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Cardiac Allograft VasculopathyPhase 2NCT01278745

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

A Phase 2 study testing Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper) in people with Cardiac Allograft Vasculopathy and Heart Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

All people who have a heart transplant are at risk for developing cardiac allograft vasculopathy (CAV). CAV means narrowing of the heart transplant vessels, which is associated with poor heart transplant function. People who develop antibodies after transplant have a higher risk of developing CAV. Read more about this study

Who is it for?
Ages 18 to 75 years
What is being tested?
Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
362 participants
Where
24 sitesUnited States
Study dates
Sep 2011to Oct 2015
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • --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.

Who cannot join

  • 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;
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  • 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.
  • 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.

Trial locations and contacts

24 sites in 1 country.

24 sites in 1 country

United States24 sites

  • University of Maryland

    Baltimore, Maryland, 21201

  • Cedars Sinai Heart Institute

    Beverly Hills, California, 90211

  • Tufts Medical Center

    Boston, Massachusetts, 02111

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02115

  • Medical University of South Carolina

    Charleston, South Carolina, 29425

  • Northwestern University

    Chicago, Illinois, 60611

  • Cleveland Clinic Foundation

    Cleveland, Ohio, 44195

  • Medical City Dallas Hospital/CRSTI

    Dallas, Texas, 75230

  • The Methodist Hospital

    Houston, Texas, 77030

  • Ronald Regan UCLA Medical Center

    Los Angeles, California, 90095

  • University of Wisconsin

    Madison, Wisconsin, 53792

  • Minneapolis Heart Institute

    Minneapolis, Minnesota, 55407

  • University of Minnesota

    Minneapolis, Minnesota, 55455

  • Intermountain Medical Center

    Murray, Utah, 84157

  • Mount Sinai School of Medicine

    New York, New York, 10029

  • Columbia University Medical Center

    New York, New York, 10032'

  • Stanford University/Palo Alto VA

    Palo Alto, California, 94304

  • Drexel University College of Medicine

    Philadelphia, Pennsylvania, 19102

  • University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Allegheny General Hospital

    Pittsburgh, Pennsylvania, 15212

  • University of Utah

    Salt Lake City, Utah, 84132-2401

  • University of California San Francisco

    San Francisco, California, 94143-0124

  • Stanford University

    Stanford, California, 94305

Other trials in United States

About this study

Official title: Prevention of Cardiac Allograft Vasculopathy Using Rituximab (Rituxan) Therapy in Cardiac Transplantation (CTOT-11)

All people who have a heart transplant are at risk for developing cardiac allograft vasculopathy (CAV). CAV means narrowing of the heart transplant vessels, which is associated with poor heart transplant function. People who develop antibodies after transplant have a higher risk of developing CAV. Infections, high cholesterol, and rejection also increase the risk of developing CAV. People who develop CAV usually have to receive another transplant.

Read the detailed description

The purpose of this research study is to see if a study drug called rituximab (Rituxan®) prevents CAV. Rituximab destroys certain types of white blood cells called B cells. B cells are important cells in the immune system that help the body fight infection by producing substances called antibodies. B cells and the antibodies they produce are also involved in some kinds of rejection after organ transplantation. Rituximab decreases the number of B cells in the blood and other tissues. The goal of this study is to determine if decreasing B cells with Rituximab can prevent injury to the transplanted heart.

Being tested
Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper), Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Keywords
cardiac allograft vasculopathy (CAV), prevention, cardiac transplantation, rituximab

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)Biological

  • Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)Drug

Study groups in NCT01278745
Study groupRoleWhat they receive
RituximabExperimentalRituximab induction/conventional immunosuppression
Receives: Biological: Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper)
Rituximab PlaceboPlacebo comparatorRituximab Placebo / conventional immunosuppression
Receives: Drug: Rituximab placebo/conventional immunosuppression (tacrolimus, MMF, and steroid taper)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: Baseline, 1 year

Secondary outcomes (12)

  1. Death

    Participants who died within 12 months post-transplant

    Measured: 12 months

  2. 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.

    Measured: 6 to 12 months

  3. 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.

    Measured: 6 to 12 months

  4. 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.

    Measured: 6 to 12 months

  5. 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.

    Measured: 6 to 12 months

  6. 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

    Measured: 6 to 12 months

  7. 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.

    Measured: 6 to 12 months

  8. 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.

    Measured: 6 to 12 months

  9. 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.

    Measured: 1 year

  10. 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.

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

  11. 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.

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

  12. 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.

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Jan 2011 (estimated)
  2. Study startSep 2011
  3. Primary completionOct 2015
  4. Study completionOct 2015

Why it stopped: Due to inability to meet accrual goals within the funding period

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
362 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01278745
Sponsor's protocol ID
DAIT CTOT-11
Status last verified
Sep 2026
First submitted
16 Jan 2011
Last updated
24 Sep 2026
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 31272550

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Rituximab induction/conventional immunosuppression (tacrolimus, MMF, and steroid taper) in people with Cardiac Allograft Vasculopathy and Heart Transplant Recipients, run by National Institute of Allergy and Infectious Diseases (NIAID) at 24 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: stopped early, as of the sponsor's last update on 24 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 24 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Apr 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Percent Atheroma Volume (PAV) (time frame: Baseline, 1 year). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01278745, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Sep 2026.

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