Alloantibodies in Pediatric Heart Transplantation | NCT01005316

ID	Type	Description	Link
7U01AI077867-02	U.S. NIH Grant/Contract		View source

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH

Description Module

Detailed Description

There is currently a renewed interest in alloantibodies in transplantation. In 1966, Kissmeyer and colleagues reported that pre-existing antibodies directed against donor cells could cause hyperacute rejection of the renal allograft. Three years later, in a landmark study, Patel and Terasaki showed that a lymphocytotoxic assay to identify donor-specific antibodies was highly predictive of acute graft failure. These observations led to the practice of performing prospective, donor-specific crossmatches by lymphocytotoxicity assay for all kidney transplants and for heart and lung transplants when the candidate has a positive panel reactive antibody (PRA) assay. A concept evolved that transplantations should not be performed across a positive cytotoxicity crossmatch. The purpose of this study is to determine the clinical outcomes of sensitized pediatric heart transplant recipients with a positive donor-specific cytotoxicity crossmatch and to compare this group with outcomes in nonsensitized heart transplant recipients.

This study plans to enroll 370 pediatric heart transplant recipients over a period of 3 years. The follow-up period will last up to 3 years. All participants will be enrolled pretransplant. In the pretransplant phase, visits will occur every 6 months. These routine visits will continue until transplant or the end of the study. They will coincide with routine pretransplant status visits. At the time of transplant, the participants will be assigned to one of two groups. Group A will include participants who are allo-antibody negative (less than 10% by AHG CDC-PRA and ELISA in all DTT-treated serum samples). Cohort B will include participants who have the presence of a DTT-treated AHG CDC-PRA of greater than or equal to 10% and/or an ELISA-PRA greater than or equal to 10% in any pretransplant sample.

Both cohorts will receive standard transplantation care. This study has no interventions. All participants will undergo regular blood tests, and, those in the sensitized group will have additional blood testing performed after the transplant and lasting until the end of the study. Post-transplant visits will occur while participants are recovering in the hospital; at Months 1, 3, and 6; and annually until the study closes.

The information collected for the study include data from a physical exam, routine testing, adverse (AEs) and serious adverse (SAEs) events assessments, and blood collection. Each time a biopsy is done, the study will ask to review the biopsy tissue and to collect a sample. If stored tissue is not available, none will be collected.

Label	Type	Description	Intervention Names
Cohort A: Non-Sensitized		Cohort A will include participants who are alloantibody Luminex(TM) LABScreen. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Non-sensitized recipients receive steroid-free maintenance immunosuppression: Induction Therapy (anti-T cell antibody induction) Tacrolimus (Prograf®) Mycophenolate Mofetil- MMF (CellCept®).	Drug: Induction Therapy Drug: Tacrolimus Drug: Mycophenolate Mofetil
Cohort B: Sensitized		Cohort B will include participants who are alloantibody positive (Sensitized) as determined by Luminex LabScreen for Class I or Class II with specificities identified by single antigen testing. There is no study mandated care or treatment. All care given is clinical site standard of care. All sites follow a similar standard of care regimen. Sensitized recipients receive: 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®) Mycophenolate Mofetil-MMF (CellCept®).	Drug: Induction Therapy Drug: Tacrolimus Drug: Mycophenolate Mofetil Procedure: Intraoperative plasma exchange/pheresis Procedure: Short-term post-operative plasmapheresis Drug: Immunoglobulins, Intravenous Drug: Prednisone

Name	Type	Description	Arm Group Labels	Other Names
Induction Therapy	Drug	Per standard of care guidelines for immunosuppression at each clinical site.	Cohort A: Non-Sensitized Cohort B: Sensitized

Measure	Description	Time Frame
Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation	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.	12 months post-transplantation

Measure	Description	Time Frame
Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies	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.

Name	Affiliation	Role
Stephen A. Webber, MBChB, MRCP	University of Pittsburgh	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Children's Hospital Boston, Harvard Medical School		Boston	Massachusetts	02115	United States
St. Louis Children's Hospital, Washington University

PubMed Identifier	Type	Citation	Retractions
19375471	Background	Rose ML, Smith JD. Clinical relevance of complement-fixing antibodies in cardiac transplantation. Hum Immunol. 2009 Aug;70(8):605-9. doi: 10.1016/j.humimm.2009.04.016. Epub 2009 Apr 16.
4886455	Background	Patel R, Terasaki PI. Significance of the positive crossmatch test in kidney transplantation. N Engl J Med. 1969 Apr 3;280(14):735-9. doi: 10.1056/NEJM196904032801401. No abstract available.

Label	URL
National Institute of Allergy and Infectious Diseases (NIAID) website	View source

ID	Title	Description
FG000	Enrolled, Not Transplanted	These participants were consented and enrolled into the study, but did not receive a heart transplant as specified by the protocol.
FG001	Cohort A: Non-Sensitized

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Percentage of Participants Positive for Event of Death, Graft Loss or Rejection With Hemodynamic Compromise at 12 Months Post-Transplantation

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.

Transplanted Participants

Posted

Number

percentage of participants

12 months post-transplantation

ID	Title	Description
OG000	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)).
OG001	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)).
OG002	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)).

Units	Counts
Participants	OG00097 OG00116 OG002127

Title

Denominators

Categories

Title	Measurements
	OG0005.2 OG00112.5 OG00211.8

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000 OG001 OG002	The p-value compares Cohort A: Non-Sensitized with Cohort B: Sensitized, Crossmatch Positive.	Fisher Exact		0.2580														Superiority or Other

Secondary

Time to Production of Post-Transplant de Novo Donor-specific Alloantibodies

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.

Transplanted Participants

Posted

Mean

Full Range

Days

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants Positive for de Novo Donor-Specific Alloantibody Production in the First Year Post-Transplantation

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.

Transplanted Participants

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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),
OG001	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)).

Secondary

Percentage of Participants- Mortality While on Transplantation Wait-List

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

Participants Enrolled, Not Transplanted

Posted

Number

percentage of participants

Pre-transplantation

ID	Title	Description
OG000	Enrolled, Not Transplanted	These participants were consented and enrolled into the study, but did not receive a heart transplant as specified by the protocol.

Units	Counts
Participants	OG00051

Secondary

Time From Participant Listing on Organ Wait-List to Receiving Organ Transplant, Death or De-Listing

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.

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

Posted

Mean

Full Range

Days

Study enrollment to transplantation

ID	Title	Description
OG000	Enrolled	Enrolled participants who died, were transplanted or de-listed.

Units	Counts
Participants	OG000

Secondary

Percentage of Participants With the Presence of Anti-HLA IgG Antibodies by Luminex SA Testing

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

Transplanted Participants

Posted

Number

percentage of participants

Pre-transplantation

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants -Quantification of Anti-HLA IgG Antibodies by Luminex SA Testing

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

Transplanted Participants

Posted

Number

percentage of participants

Pre-transplantation

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants With the Presence of Anti-MICA Antibodies by Luminex TM Assay

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.

Transplanted Participants

Posted

Number

percentage of participants

Pre-Transplantation

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants -Overall Participant and Graft Survival

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

Transplanted Participants

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Presence of C4d on Endomyocardial Biopsy (EMB)

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

Transplanted Participants

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants With Occurrence of Re-Hospitalization(s)

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

Transplanted Participants

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants Positive for Severe Infection(s)

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

Transplanted Participants

Posted

Number

percentage of participants

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Time to Diagnosis of Chronic Rejection

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.

Transplanted Participants

Posted

Mean

Full Range

Days

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Time to Post-Transplantation Lymphoproliferative Disorder

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.

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).

Posted

Mean

Full Range

Days

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Time to New-Onset Diabetes Mellitus

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.

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).

Posted

Mean

Full Range

Days

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

ID	Title	Description
OG000	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)).
OG001	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)).

Secondary

Percentage of Participants Experiencing 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).

Transplanted Participants

Posted

Number

percentage of participants

Transplantation to the end of study.

ID	Title	Description
OG000	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)).
OG001	Cohort B: Sensitized, Crossmatch Positive

Secondary

Time to Acute Rejection

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.

Transplanted Participants

Posted

Mean

Full Range

Days

Transplantation to the end of study.

ID	Title	Description
OG000	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)).
OG001

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Neutropenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pancytopenia	Blood and lymphatic system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Atrial tachycardia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Atrioventricular block complete	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Bradycardia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Cardiac arrest	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Cardiac failure	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Cardiac failure high output	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Myocardial reperfusion injury	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pericardial effusion	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0002 events2 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Right ventricular dysfunction	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Right ventricular failure	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Tachycardia	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Torsade de pointes	Cardiac disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Ascites	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Diarrhoea	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Gastric polyps	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Gastrointestinal haemorrhage	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Vomiting	Gastrointestinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0023 events3 affected127 at risk
Fatigue	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Multi-organ failure	General disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pyrexia	General disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0023 events3 affected127 at risk
Cholecystitis	Hepatobiliary disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Serum sickness	Immune system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Transplant rejection	Immune system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0012 events2 affected16 at risk EG0026 events5 affected127 at risk
Bacteraemia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0023 events2 affected127 at risk
Bronchiolitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Clostridial infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Cytomegalovirus colitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Cytomegalovirus infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Cytomegalovirus viraemia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Device related infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Enteritis infectious	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Epstein-Barr virus infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Fungal endocarditis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Gastroenteritis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0004 events4 affected97 at risk EG0010 events0 affected16 at risk EG0023 events3 affected127 at risk
Gastroenteritis viral	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Gastrointestinal infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Influenza	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Neutropenic infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Otitis media acute	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pneumonia	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0004 events4 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Pneumonia viral	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Respiratory syncytial virus bronchiolitis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Respiratory syncytial virus infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Sepsis	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Septic shock	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Upper respiratory tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Urinary tract infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0011 events1 affected16 at risk EG0021 events1 affected127 at risk
Viral infection	Infections and infestations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Graft dysfunction	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Post procedural haemorrhage	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Tracheostomy malfunction	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Transplant failure	Injury, poisoning and procedural complications	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0011 events1 affected16 at risk EG0022 events2 affected127 at risk
Hepatic enzyme increased	Investigations	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Oxygen saturation decreased	Investigations	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Dehydration	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Diabetes mellitus	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Electrolyte imbalance	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Hypophagia	Metabolism and nutrition disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Synovitis	Musculoskeletal and connective tissue disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Epstein-Barr virus associated lymphoproliferative disorder	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0023 events3 affected127 at risk
Cerebral haemorrhage	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Cerebral ischaemia	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Posterior reversible encephalopathy syndrome	Nervous system disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Delirium	Psychiatric disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Renal failure acute	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0012 events2 affected16 at risk EG0020 events0 affected127 at risk
Renal impairment	Renal and urinary disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Laryngeal stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Pulmonary haemorrhage	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0011 events1 affected16 at risk EG0020 events0 affected127 at risk
Pulmonary vein stenosis	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0022 events2 affected127 at risk
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0011 events1 affected16 at risk EG0021 events1 affected127 at risk
Arterial thrombosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Haemorrhage	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Hypertension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0020 events0 affected127 at risk
Hypotension	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0001 events1 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk
Venous thrombosis	Vascular disorders	MedDRA 14.0	Systematic Assessment	EG0000 events0 affected97 at risk EG0010 events0 affected16 at risk EG0021 events1 affected127 at risk

ID	Term
D020360	Neoadjuvant Therapy
D016559	Tacrolimus
D009173	Mycophenolic Acid
D001781	Blood Component Removal
D010956	Plasmapheresis
D016756	Immunoglobulins, Intravenous
D011241	Prednisone
D000305	Adrenal Cortex Hormones

ID	Term
D003131	Combined Modality Therapy
D013812	Therapeutics
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals
D002208	Caproates
D000144	Acids, Acyclic
D002264	Carboxylic Acids
D005227	Fatty Acids
D008055	Lipids
D016060	Sorption Detoxification
D005112	Extracorporeal Circulation
D013514	Surgical Procedures, Operative
D007074	Immunoglobulin G
D007132	Immunoglobulin Isotypes
D000906	Antibodies
D007136	Immunoglobulins
D007162	Immunoproteins
D001798	Blood Proteins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D012712	Serum Globulins
D005916	Globulins
D011244	Pregnadienediols
D011245	Pregnadienes
D011278	Pregnanes
D013256	Steroids
D000072473	Fused-Ring Compounds
D011083	Polycyclic Compounds
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists

ID	Title	Description
BG000	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)).
BG001	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)).
BG002	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)).
BG003	Total	Total of all reporting groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)
EG000	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)).	5	97	30	97
EG001	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))	1	16	7	16
EG002	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)).	16	127	43	127