Antibody-mediated RejectionPhase 3DUETNCT02013037
The De-novo Use of Eculizumab in Presensitized Patients Receiving Cardiac Transplantation
A Phase 3 study testing Eculizumab in people with Antibody-mediated Rejection and Hyperacute Rejection of Cardiac Transplant, run by Cedars-Sinai Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Antibody-mediated Rejection, Hyperacute Rejection of Cardiac Transplant, Left Ventricular Dysfunction
- What is being tested?
- Eculizumab
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2012to 30 Apr 2020
- Phase
- Phase 3
- 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
- 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of any study-related procedure not considered routine medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care.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.
Who cannot join
- 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).
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- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Cedars Sinai Medical Center, Heart Institute
Los Angeles, California, 90048
About this study
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]
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.
Read the 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.
- Conditions
- Antibody-mediated Rejection, Hyperacute Rejection of Cardiac Transplant, Left Ventricular Dysfunction, Cardiac Allograft Vasculopathy, Heart Graft Dysfunction
- Being tested
- Eculizumab
- Keywords
- 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
- Medical subject headings
- Ventricular Dysfunction, Left, Complement Component 3 Deficiency, Autosomal Recessive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EculizumabDrug
Also called Soliris
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.
| Study group | Role | What they receive |
|---|---|---|
| Eculizumab | Experimental | 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. Receives: Drug: Eculizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants of Pathologic Antibody-Mediated Rejection and Left Ventricular Dysfunction
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.
Measured: up to 26 weeks post heart transplant
Secondary outcomes (7)
Patient Survival at 12 Months Post Heart Transplantation
The study will assess overall survival at 12 months following heart transplantation.
Measured: 1 year post heart transplant
Number of Participants With Hemodynamic Compromise at 6 Months Post 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
Measured: 6 months post heart transplant
Number of Participants With Hemodynamic Compromise at 1 Year Post 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
Measured: 1 year post heart transplant
Number of Participants With Antibody Mediated Rejection (AMR)
The study assessed the number of patients who develop AMR as well as the total number of episodes of AMR.
Measured: up to 1 year post heart transplant
Number of Participants With of Acute Cellular Rejection (ACR)
The study assessed the number of participants with of Acute Cellular Rejection (ACR)
Measured: up to 1 year post heart transplant
Development of Cardiac Allograft Vasculopathy (CAV) by Intravascular Ultrasound (IVUS)
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.
Measured: up to 1 year post heart transplant
Number of Participants With Evolution of DSA: Donor Specific Antibody Post Transplantation
Number of Participants who develop de novo donor specific antibody (DSA) in the first year following transplantation was determined.
Measured: Up to 1 year post transplant
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2013 (estimated)
- Study startNov 2012
- Primary completion30 Dec 2019
- Study completion30 Apr 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (14)Papers the sponsor has linked to this study.
- Other trials for Antibody-mediated RejectionStudies of the same condition, open and under way.
- More trials run by Cedars-Sinai Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 36 participants (actual)
Sponsor and investigators
- Lead sponsor
- Cedars-Sinai Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Responsible party
- Principal investigator, Jignesh Patel, MD, PhD, Cedars-Sinai Medical Center
- Investigators
- Jignesh Patel, M.D., Ph.D., Principal investigator, Cedars Sinai Medical Center and Heart Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02013037
- Sponsor's protocol ID
- CSR 205237
- Other IDs
- Pro00028970
- Acronym
- DUET
- Status last verified
- Apr 2021
- First submitted
- 11 Dec 2013
- Last updated
- 3 May 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that supports the results of the study after deidentification and in accordance with Cedars Sinai data sharing agreements.
Publications
Kfoury AG, Hammond ME, Snow GL, Drakos SG, Stehlik J, Fisher PW, Reid BB, Everitt MD, Bader FM, Renlund DG. Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellular and antibody-mediated rejection. J Heart Lung Transplant. 2009 Aug;28(8):781-4. doi: 10.1016/j.healun.2009.04.035.
PubMed 19632573Uber WE, Self SE, Van Bakel AB, Pereira NL. Acute antibody-mediated rejection following heart transplantation. Am J Transplant. 2007 Sep;7(9):2064-74. doi: 10.1111/j.1600-6143.2007.01900.x. Epub 2007 Jul 5.
PubMed 17614978Wu GW, Kobashigawa JA, Fishbein MC, Patel JK, Kittleson MM, Reed EF, Kiyosaki KK, Ardehali A. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009 May;28(5):417-22. doi: 10.1016/j.healun.2009.01.015. Epub 2009 Mar 14.
PubMed 19416767Michaels PJ, Espejo ML, Kobashigawa J, Alejos JC, Burch C, Takemoto S, Reed EF, Fishbein MC. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant. 2003 Jan;22(1):58-69. doi: 10.1016/s1053-2498(02)00472-2.
PubMed 12531414Stegall MD, Diwan T, Raghavaiah S, Cornell LD, Burns J, Dean PG, Cosio FG, Gandhi MJ, Kremers W, Gloor JM. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011 Nov;11(11):2405-13. doi: 10.1111/j.1600-6143.2011.03757.x. Epub 2011 Sep 22.
PubMed 21942930Nwakanma LU, Williams JA, Weiss ES, Russell SD, Baumgartner WA, Conte JV. Influence of pretransplant panel-reactive antibody on outcomes in 8,160 heart transplant recipients in recent era. Ann Thorac Surg. 2007 Nov;84(5):1556-62; discussion 1562-3. doi: 10.1016/j.athoracsur.2007.05.095.
PubMed 17954062Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, Burke M, Czer L, Hiemann N, Kfoury AG, Mancini D, Mohacsi P, Patel J, Pereira N, Platt JL, Reed EF, Reinsmoen N, Rodriguez ER, Rose ML, Russell SD, Starling R, Suciu-Foca N, Tallaj J, Taylor DO, Van Bakel A, West L, Zeevi A, Zuckermann A; Consensus Conference Participants. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2011 Mar;30(3):252-69. doi: 10.1016/j.healun.2010.11.003.
PubMed 21300295Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015. No abstract available.
PubMed 21555100Locke JE, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT, King KE, Kraus E, Lees LM, Melancon JK, Stewart ZA, Warren DS, Zachary AA, Montgomery RA. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant. 2009 Jan;9(1):231-5. doi: 10.1111/j.1600-6143.2008.02451.x. Epub 2008 Oct 31.
PubMed 18976298Wang H, Arp J, Liu W, Faas SJ, Jiang J, Gies DR, Ramcharran S, Garcia B, Zhong R, Rother RP. Inhibition of terminal complement components in presensitized transplant recipients prevents antibody-mediated rejection leading to long-term graft survival and accommodation. J Immunol. 2007 Oct 1;179(7):4451-63. doi: 10.4049/jimmunol.179.7.4451.
PubMed 17878341Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol. 1996 Dec;33(17-18):1389-401. doi: 10.1016/s0161-5890(96)00078-8.
PubMed 9171898Rinder CS, Rinder HM, Smith BR, Fitch JC, Smith MJ, Tracey JB, Matis LA, Squinto SP, Rollins SA. Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation. J Clin Invest. 1995 Sep;96(3):1564-72. doi: 10.1172/JCI118195.
PubMed 7657827Coutance G, Kobashigawa JA, Kransdorf E, Loupy A, Desire E, Kittleson M, Patel JK. Intermediate-term outcomes of complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients. J Heart Lung Transplant. 2023 Oct;42(10):1464-1468. doi: 10.1016/j.healun.2023.05.005. Epub 2023 May 12.
PubMed 37182818Patel JK, Coutance G, Loupy A, Dilibero D, Hamilton M, Kittleson M, Kransdorf E, Azarbal B, Seguchi O, Zhang X, Chang D, Geft D, Czer L, Varnous S, Kobashigawa JA. Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients. Am J Transplant. 2021 Jul;21(7):2479-2488. doi: 10.1111/ajt.16420. Epub 2021 Feb 11.
PubMed 33251691
Study at a glance
From the registry record, last updated by the sponsor on 3 May 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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]
- ClinicalTrials.gov ID
- NCT02013037
- Acronym / sponsor ID
- DUET / CSR 205237
- Conditions
- Antibody-mediated Rejection, Hyperacute Rejection of Cardiac Transplant, Left Ventricular Dysfunction, Cardiac Allograft Vasculopathy, Heart Graft Dysfunction
- Keywords
- cardiac transplantation, immunosuppression, acute cellular rejection, antibody mediated rejection, sensitization, antibody production in cardiac patients, panel reactive antibodies, desensitization strategies in heart transplant patients
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 36 participants (actual)
- Lead sponsor
- Cedars-Sinai Medical CenterUniversity, hospital or other
- Collaborators
- Alexion Pharmaceuticals, Inc.
- Study start
- Nov 2012
- Primary completion
- 30 Dec 2019 (actual)
- Study completion
- 30 Apr 2020 (actual)
- First posted
- 17 Dec 2013 (estimated)
- Results
- Posted 3 May 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Eculizumab | Experimental | Drug: EculizumabAdministration 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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| EculizumabAlso: SolirisAt 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. | Drug | Eculizumab |
Primary outcome
Number of Participants of Pathologic Antibody-Mediated Rejection and Left Ventricular Dysfunction
Time frame: up to 26 weeks post heart transplant
The efficacy of Eculizumab will be assessed by a composite endpoint of: 1. the incidence of pathologic AMR with a Grade ≥ 2 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.
7 secondary outcomes
Patient Survival at 12 Months Post Heart Transplantation
Time frame: 1 year post heart transplant
Number of Participants With Hemodynamic Compromise at 6 Months Post Transplant
Time frame: 6 months post heart transplant
Number of Participants With Hemodynamic Compromise at 1 Year Post Transplant
Time frame: 1 year post heart transplant
Number of Participants With Antibody Mediated Rejection (AMR)
Time frame: up to 1 year post heart transplant
Number of Participants With of Acute Cellular Rejection (ACR)
Time frame: up to 1 year post heart transplant
Development of Cardiac Allograft Vasculopathy (CAV) by Intravascular Ultrasound (IVUS)
Time frame: up to 1 year post heart transplant
Number of Participants With Evolution of DSA: Donor Specific Antibody Post Transplantation
Time frame: Up to 1 year post transplant
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 May 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 19632573Kfoury AG, Hammond ME, Snow GL, Drakos SG, Stehlik J, Fisher PW, Reid BB, Everitt MD, Bader FM, Renlund DG. Cardiovascular mortality among heart transplant recipients with asymptomatic antibody-mediated or stable mixed cellular and antibody-mediated rejection. J Heart Lung Transplant. 2009 Aug;28(8):781-4. doi: 10.1016/j.healun.2009.04.035.
- Background: PubMed 17614978Uber WE, Self SE, Van Bakel AB, Pereira NL. Acute antibody-mediated rejection following heart transplantation. Am J Transplant. 2007 Sep;7(9):2064-74. doi: 10.1111/j.1600-6143.2007.01900.x. Epub 2007 Jul 5.
- Background: PubMed 19416767Wu GW, Kobashigawa JA, Fishbein MC, Patel JK, Kittleson MM, Reed EF, Kiyosaki KK, Ardehali A. Asymptomatic antibody-mediated rejection after heart transplantation predicts poor outcomes. J Heart Lung Transplant. 2009 May;28(5):417-22. doi: 10.1016/j.healun.2009.01.015. Epub 2009 Mar 14.
- Background: PubMed 12531414Michaels PJ, Espejo ML, Kobashigawa J, Alejos JC, Burch C, Takemoto S, Reed EF, Fishbein MC. Humoral rejection in cardiac transplantation: risk factors, hemodynamic consequences and relationship to transplant coronary artery disease. J Heart Lung Transplant. 2003 Jan;22(1):58-69. doi: 10.1016/s1053-2498(02)00472-2.
- Background: PubMed 21942930Stegall MD, Diwan T, Raghavaiah S, Cornell LD, Burns J, Dean PG, Cosio FG, Gandhi MJ, Kremers W, Gloor JM. Terminal complement inhibition decreases antibody-mediated rejection in sensitized renal transplant recipients. Am J Transplant. 2011 Nov;11(11):2405-13. doi: 10.1111/j.1600-6143.2011.03757.x. Epub 2011 Sep 22.
- Background: PubMed 17954062Nwakanma LU, Williams JA, Weiss ES, Russell SD, Baumgartner WA, Conte JV. Influence of pretransplant panel-reactive antibody on outcomes in 8,160 heart transplant recipients in recent era. Ann Thorac Surg. 2007 Nov;84(5):1556-62; discussion 1562-3. doi: 10.1016/j.athoracsur.2007.05.095.
- Background: PubMed 21300295Kobashigawa J, Crespo-Leiro MG, Ensminger SM, Reichenspurner H, Angelini A, Berry G, Burke M, Czer L, Hiemann N, Kfoury AG, Mancini D, Mohacsi P, Patel J, Pereira N, Platt JL, Reed EF, Reinsmoen N, Rodriguez ER, Rose ML, Russell SD, Starling R, Suciu-Foca N, Tallaj J, Taylor DO, Van Bakel A, West L, Zeevi A, Zuckermann A; Consensus Conference Participants. Report from a consensus conference on antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2011 Mar;30(3):252-69. doi: 10.1016/j.healun.2010.11.003.
- Background: PubMed 21555100Berry GJ, Angelini A, Burke MM, Bruneval P, Fishbein MC, Hammond E, Miller D, Neil D, Revelo MP, Rodriguez ER, Stewart S, Tan CD, Winters GL, Kobashigawa J, Mehra MR. The ISHLT working formulation for pathologic diagnosis of antibody-mediated rejection in heart transplantation: evolution and current status (2005-2011). J Heart Lung Transplant. 2011 Jun;30(6):601-11. doi: 10.1016/j.healun.2011.02.015. No abstract available.
- Background: PubMed 18976298Locke JE, Magro CM, Singer AL, Segev DL, Haas M, Hillel AT, King KE, Kraus E, Lees LM, Melancon JK, Stewart ZA, Warren DS, Zachary AA, Montgomery RA. The use of antibody to complement protein C5 for salvage treatment of severe antibody-mediated rejection. Am J Transplant. 2009 Jan;9(1):231-5. doi: 10.1111/j.1600-6143.2008.02451.x. Epub 2008 Oct 31.
- Background: PubMed 17878341Wang H, Arp J, Liu W, Faas SJ, Jiang J, Gies DR, Ramcharran S, Garcia B, Zhong R, Rother RP. Inhibition of terminal complement components in presensitized transplant recipients prevents antibody-mediated rejection leading to long-term graft survival and accommodation. J Immunol. 2007 Oct 1;179(7):4451-63. doi: 10.4049/jimmunol.179.7.4451.
- Background: PubMed 9171898Thomas TC, Rollins SA, Rother RP, Giannoni MA, Hartman SL, Elliott EA, Nye SH, Matis LA, Squinto SP, Evans MJ. Inhibition of complement activity by humanized anti-C5 antibody and single-chain Fv. Mol Immunol. 1996 Dec;33(17-18):1389-401. doi: 10.1016/s0161-5890(96)00078-8.
- Background: PubMed 7657827Rinder CS, Rinder HM, Smith BR, Fitch JC, Smith MJ, Tracey JB, Matis LA, Squinto SP, Rollins SA. Blockade of C5a and C5b-9 generation inhibits leukocyte and platelet activation during extracorporeal circulation. J Clin Invest. 1995 Sep;96(3):1564-72. doi: 10.1172/JCI118195.
- Individual participant dataSharing planned: Yes. Individual participant data that supports the results of the study after deidentification and in accordance with Cedars Sinai data sharing agreements.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jignesh Patel, M.D., Ph.D. principal investigator
Cedars Sinai Medical Center and Heart Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Eculizumab in people with Antibody-mediated Rejection and Hyperacute Rejection of Cardiac Transplant, run by Cedars-Sinai Medical Center at 1 site 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 6 inclusion and 10 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: finished, as of the sponsor's last update on 3 May 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 3 May 2021). 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?
Number of Participants of Pathologic Antibody-Mediated Rejection and Left Ventricular Dysfunction (time frame: up to 26 weeks post heart transplant). 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 NCT02013037, which also lists 14 linked publications.
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 3 May 2021.