Coronary Artery Disease After Heart Transplantation

NCT03583229 | Unknown DMC

• 1 other identifier: ECP studiet
• Study Type: interventional
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

This study evaluates coronary artery disease after heart transplantation and its relation to platelet function. Furthermore, we will evaluate extracorporeal photopheresis as treatment of coronary artery disease after heart transplantation.

Conditions

Coronary Artery Disease in Transplanted Heart (Diagnosis); Platelet Dysfunction

Keywords

Heart Transplantation; Cardiac Allograft Vasculopathy

Outcome Measures

Primary Outcomes (1)

• Changes in CAV

  Changes in CAV assessed by CAG, OCT and advanced echocardiography

  Baseline and 12 months follow up

Secondary Outcomes (5)

• Platelet aggregation assessment related to CAV.

  Baseline and 7 days after aspirin treatment.

• Changes in platelet aggregation

  Baseline and 7 days after aspirin treatment.

• Changes in DSA levels

  Baseline and 12 months follow up

• Changes in exercise and longitudinal myocardial deformation capacity

  Baseline and 12 months follow up

• Changes in CFVR

  Baseline and 12 months follow up

Study Arms (3)

Aspirin - single arm

OTHER

1 tablet of Aspirin 75 mg administered x 1 daily for 7 days.

Drug: Aspirin 75mg

Extracorporeal photopheresis

EXPERIMENTAL

All patients with HLA antibodies receive 4 ECP-treatments in 2 months.

Drug: Aspirin 75mg; Other: Extracorporeal photopheresis

Control group

NO INTERVENTION

The control group does not receive ECP-treatments, but blood samples are drawn at the same intervals as treatment group and CAG+OCT are also performed at baseline and 12 months follow up as the treatment group.

Interventions

Aspirin 75mg DRUG

7 days treatment with 75 mg aspirin daily.

Aspirin - single arm; Extracorporeal photopheresis

Extracorporeal photopheresis OTHER

4 x ECP treatments in 60 days.

Extracorporeal photopheresis

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age 18-100
• Informed and signed consent
• Positive Luminex analysis: Blood samples with DSA levels \>3000 MFI
• Coronary angiography with evidence of CAV (ISHLT class ≥1) according to ISHLT criteria's.

You may not qualify if:

• Severe asthma or COLD with FEV1 \< 50%\*
• ° or 3° AV block\*
• Pregnancy
• Creatinine \>250 mmol/l\*\*
• Platelet count below 20 x 109/L
• History of allergy to 8-Methoxypsoralen (8-MOP)
• History of light-sensitive disease
• These patients will not be subjected to adenosine submission \*\*These patients will not be subjected to OCT evaluation
• Control groups:
• patients with angiographically proven coronary artery disease treated with 75 mg aspirin daily for at least seven days (no other antithrombotic drugs are allowed). These data is already available.
• healthy subjects on no medication - samples are taken before and after 75 mg aspirin daily for at least seven days. These data is already available.
• As the data regarding the control groups are already available from previous studies at our department, these control patients are no considered actively included in this study. Hence, the patient population consists of the 60 HTx patients.

Sponsors & Collaborators

• Aarhus University Hospital: lead

Study Sites (1)

Aarhus Universitetshospital, Afdeling for Hjertesygdomme

Aarhus N, 8200, Denmark

RECRUITING

Related Publications (13)

• Clemmensen TS, Munk K, Tram EM, Ilkjaer LB, Severinsen IK, Eiskjaer H. Twenty years' experience at the Heart Transplant Center, Aarhus University Hospital, Skejby, Denmark. Scand Cardiovasc J. 2013 Dec;47(6):322-8. doi: 10.3109/14017431.2013.845688. Epub 2013 Oct 16.

  PMID: 24131212 BACKGROUND

• Stehlik J, Edwards LB, Kucheryavaya AY, Benden C, Christie JD, Dipchand AI, Dobbels F, Kirk R, Rahmel AO, Hertz MI; International Society of Heart and Lung Transplantation. The Registry of the International Society for Heart and Lung Transplantation: 29th official adult heart transplant report--2012. J Heart Lung Transplant. 2012 Oct;31(10):1052-64. doi: 10.1016/j.healun.2012.08.002. No abstract available.

  PMID: 22975095 BACKGROUND

• Berry GJ, Burke MM, Andersen C, Bruneval P, Fedrigo M, Fishbein MC, Goddard M, Hammond EH, Leone O, Marboe C, Miller D, Neil D, Rassl D, Revelo MP, Rice A, Rene Rodriguez E, Stewart S, Tan CD, Winters GL, West L, Mehra MR, Angelini A. The 2013 International Society for Heart and Lung Transplantation Working Formulation for the standardization of nomenclature in the pathologic diagnosis of antibody-mediated rejection in heart transplantation. J Heart Lung Transplant. 2013 Dec;32(12):1147-62. doi: 10.1016/j.healun.2013.08.011.

  PMID: 24263017 BACKGROUND

• Patel J, Klapper E, Shafi H, Kobashigawa JA. Extracorporeal photopheresis in heart transplant rejection. Transfus Apher Sci. 2015 Apr;52(2):167-70. doi: 10.1016/j.transci.2015.02.004. Epub 2015 Feb 11.

  PMID: 25748232 BACKGROUND

• Barten MJ, Dieterlen MT. Extracorporeal photopheresis after heart transplantation. Immunotherapy. 2014;6(8):927-44. doi: 10.2217/imt.14.69.

  PMID: 25313571 BACKGROUND

• Matsuo Y, Cassar A, Li J, Flammer AJ, Choi BJ, Herrmann J, Gulati R, Lennon RJ, Kang SJ, Maehara A, Kitabata H, Akasaka T, Lerman LO, Kushwaha SS, Lerman A. Repeated episodes of thrombosis as a potential mechanism of plaque progression in cardiac allograft vasculopathy. Eur Heart J. 2013 Oct;34(37):2905-15. doi: 10.1093/eurheartj/eht209. Epub 2013 Jun 19.

  PMID: 23782648 BACKGROUND

• Cassar A, Matsuo Y, Herrmann J, Li J, Lennon RJ, Gulati R, Lerman LO, Kushwaha SS, Lerman A. Coronary atherosclerosis with vulnerable plaque and complicated lesions in transplant recipients: new insight into cardiac allograft vasculopathy by optical coherence tomography. Eur Heart J. 2013 Sep;34(33):2610-7. doi: 10.1093/eurheartj/eht236. Epub 2013 Jun 25.

  PMID: 23801824 BACKGROUND

• Arbustini E, Dal Bello B, Morbini P, Gavazzi A, Specchia G, Vigano M. Multiple coronary thrombosis and allograft vascular disease. Transplant Proc. 1998 Aug;30(5):1922-4. doi: 10.1016/s0041-1345(98)00526-0. No abstract available.

  PMID: 9723334 BACKGROUND

• Modjeski KL, Morrell CN. Small cells, big effects: the role of platelets in transplant vasculopathy. J Thromb Thrombolysis. 2014 Jan;37(1):17-23. doi: 10.1007/s11239-013-0999-4.

  PMID: 24264961 BACKGROUND

• Maeda A. Extracorporeal photochemotherapy. J Dermatol Sci. 2009 Jun;54(3):150-6. doi: 10.1016/j.jdermsci.2009.03.002. Epub 2009 Apr 14.

  PMID: 19369039 BACKGROUND

• Ward DM. Extracorporeal photopheresis: how, when, and why. J Clin Apher. 2011;26(5):276-85. doi: 10.1002/jca.20300. Epub 2011 Sep 5.

  PMID: 21898572 BACKGROUND

• Lu WH, Palatnik K, Fishbein GA, Lai C, Levi DS, Perens G, Alejos J, Kobashigawa J, Fishbein MC. Diverse morphologic manifestations of cardiac allograft vasculopathy: a pathologic study of 64 allograft hearts. J Heart Lung Transplant. 2011 Sep;30(9):1044-50. doi: 10.1016/j.healun.2011.04.008. Epub 2011 Jun 2.

  PMID: 21640617 BACKGROUND

• Gould KL, Lipscomb K. Effects of coronary stenoses on coronary flow reserve and resistance. Am J Cardiol. 1974 Jul;34(1):48-55. doi: 10.1016/0002-9149(74)90092-7. No abstract available.

  PMID: 4835753 BACKGROUND

MeSH Terms

Conditions

Disease

Interventions

Aspirin; Photopheresis

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Salicylates; Hydroxybenzoates; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; PUVA Therapy; Ultraviolet Therapy; Phototherapy; Therapeutics; Extracorporeal Circulation; Surgical Procedures, Operative

Study Officials

• Hans Eiskjær, Professor

  Aarhus Universitetshospital, Afdeling for Hjertesygdomme, Palle Juul Jensens Blvd. 99, 8200 Aarhus N

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kamilla Pernille Bjerre, MD

CONTACT

0045 53535832; kambje@rm.dk

Hans Eiskjær, Professor

CONTACT

0045 30922347; hanseisk@rm.dk

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, DMSc

Model Details: Patients with antibodies receive 4 ECP-treatments if they have CAV. If patients do not want to receive ECP-treatments, they are allocated to the control group, which do not receive ECP-treatments. All patients receive 7 days treatment with aspirin and blood samples are drawn before and after.

Study Record Dates

• First Submitted: June 27, 2018
• First Posted: July 11, 2018
• Study Start: October 13, 2016
• Primary Completion: October 1, 2021
• Study Completion: October 1, 2021
• Last Updated: February 7, 2020

Record last verified: 2020-02

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)