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Safety and Efficacy of Desensitization Therapy in Sensitized Participants Awaiting Heart Transplantation

This study has been terminated.
(Inability to enroll within funding period)
Sponsor:
Collaborator:
Clinical Trials in Organ Transplantation
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT01769443
First received: January 14, 2013
Last updated: October 14, 2015
Last verified: October 2015
Results First Received: October 13, 2015  
Study Type: Interventional
Study Design: Allocation: Randomized;   Endpoint Classification: Safety/Efficacy Study;   Intervention Model: Parallel Assignment;   Masking: Open Label;   Primary Purpose: Treatment
Conditions: Primary Heart Transplant
Heart Transplantation
Heart Transplant
Interventions: Drug: bortezomib
Procedure: plasmapheresis

  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
The study planned to enroll 80 participants; however, the decision to terminate the study was made due to the very slow rate of participant accrual and the inability to meet the recruitment goal within the funding period. Only 2 participants were enrolled at one site before study recruitment status changed to "Active, not recruiting."

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
No Desensitization No desensitization therapy pre-transplantation
Desensitization

Plasmapheresis with concomitant bortezomib.

  • Plasmapheresis will be given for 3 consecutive days (treatment days 0, 1 and 2) within 2 weeks of Status I listing for heart transplantation. Plasmapheresis is a procedure that involves the extracorporeal separation of plasma from cellular blood components by centrifugation or membrane filtration, which removes the alloantibody. The plasma depleted blood is reconstituted with exogenous fresh-frozen plasma or albumin solution which is then infused back into the patient.
  • Four doses of bortezomib (1.3 mg/m^2) were administered intravenously on treatment days 0, 3, 7 and 10. The first dose was given between 4-8 hours after the first plasmapheresis session was completed and there was at least 96 hours between the second and third dose of bortezomib

Participant Flow:   Overall Study
    No Desensitization   Desensitization
STARTED   1   1 
COMPLETED   0   1 
NOT COMPLETED   1   0 
Study closure                1                0 



  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.
All enrolled

Reporting Groups
  Description
No Desensitization No desensitization therapy pre-transplantation
Desensitization

Plasmapheresis with concomitant bortezomib.

  • Plasmapheresis will be given for 3 consecutive days (treatment days 0, 1 and 2) within 2 weeks of Status I listing for heart transplantation. Plasmapheresis is a procedure that involves the extracorporeal separation of plasma from cellular blood components by centrifugation or membrane filtration, which removes the alloantibody. The plasma depleted blood is reconstituted with exogenous fresh-frozen plasma or albumin solution which is then infused back into the patient.
  • Four doses of bortezomib (1.3 mg/m^2) were administered intravenously on treatment days 0, 3, 7 and 10. The first dose was given between 4-8 hours after the first plasmapheresis session was completed and there was at least 96 hours between the second and third dose of bortezomib
Total Total of all reporting groups

Baseline Measures
   No Desensitization   Desensitization   Total 
Overall Participants Analyzed 
[Units: Participants]
 1   1   2 
Age 
[Units: Participants]
     
<=18 years   0   0   0 
Between 18 and 65 years   1   0   1 
>=65 years   0   1   1 
Gender 
[Units: Participants]
     
Female   1   0   1 
Male   0   1   1 
Ethnicity (NIH/OMB) 
[Units: Participants]
     
Hispanic or Latino   0   0   0 
Not Hispanic or Latino   1   1   2 
Unknown or Not Reported   0   0   0 
Race (NIH/OMB) 
[Units: Participants]
     
American Indian or Alaska Native   0   0   0 
Asian   0   0   0 
Native Hawaiian or Other Pacific Islander   0   0   0 
Black or African American   0   0   0 
White   1   1   2 
More than one race   0   0   0 
Unknown or Not Reported   0   0   0 
Region of Enrollment 
[Units: Participants]
     
United States   1   1   2 


  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Composite of Incidence of the Following Events in Subjects   [ Time Frame: At transplant, or 90 days post-randomization, whichever occurs first ]

2.  Secondary:   Time From Wait Listing to Heart Transplantation   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

3.  Secondary:   Change in Calculated PRA (cPRA) From Wait Listing to Transplantation   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

4.  Secondary:   Incidence of Death   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

5.  Secondary:   Incidence of Removal From Transplant Waiting List for Any Reason Except Improvement of Cardiac Function   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

6.  Secondary:   Incidence of Initiation of Any Mechanical Circulatory Support Device   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

7.  Secondary:   Incidence of Severe Infection Requiring Intravenous Antibiotics   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

8.  Secondary:   Incidence of Cerebral Vascular Accident   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

9.  Secondary:   Incidence of Acute Renal Failure Requiring Hemodialysis   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

10.  Secondary:   Incidence of Administering Desensitization Therapy Beyond 90 Days After Randomization   [ Time Frame: At transplant, or 1 year post-randomization, whichever occurs first ]

11.  Secondary:   Development of Angiographically Evident Cardiac Allograft Vasculopathy at 1 Year   [ Time Frame: 24 and 52 weeks post-transplantation ]

12.  Secondary:   Incidence of Serious Infections Requiring Intravenous Antimicrobial Therapy   [ Time Frame: 24 and 52 weeks post-transplantation ]

13.  Secondary:   Number of Subjects on Left Ventricular Assist Devices (LVAD) Compared to Those Not on LVADs   [ Time Frame: 24 and 52 weeks post-transplantation ]

14.  Secondary:   Cardiac Dysfunction as Reflected in the Left Ventricular Ejection Fractions < 40% by Echocardiography, Angiogram or Nuclear Testing.   [ Time Frame: 24 and 52 weeks: ]

15.  Secondary:   Incidence of Post-Transplant Lymphoproliferative Disorder (PTLD)   [ Time Frame: 24 and 52 weeks post-transplantation ]

16.  Secondary:   Death   [ Time Frame: 24 and 52 weeks post-transplantation ]

17.  Secondary:   Re-transplantation or Re-listed for Transplantation   [ Time Frame: 24 and 52 weeks post-transplantation ]

18.  Secondary:   Incidence of Hospitalizations   [ Time Frame: 24 and 52 weeks post-transplantation ]

19.  Secondary:   Incidence of Rejection Episodes Per Subject and Freedom From Rejection   [ Time Frame: 24 and 52 weeks 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
Study was terminated by the study sponsor, with agreement from the investigators. Reason: very slow rate of accrual and inability to meet the accrual goal within the funding period. (N=2 enrolled. Aim was 80 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


Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT01769443     History of Changes
Other Study ID Numbers: DAIT CTOT-13
U01AI063594 ( US NIH Grant/Contract Award Number )
Study First Received: January 14, 2013
Results First Received: October 13, 2015
Last Updated: October 14, 2015
Health Authority: United States: Food and Drug Administration