Trial Outcomes & Findings for Alloantibodies in Pediatric Heart Transplantation (NCT NCT01005316)

NCT ID: NCT01005316

Last Updated: 2017-04-20

Results Overview

This is a composite outcome of death, graft loss or rejection with hemodynamic compromise. Rejection was considered to be with hemodynamic compromise if the rejection event had new onset echocardiographically measured from fractional shortening \<26% with ≥5% fall from last echocardiogram or the rejection event had new onset of heart failure.

• Recruitment status: TERMINATED
• Target enrollment: 290 participants
• Primary outcome timeframe: 12 months post-transplantation
• Results posted on: 2017-04-20

Participant Flow

Participant milestones

Measure	Enrolled, Not Transplanted These participants were consented and enrolled into the study, but did not receive a heart transplant as specified by the protocol.	Cohort A: Non-Sensitized Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Overall Study STARTED	50	97	16	127
Overall Study COMPLETED	0	21	5	19
Overall Study NOT COMPLETED	50	76	11	108

Reasons for withdrawal

Measure	Enrolled, Not Transplanted These participants were consented and enrolled into the study, but did not receive a heart transplant as specified by the protocol.	Cohort A: Non-Sensitized Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Overall Study Adverse Event	0	0	0	1
Overall Study Death	20	5	1	15
Overall Study Study Termination	5	63	9	85
Overall Study Lost to Follow-up	1	3	0	2
Overall Study Physician Decision	6	0	0	0
Overall Study Sponsor Decision	6	3	0	0
Overall Study Withdrawal by Subject	1	1	0	2
Overall Study Consented to Another Study	2	0	0	0
Overall Study Delisted	8	0	0	0
Overall Study Transferred Care	1	0	1	3
Overall Study Retransplanted	0	1	0	0

Baseline Characteristics

Alloantibodies in Pediatric Heart Transplantation

Baseline characteristics by cohort

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Total n=240 Participants Total of all reporting groups
Age, Categorical <=18 years	93 Participants n=5 Participants	16 Participants n=7 Participants	124 Participants n=5 Participants	233 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	4 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	6.9 years STANDARD_DEVIATION 6.8 • n=5 Participants	7.8 years STANDARD_DEVIATION 6.7 • n=7 Participants	7.4 years STANDARD_DEVIATION 6.3 • n=5 Participants	7.2 years STANDARD_DEVIATION 6.5 • n=4 Participants
Sex: Female, Male Female	53 Participants n=5 Participants	5 Participants n=7 Participants	54 Participants n=5 Participants	112 Participants n=4 Participants
Sex: Female, Male Male	44 Participants n=5 Participants	11 Participants n=7 Participants	73 Participants n=5 Participants	128 Participants n=4 Participants
Region of Enrollment Canada	12 participants n=5 Participants	1 participants n=7 Participants	18 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment United States	85 participants n=5 Participants	15 participants n=7 Participants	109 participants n=5 Participants	209 participants n=4 Participants

PRIMARY outcome

Timeframe: 12 months post-transplantation

Population: Transplanted Participants

This is a composite outcome of death, graft loss or rejection with hemodynamic compromise.

Rejection was considered to be with hemodynamic compromise if the rejection event had new onset echocardiographically measured from fractional shortening <26% with ≥5% fall from last echocardiogram or the rejection event had new onset of heart failure.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation	5.2 percentage of participants	12.5 percentage of participants	11.8 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to first year post transplant (up to 12 months post transplant).

Population: Transplanted Participants

Time (in days) from transplant to development of de novo donor-specific alloantibodies (DSA). This measure is calculated as time from transplant until the earliest time of development of any de novo DSA. The DSA is a newly developed alloantibody that is against the donor organ. Alloantibodies are important mediators of acute and chronic rejection.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies	28.1 Days Interval 6.0 to 242.0	15.4 Days Interval 6.0 to 69.0	55.1 Days Interval 7.0 to 355.0

SECONDARY outcome

Timeframe: Transplantation to first year post transplant (up to 12 months post transplant).

Population: Transplanted Participants

A de novo donor-specific alloantibody (DSA) is a newly developed alloantibody that is against the donor organ. This measure includes all de novo DSA (≥1000 MFI) regardless of is persistence or timing within the first year post-transplant. Alloantibodies are important mediators of acute and chronic rejection.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants Positive for de Novo Donor-Specific Alloantibody Production in the First Year Post-Transplantation	22.7 percentage of participants	50.0 percentage of participants	37.8 percentage of participants

SECONDARY outcome

Timeframe: Pre-transplantation

Population: Participants Enrolled, Not Transplanted

Death that occurred while on the transplantation wait-list, and thus before receiving a heart transplant.

Outcome measures

Measure	Cohort A: Non-Sensitized n=51 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants- Mortality While on Transplantation Wait-List	39.2 percentage of participants	—	—

SECONDARY outcome

Timeframe: Study enrollment to transplantation

Population: Enrolled participants who died, were transplanted or de-listed.

Time (in days) from listing on the organ wait-list to receiving an organ transplant, death or de-listing. This measure is calculated as time from listing on the organ wait-list until the earliest time among transplantation, death and de-listing.

Outcome measures

Measure	Cohort A: Non-Sensitized n=279 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time From Participant Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing	128.3 Days Interval 0.0 to 1474.0	—	—

SECONDARY outcome

Timeframe: Pre-transplantation

Population: Transplanted Participants

Luminex SA testing was used to detect the presence of anti-HLA IgG Antibodies for all samples at a central laboratory.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants With the Presence of Anti-HLA IgG Antibodies by Luminex SA Testing	22.7 percentage of participants	81.3 percentage of participants	68.5 percentage of participants

SECONDARY outcome

Timeframe: Pre-transplantation

Population: Transplanted Participants

Quantification of anti-HLA IgG antibodies is measured in mean fluorescence intensity (MFI). The maximum MFI for the given subject is provided.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing Missing	0 percentage of participants	0 percentage of participants	2.4 percentage of participants
Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing None	77.3 percentage of participants	18.8 percentage of participants	29.1 percentage of participants
Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing MFI 1000-3999	20.6 percentage of participants	6.3 percentage of participants	29.9 percentage of participants
Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing MFI 4000-7999	1.0 percentage of participants	12.5 percentage of participants	14.2 percentage of participants
Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing MFI ≥8000	1.0 percentage of participants	62.5 percentage of participants	24.4 percentage of participants

SECONDARY outcome

Timeframe: Pre-Transplantation

Population: Transplanted Participants

Major histocompatibility complex class I chain-related gene A (MICA) is an antigen that is a potential marker of rejection. Luminex TM assay was used to detect its presence.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants With the Presence of Anti-MICA Antibodies by Luminex TM Assay	8.2 percentage of participants	18.8 percentage of participants	11.0 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants

This measure looks at the participants who did not die and/or did not receive a subsequent heart transplant.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants -Overall Participant and Graft Survival	93.8 percentage of participants	93.8 percentage of participants	87.4 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants

The biopsy of the heart stained positive for the presence of C4d, a potential marker of rejection.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Presence of C4d on Endomyocardial Biopsy (EMB)	18.6 percentage of participants	62.5 percentage of participants	34.6 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants

Hospitalization is defined as any hospitalization lasting greater than 24 hours.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants With Occurrence of Re-Hospitalization(s)	66.0 percentage of participants	75.0 percentage of participants	62.2 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants

Severe infections are defined as a clinical illness considered likely infectious in origin that leads to hospitalization.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants Positive for Severe Infection(s)	34.0 percentage of participants	43.8 percentage of participants	30.7 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants

Time (in days) to the diagnosis of chronic rejection. Chronic rejection is defined as stenosis, irregularity, or ectasia of the epicardial vessels, or severe peripheral pruning of the distal coronary artery tree. Time to diagnosis is time from transplantation until the first diagnosis of chronic rejection.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time to Diagnosis of Chronic Rejection	606.8 Days Interval 264.0 to 1079.0	NA Days No participants in this group were diagnosed with chronic rejection	398.9 Days Interval 4.0 to 1096.0

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants. Note to provide relevant outcome measure perspective- Of the overall number of participants analyzed, the number of diagnosed PTLD cases within groups were: Cohort A: Non-Sensitized (N=1); Cohort B: Sensitized, Crossmatch Positive (N=0); and Cohort B: Sensitized, Crossmatch Negative (N=3).

Time (in days) post-transplant lymphoproliferative disorder (PTLD). PTLD is defined as histopathological evidence of lymphoid proliferation (nodal or extranodal) fulfilling the criteria of the revised classification of the WHO 2008 (Swerdlow 2008). Time to PTLD is time from transplantation until the diagnosis of PTLD.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time to Post-Transplantation Lymphoproliferative Disorder	910 Days Interval 910.0 to 910.0	NA Days No participants in this group were diagnosed with PTLD	118.7 Days Interval 92.0 to 151.0

SECONDARY outcome

Timeframe: Transplantation to the end of study (up to 4 years post transplant).

Population: Transplanted Participants. Note to provide relevant outcome measure perspective -Of the overall number of participants analyzed, the number of new onset diabetes mellitus cases diagnosed within groups were: Cohort A: Non-Sensitized (N=1); Cohort B: Sensitized, Crossmatch Positive (N=2); and Cohort B: Sensitized, Crossmatch Negative (N=7).

Time (in days) to new-onset diabetes mellitus. New-onset diabetes mellitus is defined as the new onset of insulin dependency or the need for oral hypoglycemic agents lasting more than 30 days post-transplant. Time to new-onset diabetes is time from transplantation until the diagnosis of new-onset diabetes.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time to New-Onset Diabetes Mellitus	73 Days Interval 73.0 to 73.0	48 Days Interval 20.0 to 76.0	283.4 Days Interval 5.0 to 965.0

SECONDARY outcome

Timeframe: Transplantation to the end of study.

Population: Transplanted Participants

Acute rejection is defined as any one of the following types of rejection: acute cellular rejection (International Society for Heart and Lung Transplant (ISHLT)) system for grading rejection grade 2R or greater), acute refractory cellular rejection (acute cellular rejection unresponsive to two sequential courses of corticosteroids), acute antibody mediated rejection (histological evidence of unequivocal acute capillary injury, with complement deposition and margination of macrophages with or without neutrophils), acute mixed rejection (evidence of acute antibody mediated rejection with ISHLT grade 1R or greater), or acute clinical rejection (clinically-based acute rejection, no matter the ISHLT grade, leading to an acute augmentation of immunosuppression).

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Percentage of Participants Experiencing Acute Rejection	27.8 percentage of participants	75.0 percentage of participants	49.6 percentage of participants

SECONDARY outcome

Timeframe: Transplantation to the end of study.

Population: Transplanted Participants

Time (in days) to acute rejection. Acute rejection is defined as any one of the following types of rejection: acute cellular rejection (International Society for Heart and Lung Transplant (ISHLT) system for grading rejection grade 2R or greater), acute refractory cellular rejection (acute cellular rejection unresponsive to two sequential courses of corticosteroids), acute antibody mediated rejection (histological evidence of unequivocal acute capillary injury, with complement deposition and margination of macrophages with or without neutrophils), acute mixed rejection (evidence of acute antibody mediated rejection with ISHLT grade 1R or greater), or acute clinical rejection (clinically-based acute rejection, no matter the ISHLT grade, leading to an acute augmentation of immunosuppression). Time to acute rejection is time from transplantation to first acute rejection date.

Outcome measures

Measure	Cohort A: Non-Sensitized n=97 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Negative n=127 Participants Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Time to Acute Rejection	151.0 Days Interval 8.0 to 991.0	74.5 Days Interval 6.0 to 608.0	124.7 Days Interval 4.0 to 933.0

Adverse Events

Cohort A: Non-Sensitized

Serious events: 30 serious events

Other events: 0 other events

Deaths: 5 deaths

Cohort B: Sensitized, Crossmatch Positive

Serious events: 7 serious events

Other events: 0 other events

Deaths: 1 deaths

Cohort B: Sensitized, Crossmatch Negative

Serious events: 43 serious events

Other events: 0 other events

Deaths: 16 deaths

Serious adverse events

Measure	Cohort A: Non-Sensitized n=97 participants at risk Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody negative as determined by Luminex(TM) LABScreen. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Non-sensitized recipients received steroid-free maintenance immunosuppression: induction therapy (anti-T cell antibody induction), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).	Cohort B: Sensitized, Crossmatch Positive n=16 participants at risk Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch positivity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, a post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R))	Cohort B: Sensitized, Crossmatch Negative n=127 participants at risk Participants were enrolled into the study and received a heart transplant. Immediately prior to transplant, these participants were alloantibody positive as determined by Luminex(TM) LabScreen for Class I or Class II with specificities identified by single antigen testing. Retrospective cytotoxicity donor-specific crossmatch during their transplant procedure indicated crossmatch negativity. All administered care was clinical site standard of care. All sites followed a similar standard of care regimen. Sensitized recipients received: induction therapy (anti-T cell antibody induction), intraoperative plasma exchange/-pheresis, short-term post-operative plasmapheresis, post-transplant course of intravenous immunoglobulin (IVIG) therapy, maintenance corticosteroids (Prednisone), tacrolimus (Prograf(R)), and Mycophenolate Mofetil- MMF (CellCept(R)).
Blood and lymphatic system disorders Anaemia	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Blood and lymphatic system disorders Febrile neutropenia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Blood and lymphatic system disorders Neutropenia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Blood and lymphatic system disorders Pancytopenia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Atrial tachycardia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Atrioventricular block complete	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Bradycardia	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Cardiac arrest	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Cardiac failure	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Cardiac failure high output	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Myocardial reperfusion injury	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Pericardial effusion	2.1% 2/97 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Right ventricular dysfunction	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Right ventricular failure	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Tachycardia	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Cardiac disorders Torsade de pointes	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Gastrointestinal disorders Ascites	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Gastrointestinal disorders Diarrhoea	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Gastrointestinal disorders Gastric polyps	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Gastrointestinal disorders Vomiting	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	2.4% 3/127 • Number of events 3 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
General disorders Fatigue	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
General disorders Multi-organ failure	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
General disorders Pyrexia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	2.4% 3/127 • Number of events 3 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Hepatobiliary disorders Cholecystitis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Immune system disorders Serum sickness	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Immune system disorders Transplant rejection	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	12.5% 2/16 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	3.9% 5/127 • Number of events 6 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Bacteraemia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 3 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Bronchiolitis	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Clostridial infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Cytomegalovirus colitis	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Cytomegalovirus infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Cytomegalovirus viraemia	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Device related infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Enteritis infectious	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Epstein-Barr virus infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Fungal endocarditis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Gastroenteritis	4.1% 4/97 • Number of events 4 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	2.4% 3/127 • Number of events 3 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Gastroenteritis viral	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Gastrointestinal infection	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Influenza	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Neutropenic infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Otitis media acute	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Pneumonia	4.1% 4/97 • Number of events 4 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Pneumonia viral	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Respiratory syncytial virus bronchiolitis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Respiratory syncytial virus infection	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Sepsis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Septic shock	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Upper respiratory tract infection	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Urinary tract infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Infections and infestations Viral infection	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Injury, poisoning and procedural complications Graft dysfunction	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Injury, poisoning and procedural complications Post procedural haemorrhage	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Injury, poisoning and procedural complications Tracheostomy malfunction	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Injury, poisoning and procedural complications Transplant failure	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Investigations Hepatic enzyme increased	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Investigations Oxygen saturation decreased	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Metabolism and nutrition disorders Dehydration	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Metabolism and nutrition disorders Diabetes mellitus	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Metabolism and nutrition disorders Electrolyte imbalance	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Metabolism and nutrition disorders Hyperglycaemia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Metabolism and nutrition disorders Hypophagia	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Musculoskeletal and connective tissue disorders Synovitis	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Epstein-Barr virus associated lymphoproliferative disorder	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	2.4% 3/127 • Number of events 3 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Nervous system disorders Cerebral haemorrhage	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Nervous system disorders Cerebral ischaemia	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Nervous system disorders Posterior reversible encephalopathy syndrome	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Psychiatric disorders Delirium	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Renal and urinary disorders Renal failure acute	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	12.5% 2/16 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Renal and urinary disorders Renal impairment	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Respiratory, thoracic and mediastinal disorders Laryngeal stenosis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Respiratory, thoracic and mediastinal disorders Pleural effusion	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary haemorrhage	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Respiratory, thoracic and mediastinal disorders Pulmonary vein stenosis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	1.6% 2/127 • Number of events 2 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Respiratory, thoracic and mediastinal disorders Respiratory distress	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	6.2% 1/16 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Vascular disorders Arterial thrombosis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Vascular disorders Haemorrhage	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Vascular disorders Hypertension	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/127 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Vascular disorders Hypotension	1.0% 1/97 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.
Vascular disorders Venous thrombosis	0.00% 0/97 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.00% 0/16 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.	0.79% 1/127 • Number of events 1 • Transplantation through end of study (up to 3 years) Only serious adverse events were collected.

Other adverse events

Adverse event data not reported

Additional Information

Director, Clinical Research Operations Program

DAIT/NIAID

Phone: 301-594-7669

Email: DAITClinicalTrialsGov@niaid.nih.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place