplants (0-3 HLA antigen mismatch) received induction therapy with alemtuzumab (1 dose [30 mg]each day, Days 0 [transplant day], 1 and 2, administered intravenously) , tacrolimus (the dose was initially 2 mg twice daily by mouth, and adjusted to maintain target blood levels of 4 to 8 ng/mL from Day 1 to Day 60) and sirolimus (the initial dose was 2 mg/day by mouth started <= 48 hours post-transplant, subsequently adjusted to achieve trough levels of 8 to 12 ng/mL through Month 12), followed by sirolimus withdrawal as tolerated

Participant Flow:   Overall Study
    Alemtuzumab
STARTED   10 
COMPLETED   10 [1] 
NOT COMPLETED   0 
[1] 1 subject stopped study drug due to a severe but non-serious AE, and completed the trial



  Baseline Characteristics

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
No text entered.

Reporting Groups
  Description
Alemtuzumab Recipients of first kidney transplants (0-3 HLA antigen mismatch) received induction therapy with alemtuzumab (1 dose [30 mg]each day, Days 0 [transplant day], 1 and 2, administered intravenously) , tacrolimus (the dose was initially 2 mg twice daily by mouth, and adjusted to maintain target blood levels of 4 to 8 ng/mL from Day 1 to Day 60) and sirolimus (the initial dose was 2 mg/day by mouth started <= 48 hours post-transplant, subsequently adjusted to achieve trough levels of 8 to 12 ng/mL through Month 12), followed by sirolimus withdrawal as tolerated

Baseline Measures
   Alemtuzumab 
Overall Participants Analyzed 
[Units: Participants]
 10 
Age 
[Units: Participants]
Count of Participants
 
<=18 years      0   0.0% 
Between 18 and 65 years      10 100.0% 
>=65 years      0   0.0% 
Age 
[Units: Years]
Mean (Standard Deviation)
 45.3  (10.5) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
 
Female      3  30.0% 
Male      7  70.0% 
Region of Enrollment 
[Units: Participants]
 
United States   10 
Primary Cause of Renal Failure 
[Units: Participants]
 
Glomerulonephritis   0 
Pyelonephritis/Interstitial Nephritis   0 
Cystic/Polycystic Kidney Disease   4 
Hypertension   0 
Diabetes Mellitus   1 
Obstructive/Reflux Nephropathy   1 
IgA Nephropathy   2 
Post-streptococcal Glomerular Nephritis   0 
Systemic Lupus Erythematosus   0 
Etiology Uncertain   2 
Other   0 
Pre-Transplant Dialysis [1] 
[Units: Participants]
 
Hemodialysis and Peritoneal Dialysis   0 
Hemodialysis   5 
Peritoneal Dialysis   0 
Dialysis - Unknown Type   0 
Participants without pre-transplant dialysis   5 
[1] Whether or not participant received dialysis pre-transplant and if they did, the type they received.


  Outcome Measures

1.  Primary:   Number of Acute Rejections in All Enrolled Participants   [ Time Frame: Four years post-transplant ]

2.  Secondary:   Number of Acute Rejections in All Enrolled Participants Following Sirolimus Withdrawal   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]

3.  Secondary:   Number of Acute Rejections Between Initiation of Sirolimus Withdrawal and End of Study   [ Time Frame: Initiation of sirolimus to end of study (up to four years post-transplant) ]

4.  Secondary:   Time From Transplantation to Acute Rejection in Participants for Whom Sirolimus Withdrawal Was Not Initiated   [ Time Frame: Transplantation to acute rejection (up to four years post-transplantation) ]

5.  Secondary:   Time From Transplantation to Acute Rejection in Participants for Whom Acute Rejection Occurred During the 1 Year Post-transplant Period   [ Time Frame: Transplantation to acute rejection (up to one year post-transplant) ]

6.  Secondary:   Number of Deaths Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to Death (up to four years post-transplant) ]

7.  Secondary:   Number of Participants Who Experienced Graft Loss Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to Graft Loss (up to four years post-transplantation) ]

8.  Secondary:   Number of Severe Acute Rejections Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to severe acute rejection (up to four years post-transplantation) ]

9.  Secondary:   Number of Participants Requiring Anti-lymphocyte Therapy for an Acute Rejection, Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to acute rejection (up to four years post-transplantation) ]

10.  Secondary:   Number of Alemtuzumab Associated Adverse Events, Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]

11.  Secondary:   Number of Tacrolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]

12.  Secondary:   Number of Sirolimus Associated Adverse Events, Stratified by Sirolimus Withdrawal Status   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]

13.  Secondary:   Number of Side Effects of Conventional Immunosuppression, Stratified by Withdrawal Status   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]

14.  Secondary:   Change in Renal Function as Measured by Serum Creatinine, Stratified by Withdrawal Status   [ Time Frame: Transplantation to end of study (up to four years post-transplant) ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats

Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
The absence of a control group in this pilot trial precludes any comparison between alemtuzumab-induced patients with further minimization and patients with more conventional immunosuppressive approaches, and is a limitation of the current study


  More Information

Certain Agreements:  
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.


Results Point of Contact:  
Name/Title: Arjang Djamali, MD, MS, FASN
Organization: University of Wisconsin - Department of Medicine, Madison, Wisconsin
phone: 608-262-7330
e-mail: axd@medicine.wisc.edu


Publications:

Responsible Party: University of Wisconsin, Madison
ClinicalTrials.gov Identifier: NCT00078559     History of Changes
Obsolete Identifiers: NCT00585130
Other Study ID Numbers: DAIT ITN013ST
H-2003-0435 ( Other Identifier: HS IRB )
First Submitted: March 1, 2004
First Posted: March 2, 2004
Results First Submitted: April 13, 2012
Results First Posted: July 9, 2012
Last Update Posted: June 29, 2018