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Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation

This study has been terminated.
(Due to inability to meet accrual goals within the funding period)
Sponsor:
ClinicalTrials.gov Identifier:
NCT01278745
First Posted: January 19, 2011
Last Update Posted: April 11, 2017
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.
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Clinical Trials in Organ Transplantation
Genentech, Inc.
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
Results First Submitted: December 1, 2016  
Study Type: Interventional
Study Design: Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Prevention
Conditions: Cardiac Allograft Vasculopathy
Heart Transplant Recipients
Interventions: Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Twenty three out of N=24 participating sites in the United States enrolled 362 participants into this trial. N=163 participants reached the randomization stage of the trial.

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Rituximab Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
Placebo Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
Discontinued Pre-Transplant Subjects that enrolled, but withdrew from the study prior to their transplant.
Discontinued Pre-Randomization Subjects that were enrolled and transplanted on study, but withdrew from the study prior to randomization.

Participant Flow:   Overall Study
    Rituximab   Placebo   Discontinued Pre-Transplant   Discontinued Pre-Randomization
STARTED   89   74   121   78 
COMPLETED   84   68   0   0 
NOT COMPLETED   5   6   121   78 
Death                2                5                7                0 
Physician Decision                1                0                0                9 
Withdrawal by Subject                1                1                5                1 
Sponsor Decision                1                0                62                6 
Ineligible                0                0                42                61 
Moves,enrollment in mx studies, et al.                0                0                5                1 



  Baseline Characteristics
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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.
Randomized participants

Reporting Groups
  Description
Rituximab Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
Placebo Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
Total Total of all reporting groups

Baseline Measures
   Rituximab   Placebo   Total 
Overall Participants Analyzed 
[Units: Participants]
 89   74   163 
Age 
[Units: Years]
Mean (Standard Deviation)
 54.6  (11.80)   54.8  (11.76)   54.7  (11.75) 
Sex: Female, Male 
[Units: Participants]
Count of Participants
     
Female      16  18.0%      8  10.8%      24  14.7% 
Male      73  82.0%      66  89.2%      139  85.3% 
Ethnicity (NIH/OMB) 
[Units: Participants]
Count of Participants
     
Hispanic or Latino      9  10.1%      7   9.5%      16   9.8% 
Not Hispanic or Latino      72  80.9%      62  83.8%      134  82.2% 
Unknown or Not Reported      8   9.0%      5   6.8%      13   8.0% 
Race (NIH/OMB) 
[Units: Participants]
Count of Participants
     
American Indian or Alaska Native      0   0.0%      1   1.4%      1   0.6% 
Asian      5   5.6%      1   1.4%      6   3.7% 
Native Hawaiian or Other Pacific Islander      0   0.0%      0   0.0%      0   0.0% 
Black or African American      7   7.9%      12  16.2%      19  11.7% 
White      70  78.7%      57  77.0%      127  77.9% 
More than one race      0   0.0%      0   0.0%      0   0.0% 
Unknown or Not Reported      7   7.9%      3   4.1%      10   6.1% 
Region of Enrollment 
[Units: Participants]
Count of Participants
     
United States   89   74   163 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Change in Percent Atheroma Volume (PAV)   [ Time Frame: Baseline, 1 year ]

2.  Secondary:   Death   [ Time Frame: 12 months ]

3.  Secondary:   Re-transplantation or Re-listed for Transplantation   [ Time Frame: 6 to 12 months ]

4.  Secondary:   Number of Episodes of Biopsy Proven Acute Rejection (BPAR) of Any Grade Per Participant   [ Time Frame: 6 to 12 months ]

5.  Secondary:   Incidence of BPAR (Any Grade)   [ Time Frame: 6 to 12 months ]

6.  Secondary:   Incidence of AMR   [ Time Frame: 6 to 12 months ]

7.  Secondary:   Incidence of Cellular Rejection   [ Time Frame: 6 to 12 months ]

8.  Secondary:   Incidence of Any Treated Rejection   [ Time Frame: 6 to 12 months ]

9.  Secondary:   Number of Participants With Episodes of Rejection Associated With Hemodynamic Compromise (HDC)   [ Time Frame: 6 to 12 months ]

10.  Secondary:   Number of Participants With Development of Angiographically Evident Cardiac Allograft Vasculopathy   [ Time Frame: 1 year ]

11.  Secondary:   Number of Participants With Post-transplant Serious Infections Requiring Intravenous Antimicrobial Therapy   [ Time Frame: Transplantation through end of study, up to 1 year post transplantation. ]

12.  Secondary:   Number of Participants With Post-transplant Incidence of PTLD   [ Time Frame: Transplantation through end of study, up to 1 year post transplantation. ]

13.  Secondary:   Post-transplant Safety Outcomes Among Participants: Safety and Tolerability of Rituximab   [ Time Frame: Transplantation through end of study, up to 1 year post transplantation ]


  Serious Adverse Events


  Other Adverse Events


  Limitations and Caveats
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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 study was terminated with 163 participants randomized, well short of the study's goal of 300 randomized participants.


  More Information
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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: Director, Clinical Research Operations Program
Organization: DAIT/NIAID
phone: 301-594-7669
e-mail: DAITClinicalTrialsGov@niaid.nih.gov



Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01278745     History of Changes
Other Study ID Numbers: DAIT CTOT-11
First Submitted: January 16, 2011
First Posted: January 19, 2011
Results First Submitted: December 1, 2016
Results First Posted: April 11, 2017
Last Update Posted: April 11, 2017