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DUET: The De-novo Use of Eculizumab in Presensitized Patients Receiving Cardiac Transplantation

Sponsor
Cedars-Sinai Medical Center (Other)
Overall Status
Completed
CT.gov ID
NCT02013037
Collaborator
Alexion Pharmaceuticals (Industry)
36
Enrollment
1
Location
1
Arm
89.9
Duration (Months)
0.4
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

All individuals who receive a heart transplant are at risk for developing antibody-mediated rejection (AMR). An antibody is a protein produced by the body's immune system when it detects a foreign substance, called an antigen. The mechanism of an antibody is to attack an antigen. In antibody mediated rejection, antibodies will attack the transplanted heart, causing injury to the heart. The purpose of this investigation is to determine if a study drug, called eculizumab (Soliris), is safe to use in heart transplant recipients, and determine if it reduces risk of antibody-mediated rejection.

Condition or Disease Intervention/Treatment Phase
Phase 3

Detailed Description

The growing proportion of sensitized cardiac recipients presents an additional challenge to the transplant practitioner attempting to minimize the occurrence of antibody mediated rejection (AMR). Patients pre-exposed or "sensitized" to antigen exposing events (i.e.: blood transfusions, multiple pregnancies, prior organ transplantations, ventricular support devices) are more likely to both possess preformed and develop de-novo antibodies. Sensitized patients with panel reactive antibodies > 25% are at risk for increased risk of rejection, development of cardiac allograft vasculopathy and increased mortality after heart transplantation.

A central component of antibody-mediated cell injury is complement activation. The inhibition of terminal complement activation may be the missing link to decreasing possibly both complement-mediated AMR and cellular rejection (CR) by inhibiting both the inflammatory effects of both circulating antibodies and cytokine induced cell death.

Eculizumab is a monoclonal antibody that specifically binds to complement protein C5 with high affinity, thereby inhibiting its cleavage to C5a and C5b and preventing the generation of the terminal complement complex C5b-9. By this mechanism, eculizumab (Soliris®) inhibits terminal complement mediated intravascular hemolysis in paroxysmal nocturnal hemoglobinuria patients.

This study is a non-randomized, open-label, investigator-initiated safety and efficacy trial investigating the de-novo use of eculizumab alongside conventional therapy to prevent antibody mediated rejection. The duration of the study will include an open enrollment period and at least 12 months of follow-up (post-transplant). We will consent up to 45 eligible patients, highly "sensitized", with a panel reactive antibody score greater than 70%, who are not previously or currently enrolled in another ongoing trial. Of these 45 participants, up to 20 of these patients will be treated with eculizumab (Solaris), the study drug. The use of eculizumab will be un-blinded to all study and research practitioner participants.

Study Design

Study Type:
Interventional
Actual Enrollment :
36 participants
Allocation:
N/A
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
The De-novo Use of Eculizumab Alongside Conventional Therapy in Presensitized Patients Receiving Cardiac Transplantation: An Open-Label, Investigator-Initiated Pilot Trial: [The DUET Cardiac Trial]
Study Start Date :
Nov 1, 2012
Actual Primary Completion Date :
Dec 30, 2019
Actual Study Completion Date :
Apr 30, 2020

Arms and Interventions

Arm Intervention/Treatment
Experimental: Eculizumab

Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection.

Drug: Eculizumab
At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
Other Names:
  • Soliris

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Number of Participants of Pathologic Antibody-Mediated Rejection and Left Ventricular Dysfunction [up to 26 weeks post heart transplant]

      The efficacy of Eculizumab will be assessed by a composite endpoint of: the incidence of pathologic AMR with a Grade ≥ 2 the incidence of left ventricular dysfunction, as defined by a left ventricular ejection fraction (LVEF) ≤ 40% or a decrease of >15% from baseline prior to the initiation of Eculizumab treatment.

    Secondary Outcome Measures

    1. Patient Survival at 12 Months Post Heart Transplantation [1 year post heart transplant]

      The study will assess overall survival at 12 months following heart transplantation.

    2. Number of Participants With Hemodynamic Compromise at 6 Months Post Transplant [6 months post heart transplant]

      The incidence of patient hemodynamic compromise will be assessed at 6 months post transplant, as defined by any one of the following: a 20% decrease in LVEF from baseline a LVEF < 40% a 25% decrease in cardiac index from baseline a cardiac index < 2.0 the need for inotropic support

    3. Number of Participants With Hemodynamic Compromise at 1 Year Post Transplant [1 year post heart transplant]

      The incidence of patient hemodynamic compromise will be assessed at one year post transplant, as defined by any one of the following: a 20% decrease in LVEF from baseline a LVEF < 40% a 25% decrease in cardiac index from baseline a cardiac index < 2.0 the need for inotropic support

    4. Number of Participants With Antibody Mediated Rejection (AMR) [up to 1 year post heart transplant]

      The study assessed the number of patients who develop AMR as well as the total number of episodes of AMR.

    5. Number of Participants With of Acute Cellular Rejection (ACR) [up to 1 year post heart transplant]

      The study assessed the number of participants with of Acute Cellular Rejection (ACR)

    6. Development of Cardiac Allograft Vasculopathy (CAV) by Intravascular Ultrasound (IVUS) [up to 1 year post heart transplant]

      Development of cardiac allograft vasculopathy at 1 year determined by intravascular ultrasound defined as change in site-matched maximal intimal thickness ≥ 0.5mm from baseline to 1 year.

    7. Number of Participants With Evolution of DSA: Donor Specific Antibody Post Transplantation [Up to 1 year post transplant]

      Number of Participants who develop de novo donor specific antibody (DSA) in the first year following transplantation was determined.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 75 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:

    • Patient is ≥ 18 years of age.

    • Patient has a panel reactive antibody (PRA) ≥ 70% at any time prior to screening.

    • Patient is considered compliant and intends to be available for a minimum follow-up study period of 1 year.

    • Patient must be vaccinated against Neisseria meningitides at least 2 weeks prior to receiving treatment therapy or receive appropriate antibiotic prophylaxis for the duration of eculizumab treatment if timely vaccination could not be achieved prior to transplantation.

    • Voluntary written informed consent must be obtained before performance of any study-related procedure not considered routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.

    • Female subject is either post-menopausal or surgically sterilized or willing to use two acceptable methods of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study and for up to 2 months after the last dose of study medication.

    Exclusion Criteria:

    • Donor or recipient age is < 18 years or > 75 years.

    • Cold ischemia time is > 6 hours.

    • Current clinical, radiographic, or laboratory evidence of active or latent tuberculosis (TB), as determined by local standard of care.

    • History of active TB within the last 2 years, even if treated.

    • History of active TB greater than 2 years ago, unless there is documentation of adequate treatment according to locally accepted clinical practice.

    (Note: Patients at risk of TB reactivation preclude administration of conventional immunosuppression, as determined by the study investigator and based upon appropriate evaluation).

    • Receipt of desensitization treatment with rituximab less than 2 weeks prior to therapy and cluster of differentiation antigen 20 (CD20) count >2%.

    • Receipt of a live vaccine within 4 weeks prior to study entry.

    • Patients with current or recent severe systemic infections within the 2 weeks prior to transplantation.

    • Prior history of splenectomy.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Cedars Sinai Medical Center, Heart Institute Los Angeles California United States 90048

    Sponsors and Collaborators

    • Cedars-Sinai Medical Center
    • Alexion Pharmaceuticals

    Investigators

    • Principal Investigator: Jignesh Patel, M.D., Ph.D., Cedars Sinai Medical Center and Heart Institute

    Study Documents (Full-Text)

    More Information

    Publications

    Responsible Party:
    Jignesh Patel, MD, PhD, Medical Director of Heart Transplant Program, Cedars Sinai Heart Institute, Cedars-Sinai Medical Center
    ClinicalTrials.gov Identifier:
    NCT02013037
    Other Study ID Numbers:
    • CSR 205237
    • Pro00028970
    First Posted:
    Dec 17, 2013
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    Yes
    Plan to Share IPD:
    Yes
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Product Manufactured in and Exported from the U.S.:
    No
    Keywords provided by Jignesh Patel, MD, PhD, Medical Director of Heart Transplant Program, Cedars Sinai Heart Institute, Cedars-Sinai Medical Center
    cardiac transplantation
    immunosuppression
    acute cellular rejection
    antibody mediated rejection
    sensitization
    antibody production in cardiac patients
    panel reactive antibodies
    desensitization strategies in heart transplant patients
    complement activation
    complement c3d and c4d deposition
    terminal complement inhibition
    complement C5 binding
    Eculizumab
    monoclonal antibody
    donor specific antibodies
    Additional relevant MeSH terms:
    Ventricular Dysfunction
    Ventricular Dysfunction, Left
    Eculizumab

    Study Results

    Participant Flow

    Recruitment Details Participants were enrolled following written informed consent for a protocol approved by the Institutional Review Board of Cedars-Sinai Medical Center (NCT02013037).The duration of the study included an open enrollment period and at least 12 months of post-transplant follow-up. All patients worked up for a heart transplant at the Heart Institute at Cedars-Sinai Medical Center (CSMC) with a panel reactive antibody (PRA) ≥ 70% at any time prior to screening.
    Pre-assignment Detail The trial enrolled a total of 36 sensitized participants age ≥ 18 years with a panel reactive antibody ≥70% at any time prior to study screening. Participants were included in the eculizumab treatment group if at least one donor specific antibody at MFI≥5000 was crossed but with negative prospective complement-dependent cytotoxicity crossmatch. 16 enrolled patients did not receive eculizumab.
    Arm/Group Title Eculizumab
    Arm/Group Description Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Period Title: Overall Study
    STARTED 36
    COMPLETED 20
    NOT COMPLETED 16

    Baseline Characteristics

    Arm/Group Title Eculizumab
    Arm/Group Description Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Overall Participants 20
    Age (years) [Median (Full Range) ]
    Median (Full Range) [years]
    53.3
    Sex: Female, Male (Count of Participants)
    Female
    16
    80%
    Male
    4
    20%
    Race/Ethnicity, Customized (Count of Participants)
    Non-Caucasian
    7
    35%
    Region of Enrollment (participants) [Number]
    United States
    20
    100%
    Non ischemic heart failure (Count of Participants)
    Count of Participants [Participants]
    15
    75%
    Time on waiting list (Days) [Median (Full Range) ]
    Median (Full Range) [Days]
    129
    Long term mechanical circulatory support (MCS) or extra-corporeal membrane oxygena at transplant (Count of Participants)
    Count of Participants [Participants]
    10
    50%
    Combined transplantation (Count of Participants)
    Count of Participants [Participants]
    2
    10%
    Retransplantation (Count of Participants)
    Count of Participants [Participants]
    5
    25%
    Prior blood transfusion (Count of Participants)
    Count of Participants [Participants]
    8
    40%
    Prior pregnancy (women) (Count of Participants)
    Count of Participants [Participants]
    14
    70%
    Pre-transplant diabetes (Count of Participants)
    Count of Participants [Participants]
    7
    35%
    Pre-transplant hypertension (Count of Participants)
    Count of Participants [Participants]
    8
    40%
    Serum creatinine (mg/dL) [Median (Full Range) ]
    Median (Full Range) [mg/dL]
    1.35

    Outcome Measures

    1. Primary Outcome
    Title Number of Participants of Pathologic Antibody-Mediated Rejection and Left Ventricular Dysfunction
    Description The efficacy of Eculizumab will be assessed by a composite endpoint of: the incidence of pathologic AMR with a Grade ≥ 2 the incidence of left ventricular dysfunction, as defined by a left ventricular ejection fraction (LVEF) ≤ 40% or a decrease of >15% from baseline prior to the initiation of Eculizumab treatment.
    Time Frame up to 26 weeks post heart transplant

    Outcome Measure Data

    Analysis Population Description
    [Not Specified]
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    4
    20%
    2. Secondary Outcome
    Title Patient Survival at 12 Months Post Heart Transplantation
    Description The study will assess overall survival at 12 months following heart transplantation.
    Time Frame 1 year post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 participants were included in the Eculizumab study
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    18
    90%
    3. Secondary Outcome
    Title Number of Participants With Hemodynamic Compromise at 6 Months Post Transplant
    Description The incidence of patient hemodynamic compromise will be assessed at 6 months post transplant, as defined by any one of the following: a 20% decrease in LVEF from baseline a LVEF < 40% a 25% decrease in cardiac index from baseline a cardiac index < 2.0 the need for inotropic support
    Time Frame 6 months post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 participants were included in the Eculizumab study
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    0
    0%
    4. Secondary Outcome
    Title Number of Participants With Hemodynamic Compromise at 1 Year Post Transplant
    Description The incidence of patient hemodynamic compromise will be assessed at one year post transplant, as defined by any one of the following: a 20% decrease in LVEF from baseline a LVEF < 40% a 25% decrease in cardiac index from baseline a cardiac index < 2.0 the need for inotropic support
    Time Frame 1 year post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 participants participated in the eculizumab study
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    0
    0%
    5. Secondary Outcome
    Title Number of Participants With Antibody Mediated Rejection (AMR)
    Description The study assessed the number of patients who develop AMR as well as the total number of episodes of AMR.
    Time Frame up to 1 year post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 participants were treated in the eculizumab study
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    6
    30%
    6. Secondary Outcome
    Title Number of Participants With of Acute Cellular Rejection (ACR)
    Description The study assessed the number of participants with of Acute Cellular Rejection (ACR)
    Time Frame up to 1 year post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 participants were treated in the eculizumab study
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    0
    0%
    7. Secondary Outcome
    Title Development of Cardiac Allograft Vasculopathy (CAV) by Intravascular Ultrasound (IVUS)
    Description Development of cardiac allograft vasculopathy at 1 year determined by intravascular ultrasound defined as change in site-matched maximal intimal thickness ≥ 0.5mm from baseline to 1 year.
    Time Frame up to 1 year post heart transplant

    Outcome Measure Data

    Analysis Population Description
    20 enrolled patients were treated on the study
    Arm/Group Title Eculizumab
    Arm/Group Description Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    1
    5%
    8. Secondary Outcome
    Title Number of Participants With Evolution of DSA: Donor Specific Antibody Post Transplantation
    Description Number of Participants who develop de novo donor specific antibody (DSA) in the first year following transplantation was determined.
    Time Frame Up to 1 year post transplant

    Outcome Measure Data

    Analysis Population Description
    20 enrolled patients were treated on the study
    Arm/Group Title Eculizumab
    Arm/Group Description Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit.
    Measure Participants 20
    Count of Participants [Participants]
    5
    25%

    Adverse Events

    Time Frame 1 year post transplant
    Adverse Event Reporting Description
    Arm/Group Title Eculizumab
    Arm/Group Description Administration of Eculizumab to heart transplant recipients at Cedars Sinai Medical Center with a panel reactive antibody (PRA) ≥ 70%, for the prevention of antibody-mediated rejection. Eculizumab: At the time of transplantation, 1200mg of Eculizumab will be administered via a 35 minute IV infusion, followed by thymoglobulin 1.5 mg/kg intravenous piggyback (IVPB). The administration of thymoglobulin will be repeated (if blood counts permit) for a total of five doses. On Day 1 post-transplant, 900 mg of Eculizumab will be given via an IV infusion. On Day 5 post-transplant, intravenous immunoglobulin (IVIG) 1 gram/kg will be administered daily for two consecutive days. On post-transplant days 7, 14, and 21 (+/- 2 days) 900mg of Eculizumab will be given via an IV infusion at each scheduled visit. On post-transplant days 28, 42, and 56 (+/- 2 days) 1200 mg of Eculizumab will be given via an IV infusion at each scheduled visit. 2 deaths were reported in participants who received eculizumab. There were 6 deaths in participants who did not complete the study and did not receive eculizumab.
    All Cause Mortality
    Eculizumab
    Affected / at Risk (%) # Events
    Total 8/36 (22.2%)
    Serious Adverse Events
    Eculizumab
    Affected / at Risk (%) # Events
    Total 13/36 (36.1%)
    Infections and infestations
    Viral infections 6/36 (16.7%) 6
    Bacterial Infections 7/36 (19.4%) 8
    Fungal infections 2/36 (5.6%) 2
    Other (Not Including Serious) Adverse Events
    Eculizumab
    Affected / at Risk (%) # Events
    Total 0/36 (0%)

    Limitations/Caveats

    [Not Specified]

    More Information

    Certain Agreements

    Principal Investigators are NOT employed by the organization sponsoring the study.

    There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

    Results Point of Contact

    Name/Title Dr. Jignesh Patel
    Organization Cedars Sinai Smidt Heart Institute
    Phone 310-248-8300
    Email jignesh.patel@cshs.org
    Responsible Party:
    Jignesh Patel, MD, PhD, Medical Director of Heart Transplant Program, Cedars Sinai Heart Institute, Cedars-Sinai Medical Center
    ClinicalTrials.gov Identifier:
    NCT02013037
    Other Study ID Numbers:
    • CSR 205237
    • Pro00028970
    First Posted:
    Dec 17, 2013
    Last Update Posted:
    May 3, 2021
    Last Verified:
    Apr 1, 2021