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Extracorporeal Photopheresis and Early Cardiac Graft Vasculopathy (ECP-OCT)

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ClinicalTrials.gov Identifier: NCT04226521
Recruitment Status : Recruiting
First Posted : January 13, 2020
Last Update Posted : January 13, 2020
Sponsor:
Collaborator:
University of Zagreb
Information provided by (Responsible Party):
Bosko Skoric, University of Zagreb

Brief Summary:

Heart transplantation is a golden standard for the treatment of terminal heart failure. The major cause of death in late posttransplant period is cardiac allograft vasculopathy (CAV). This posttransplant complication develops slowly over several years, and when diagnosed either by conventional coronary angiography or due to graft failure, it is often too advanced and difficult to treat since it is diffuse coronary artery disease.

Therefore, early prevention of CAV is a subject of major interest in the transplant cardiology. Since CAV is associated with immune factors, immunomodulatory therapeutic options, like extracorporeal photopheresis are lately being investigated.

Unlike conventional coronary angiography, optical coherence tomography (OCT) is able to detect the development of CAV in the earliest phase, i.e. even in the first post-transplant year.

In our study, we plan to investigate the prophylactic effect of extracorporeal photopheresis in the early development of cardiac graft vasculopathy detected by OCT.


Condition or disease Intervention/treatment Phase
Cardiac Allograft Vasculopathy Heart Transplant Rejection Procedure: Extracoropreal photopheresis Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 30 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Patients are randomized after heart transplant into two groups. Those randomized for extracorporeal photopheresis undergo 10 procedures during first year, in addition to standard follow-up. Patients in the control group are treated and followed-up according to standard protocol of our transplant center.
Masking: None (Open Label)
Primary Purpose: Prevention
Official Title: Extracorporeal Photopheresis for the Prevention of Early Cardiac Allograft Vasculopathy Detected by Optical Coherence Tomography
Actual Study Start Date : January 1, 2018
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Photopheresis
Patients who sign informed consent form undergo prophylactic extracorporeal photopheresis after heart transplant according to predetermined protocol
Procedure: Extracoropreal photopheresis
Patients who sign informed consent form undergo prophylactic extracorporeal photopheresis after heart transplant according to predetermined protocol

No Intervention: No prophylactic photopheresis
Standard post-transplant protocol without prophylactic extracorporeal photopheresis



Primary Outcome Measures :
  1. Prevention of cardiac allograft vasculopathy detected by optical coherence tomography [ Time Frame: One year ]
    It will be measured as the mean change in maximal intimal thickness (mm) between matched slices and the mean change in intimal volume (mm3) between matched coronary segments from baseline to month 12. Intima-to-media border will be identified as sharp line between first bright layer (intima) and first dark layer (media) of vessel wall. OCT will be performed during the patient's angiogram at baseline (1-3 months after transplantation) and again at one year after transplantation. An attempt will be made to get OCT image of all three coronary arteries. Two independent experienced angiographers, who will be blinded to clinical data, will review the baseline and follow-up image acquisition sequences to accurately match the coronary segments. We will compare the mean change of maximal intimal thickness (mm) and/or the mean change of intimal volume (mm3) between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo ECP.


Secondary Outcome Measures :
  1. Number of patients with angiographically detected coronary artery disease [ Time Frame: 1 year ]

    Angiographically detected CAV is defined as any new luminal irregularity or new stenosis ≥50% on control coronary angiography at 12 months interval.

    We will compare the incidence of angiographically detected transplant vasculopathy defined as newly occurring angiographic luminal irregularities or ≥50% stenosis between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP).


  2. Number of patients with acute cellular rejection [ Time Frame: 1 year ]
    Patients will be monitored for acute rejection by routine surveillance endomyocardial biopsy at 1, 2, 4, 6, 9 and 12 months after heart transplantation. Graft rejection will be as an acute cellular rejection with histopathology grade ≥1B according to the 1990 International Society of Heart and Lung Transplantation classification and ≥2R according to the 2004 R grading system. For patients with multiple episodes of rejection, the time to the first event will be counted as the censored outcome. A 1-year cumulative total rejection score (TRS) will be assigned as grade 0=0, grade 1A=0.5, grade 1B=1, grade 2=1.5, grade 3A=2, grade 3B=2.5, grade 4=3, or as grade 0R=0, grade 1R = 1, grade 2R=2, grade 3R=3, and normalized by dividing the cumulative scores with the total number of biopsies performed during the 1-year period. We will compare the incidence of acute cellular rejection between patients who underwent ECP to those who did not undergo ECP.

  3. Number of patients with antibody-mediated rejection [ Time Frame: 1 year ]

    Patients will be monitored for antibody-mediated rejection (AMR) by routine surveillance endomyocardial biopsy at 1, 6 and 12 months within the first year after heart transplantation. It will be defined as either positive immunopathologic finding (the presence of C4d deposition in capillaries in the fresh-frozen biopsy sample), positive histopathologic finding or both.

    We will compare the incidence of antibody-mediated rejection between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP).


  4. Number of patients with positive donor specific antibodies [ Time Frame: 1 year ]

    Patients will be monitored for de novo donor specific antibodies (DSA) by routine laboratory surveillance using Luminex assay at 1, 6 and 12 months within the first year after heart transplantation. Positive DSA will be defined as donor-specific antibody with mean fluorescence intensity (MFI) ≥ 2000.

    We will compare the incidence of positive de novo donor specific antibodies between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP).


  5. Left ventricular function expressed as ejection fraction (%) and plasma levels of NT-proBNP [ Time Frame: 1 year ]

    Left ventricular systolic function will be assessed by echocardiography and expressed as ejection fraction (%), as well as plasma levels of N-terminal prohormone of brain natriuretic peptide (NT-proBNP) (ng/L) measured at month 12.

    We will compare left ventricular ejection fraction and NT-proBNP plasma concentration at month 12 between patients who underwent extracorporeal photopheresis (ECP) to those who did not undergo extracorporeal photopheresis (ECP).


  6. Levels of T-lymphocyte subsets, B-lymphocytes, and NK cells in peripheral blood evaluated by the flow cytometry technique [ Time Frame: 1 year ]
    Peripheral blood samples will be taken just before transplantation, and then before 6th and 9th ECP cycle. Sample will be taken before leukapheresis and analyzed for WBC, hematocrit, mononuclear cells (MNC), and platelet counts. Number of T-lymphocyte subsets (CD3+, CD3+4+, CD3+8+, CD4+8+ ratio) B-lymphocytes (CD 19+), and NK cells (CD56+) in patient's peripheral blood will be taken according to schedule. The levels of T, B lymhocytes and NK cells will be evaluated by the flow cytometry technique (Becton Dickinson, Facs Calibur, USA). The values of lymphocyte subsets will be expressed as percentages and absolute counts (cells/μl).

  7. Number of patients with adverse events - safety assesments [ Time Frame: 1 year ]
    Safety will be assessed by the number of patients with adverse events including: death, all infections (pneumonia, CMV viremia/infection, urinary tract infection, wound infection, sepsis…), CMV viremia/infection, indwelling venous access catheters related bacteremia, indwelling venous access catheters related thrombosis. CMV will be documented as infection (viremia) and disease (viremia with clinical symptoms and signs).



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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age >18 and <65
  • primary orthotopic heart transplant
  • early photopheresis
  • adequate intravenous approach
  • signed informed consent

Exclusion Criteria:

  • aphakia
  • psoralen hypersensitivity
  • active retinal disease - photosensitive diseases
  • splenectomy
  • L <2000; Hb <70 g/L
  • coagulopathy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04226521


Contacts
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Contact: Boško Skorić 0953959910 ext +385 bskoric3@yahoo.com
Contact: Mia Dubravčić 989549898 ext +385 dubravcic.mia@gmail.com

Locations
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Croatia
UHC Zagreb Recruiting
Zagreb, Croatia, 10000
Contact: Davor Miličić    098471196 ext +385    predstojnik.skz@kbc-zagreb.hr   
Sponsors and Collaborators
Bosko Skoric
University of Zagreb
Investigators
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Principal Investigator: Boško Skorić UHC Zagreb

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Responsible Party: Bosko Skoric, Asst. prof., University of Zagreb
ClinicalTrials.gov Identifier: NCT04226521    
Other Study ID Numbers: ECP-OCT2019
First Posted: January 13, 2020    Key Record Dates
Last Update Posted: January 13, 2020
Last Verified: January 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: The data will be available in 2 years for time frame of 5 years

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Bosko Skoric, University of Zagreb:
Heart transplant
vasculopathy
extracorporeal photopheresis
prevention
optical coherence tomography
Additional relevant MeSH terms:
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Vascular Diseases
Cardiovascular Diseases