Prevention of Cardiac Allograft Vasculopathy Using Rituxi... | NCT01278745

NCT01278745

Status Module

Sponsor/Collaborators Module

Name	Class
National Heart, Lung, and Blood Institute (NHLBI)	NIH
Clinical Trials in Organ Transplantation	NETWORK
Genentech, Inc.	INDUSTRY
Rho Federal Systems Division, Inc.

Oversight Module

Description Module

Conditions Module

Design Module

Interventional Study Design

Biospecimen

No data available

No data is available for this block.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Rituximab	Experimental	Rituximab induction/conventional immunosuppression	Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Rituximab Placebo	Placebo Comparator	Rituximab Placebo / conventional immunosuppression	Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)	Biological		Rituximab
Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change in Percent Atheroma Volume (PAV)	Nominal or noticeable change, bad or good, from baseline to 1 year in percent atheroma volume (PAV) which is a measure of the degree of coronary arterial obstruction due to host alloimmune processes measured by intravascular ultrasound (IVUS) in a target coronary artery. Thus a decrease in PAV would be an indicator of less obstruction and a better outcome.	Baseline, 1 year

Secondary Outcomes

Measure	Description	Time Frame
Death	Participants who died within 12 months post-transplant	12 months
Re-transplantation or Re-listed for Transplantation	Re-transplantation is defined as the receipt of a subsequent heart transplant and re-listed for transplantation is being listed back on the heart transplant list to be re-transplanted.

Eligibility Module

Eligibility Criteria

Inclusion Criteria for Initial Enrollment:

Subject must be able to understand and provide informed consent;
Male or Female, 18 to 75 years of age;
Candidate for a primary heart transplant (e.g., listed for heart transplant only);
Historical panel reactive antibodies (PRA) less than 30%;
Calculated GFR ≥ 40 mL/minute using the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI);
Female and male subjects with reproductive potential, must agree to use FDA approved methods of birth control for the duration of the study

Inclusion Criteria for Randomization / Post-transplant:

--Negative PRA within 12 weeks prior to transplant (Local HLA Center Testing) using one of the following:

One Lambda's LABScreen® Mixed Class I & II (presence or absence), or
Less than 10% by One Lambda's LABScreen® PRA Class I and II with an MFI of <2000, or
Calculated panel reactive antibodies (cPRA) less than 10% by LABScreen® Single Antigen testing (Anti-HLA-A, -B, -DR, -DQ). The antigens reported will include those with an MFI >2000.

The Luminex Gen-Probe beads are equivalent to the One Lambda and may be used as an alternative;

Calculated GFR ≥ 40mL/minute using the CKD-EPI at time of randomization;
Serum immunoglobulin G (IgG) level greater than 500mg/dL within 90 days prior to randomization;
Negative test for HIV, HBsAg, HBcAb, and HCV Ab within 12 months prior to transplant. If documentation is not present to support that the testing was performed in the past 12 months, then a blood sample will be collected prior to transplant and sent for local testing. Results may be available after randomization. If positive result, the oversight committee will review the case and provide further recommendations.
Female subjects of childbearing potential must have a negative pregnancy test.

Exclusion Criteria for Enrollment:

Prior history of organ transplantation;
Previous treatment with Rituximab (MabThera® / Rituxan ®);
Transplant physician intention to use any induction agents;
History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
History of severe reaction to previous therapy with IVIG;
Active systemic infection at time of enrollment;
Any history of serologic positivity to HIV, HBsAg, HBcAb, and HCV Ab;
History of less than 5 years remission of malignancy. Any history of adequately treated in-situ cervical carcinoma, or adequately treated basal or squamous cell carcinoma of the skin will be permitted;
Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
Use of other investigational drugs within 4 weeks of enrollment;
Currently breast-feeding or plans to become pregnant during the timeframe of the study follow-up period.

Exclusion Criteria for Randomization/Post-transplant:

Recipient of multiple solid organ or tissue transplants;
Previous treatment with Rituximab (MabThera® / Rituxan ®);
Use of any induction agents;
History of severe allergic anaphylactic reactions to humanized or murine monoclonal antibodies;
History of severe reaction to previous therapy with IVIG; Lack of IV venous access;
Active systemic infection at time of randomization;
Any history of serologic positivity to HIV, HBsAg, HBcAb and HCV Ab;
Any condition that, in the opinion of the investigator, would interfere with the subject's ability to comply with study requirements;
Use of other investigational drugs within 4 weeks prior to randomization;
Receipt of a live vaccine within 30 days prior to randomization;
Currently breast-feeding or plans to become pregnant during the timeframe of the study follow-up period.

Contacts/Locations Module

Overall Officials

Name	Affiliation	Role
Randall Starling, MD	The Cleveland Clinic	Study Chair
Mohamed Sayegh, MD	Brigham and Women's Hospital/Harvard	Principal Investigator
Anil Chandraker, MD	Brigham and Women's Hospital/Harvard	Study Chair

Facility	Status	City	State	ZIP	Country	Contacts
Cedars Sinai Heart Institute		Beverly Hills	California	90211	United States
Ronald Regan UCLA Medical Center

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
31272550	Result	Starling RC, Armstrong B, Bridges ND, Eisen H, Givertz MM, Kfoury AG, Kobashigawa J, Ikle D, Morrison Y, Pinney S, Stehlik J, Tripathi S, Sayegh MH, Chandraker A; CTOT-11 Study Investigators. Accelerated Allograft Vasculopathy With Rituximab After Cardiac Transplantation. J Am Coll Cardiol. 2019 Jul 9;74(1):36-51. doi: 10.1016/j.jacc.2019.04.056.

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

IPD Sharing Statement Module

No data available

No data is available for this block.

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Submission Tracking

No data available

No data is available for this block.

Condition Browse Module

No data available

No data is available for this block.

Intervention Browse Module

Masking Info

Randomized participants

Arm/Group Information

ID	Title	Description
BG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
BG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
BG002	Total	Total of all reporting groups

Baseline Measures

Title

Description

Population Description

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Denominator Units Selected

Denominators

Classes

Age, Continuous

Mean

Standard Deviation

years

Title

Denominators

Categories

Title	Measurements
	BG00054.6± 11.80 BG00154.8± 11.76 BG00254.7± 11.75

Sex: Female, Male

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Female	BG00016 BG0018 BG002

Ethnicity (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
Hispanic or Latino	BG0009 BG0017 BG002

Race (NIH/OMB)

Count of Participants

Participants

Title

Denominators

Categories

Title	Measurements
American Indian or Alaska Native	BG0000 BG0011 BG002

Region of Enrollment

Count of Participants

Participants

Title

Denominators

Categories

United States

Title	Measurements
	BG00089 BG00174 BG002

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

Change in Percent Atheroma Volume (PAV)

Nominal or noticeable change, bad or good, from baseline to 1 year in percent atheroma volume (PAV) which is a measure of the degree of coronary arterial obstruction due to host alloimmune processes measured by intravascular ultrasound (IVUS) in a target coronary artery. Thus a decrease in PAV would be an indicator of less obstruction and a better outcome.

Randomized participants with available data at year one

Posted

Mean

Standard Deviation

percent

Baseline, 1 year

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Units	Counts
Participants	OG00049 OG00137

Title

Denominators

Categories

Title	Measurements
	OG0006.8± 8.21 OG0011.9± 4.38

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		ANCOVA	Adjusted for baseline PAV	0.0019														Superiority or Other (legacy)

Secondary

Death

Participants who died within 12 months post-transplant

Randomized subjects

Posted

Count of Participants

Participants

12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Re-transplantation or Re-listed for Transplantation

Re-transplantation is defined as the receipt of a subsequent heart transplant and re-listed for transplantation is being listed back on the heart transplant list to be re-transplanted.

Randomized participants

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Number of Episodes of Biopsy Proven Acute Rejection (BPAR) of Any Grade Per Participant

The number of times a participant experienced biopsy proven acute rejection (BPAR). Biopsy proven acute rejection is when an examination of tissue removed from the transplanted organ indicates that the subject's immune system is trying to reject the graft. BPAR was defined as a biopsy that met the International Society for Heart & Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory.

Randomized participants with at least one centrally read heart biopsy

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Incidence of BPAR (Any Grade)

The number of subjects who experienced any grade of biopsy proven acute rejection (BPAR) within the clinical trial. Biopsy proven acute rejection is when an examination of tissue removed from the transplanted organ indicates that the subject's immune system is trying to reject the graft. BPAR was defined as a biopsy which met The International Society for Heart & Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory.

Randomized participants with at least one centrally read heart biopsy

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001

Secondary

Incidence of AMR

The number of participants who experienced antibody- mediated rejection (AMR). Antibody-mediated rejection (AMR) occurs when the subject develops antibodies directed against the transplanted heart. This was assessed based on local pathology biopsy reads.

Randomized participants

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Incidence of Cellular Rejection

Cellular Rejection refers to the organ recipient's immune system recognizing a transplanted organ as foreign and mounting a response to it via cellular mechanisms. Cellular rejection was defined as a biopsy which met The International Society for Heart & Lung Transplantation (ISHLT) criteria to be graded as 1R or greater rejection and was determined by a single, central pathology laboratory

Randomized participants with at least one centrally read heart biopsy

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo

Secondary

Incidence of Any Treated Rejection

The number of participants who were treated by their local physician for any type of rejection including, but not limited to cellular rejection and antibody- mediated rejection (AMR) of the transplanted heart regardless of the presence of a biopsy.

Randomized participants

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Number of Participants With Episodes of Rejection Associated With Hemodynamic Compromise (HDC)

The number of participants that experienced at least one episode of rejection associated with hemodynamic compromise (HDC). Rejection associated with HDC is when there is insufficient blood flow to the transplanted heart in association with acute rejection found in a biopsy. Local biopsies were used for this outcome measure.

Randomized participants

Posted

Count of Participants

Participants

6 to 12 months

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Number of Participants With Development of Angiographically Evident Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy is an aggressive form of atherosclerosis that is characterized by the development of fibrosis affecting cardiac arteries that result in concentric narrowing of the arteries and, ultimately allograft failure. Development of cardiac allograft vasculopathy can be diagnosed via an angiograph which is an X-ray of the cardiac arteries by injecting a radiopaque substance such as iodine.

Randomized participants

Posted

Count of Participants

Participants

1 year

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo

Secondary

Number of Participants With Post-transplant Serious Infections Requiring Intravenous Antimicrobial Therapy

Number of participants experiencing at least one serious infection requiring intravenous antimicrobial therapy which is used to kill the growth of microorganisms such as bacteria, fungi, or protozoans.

Randomized participants

Posted

Count of Participants

Participants

Transplantation through end of study, up to 1 year post transplantation.

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Number of Participants With Post-transplant Incidence of PTLD

The number of participants experiencing at least one post-transplant lymphoproliferative disorder (PTLD) occurrence during this trial. Post-transplant lymphoproliferative disorder is an uncontrolled proliferation of B cell lymphocytes latently infected with Epstein-Barr virus.

Randomized participants

Posted

Count of Participants

Participants

Transplantation through end of study, up to 1 year post transplantation.

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.

Secondary

Post-transplant Safety Outcomes Among Participants: Safety and Tolerability of Rituximab

Defined as participants that experienced at least one adverse event that was possibly, probably, or definitely related to the study drug (i.e., Rituximab or Placebo). Serious adverse events were used to evaluate this endpoint and the attribution was based on the DAIT Medical Monitor's assessment.

Randomized participants

Posted

Count of Participants

Participants

Transplantation through end of study, up to 1 year post transplantation

ID	Title	Description
OG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.
OG001	Placebo

Arm/Groups

ID	Title	Description	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Rituximab	Induction: Rituximab was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.	55	89	29	89
EG001	Placebo	Induction: Rituximab Placebo was administered in 2 1000 mg doses on Day 0 and Day 12 (+/- 2 days). Maintenance: Mycophenolate Mofetil (MMF) was given at a starting dose of 2-3 g by mouth or intravenously per day in 2 or 3 divided doses. Investigator could choose an alternative treatment if needed. Methylprednisolone/Prednisone dosing was administered according to the local center standard. After 6 months, prednisone was withdrawn at the discretion of the investigator. The suggested oral prednisone taper was Day 14: 20 mg/day by mouth, Day 30: 15 mg/day by mouth, Day 90: 10 mg/day by mouth, Day 180: 5 mg/day by mouth, and greater than Day 180: 0-5 mg/day by mouth. Tacrolimus, was administered per site standards to attain target trough levels. The target whole blood tacrolimus concentrations were as follows: Day 1-30 post transplant 10-20 ng/mL and Day 31-Month 12 5-15 ng/mL.	45	74	26	74
EG002	Discontinued Pre-Transplant	Subjects that enrolled, but withdrew from the study prior to their transplant.	0	121	0	121
EG003	Discontinued Pre-Randomization	Subjects that were enrolled and transplanted on study, but withdrew from the study prior to randomization.	1	78	0	78

Serious Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG0030 events0 affected78 at risk
Febrile neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Leukocytosis	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Leukopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Neutropenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Thrombocytopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Atrial flutter	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Atrial tachycardia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Bradycardia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Cardiac failure acute	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Cardiac failure congestive	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Cardiac tamponade	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Coronary artery disease	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Left ventricular dysfunction	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Palpitations	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Pericardial effusion	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0012 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Right ventricular failure	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Supraventricular tachycardia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Tachycardia paroxysmal	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Tricuspid valve incompetence	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Ventricular arrhythmia	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Ventricular fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Thyroiditis	Endocrine disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Colitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Gastritis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Gastrointestinal ulcer haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Gingivitis	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Mouth ulceration	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Nausea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Odynophagia	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Retroperitoneal haemorrhage	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Small intestinal obstruction	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Vomiting	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Fatigue	General disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Generalised oedema	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Multi-organ failure	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Non-cardiac chest pain	General disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Cholecystitis acute	Hepatobiliary disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Transplant rejection	Immune system disorders	MedDRA 13.1	Systematic Assessment	EG00010 events10 affected89 at risk EG00114 events10 affected74 at risk EG0020 events0 affected121 at risk EG003
Abscess limb	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Actinomycosis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Aspergillosis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Cellulitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Clostridial infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Cytomegalovirus viraemia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Fungal infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Fungal skin infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Gastroenteritis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Gastroenteritis viral	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Groin infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Incision site infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Influenza	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Lobar pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Mediastinitis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Nocardiosis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Parvovirus infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Pneumonia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0006 events6 affected89 at risk EG0016 events6 affected74 at risk EG0020 events0 affected121 at risk EG003
Rhinovirus infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Sepsis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0012 events2 affected74 at risk EG0020 events0 affected121 at risk EG003
Septic shock	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Staphylococcal bacteraemia	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Systemic mycosis	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Upper respiratory tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Viral infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Viral upper respiratory tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Wound infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0012 events2 affected74 at risk EG0020 events0 affected121 at risk EG003
Anaemia postoperative	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Complications of transplanted heart	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Seroma	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Spinal fracture	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Vena cava injury	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Wound dehiscence	Injury, poisoning and procedural complications	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Immunosuppressant drug level decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
International normalised ratio increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Troponin I increased	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Weight decreased	Investigations	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Decreased appetite	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Dehydration	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Fluid overload	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Hyperglycaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0002 events2 affected89 at risk EG0012 events2 affected74 at risk EG0020 events0 affected121 at risk EG003
Hyperkalaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Hypervolaemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Hyponatraemia	Metabolism and nutrition disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Back pain	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Compartment syndrome	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Gouty arthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Intervertebral disc protrusion	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Rheumatoid arthritis	Musculoskeletal and connective tissue disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Metastatic neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Presyncope	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Syncope	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Transient ischaemic attack	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0003 events3 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Delirium	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Depression	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Mental status changes	Psychiatric disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0006 events6 affected89 at risk EG0014 events4 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal impairment	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal infarct	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal injury	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Metrorrhagia	Reproductive system and breast disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Diaphragmatic hernia	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Haemoptysis	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Hydropneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Lung infiltration	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Pneumothorax	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Pulmonary embolism	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0012 events2 affected74 at risk EG0020 events0 affected121 at risk EG003
Respiratory distress	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Respiratory failure	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0004 events3 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Arterial haemorrhage	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Deep vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Haematoma	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Haemorrhage	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Intra-abdominal haematoma	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003
Jugular vein thrombosis	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Lymphocele	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0013 events2 affected74 at risk EG0020 events0 affected121 at risk EG003
Orthostatic hypotension	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0010 events0 affected74 at risk EG0020 events0 affected121 at risk EG003
Venous insufficiency	Vascular disorders	MedDRA 13.1	Systematic Assessment	EG0000 events0 affected89 at risk EG0011 events1 affected74 at risk EG0020 events0 affected121 at risk EG003

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anaemia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0008 events8 affected89 at risk EG0017 events7 affected74 at risk EG0020 events0 affected121 at risk EG0030 events0 affected78 at risk
Leukopenia	Blood and lymphatic system disorders	MedDRA 13.1	Systematic Assessment	EG0007 events7 affected89 at risk EG0017 events6 affected74 at risk EG0020 events0 affected121 at risk EG003
Atrial fibrillation	Cardiac disorders	MedDRA 13.1	Systematic Assessment	EG0001 events1 affected89 at risk EG0014 events4 affected74 at risk EG0020 events0 affected121 at risk EG003
Diarrhoea	Gastrointestinal disorders	MedDRA 13.1	Systematic Assessment	EG0005 events5 affected89 at risk EG0014 events4 affected74 at risk EG0020 events0 affected121 at risk EG003
Urinary tract infection	Infections and infestations	MedDRA 13.1	Systematic Assessment	EG0007 events7 affected89 at risk EG0015 events4 affected74 at risk EG0020 events0 affected121 at risk EG003
Headache	Nervous system disorders	MedDRA 13.1	Systematic Assessment	EG0005 events2 affected89 at risk EG0014 events4 affected74 at risk EG0020 events0 affected121 at risk EG003
Renal failure acute	Renal and urinary disorders	MedDRA 13.1	Systematic Assessment	EG0007 events7 affected89 at risk EG0016 events6 affected74 at risk EG0020 events0 affected121 at risk EG003
Pleural effusion	Respiratory, thoracic and mediastinal disorders	MedDRA 13.1	Systematic Assessment	EG0006 events6 affected89 at risk EG0012 events2 affected74 at risk EG0020 events0 affected121 at risk EG003

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

Certain Agreements

ID	Term
D016559	Tacrolimus

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

ID	Term
D018942	Macrolides
D007783	Lactones
D009930	Organic Chemicals