Clinical trial NCT04117152: Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation
Official title: Multicenter International Observational Study to Identify Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and Their Specific Determinants
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Transplantation
Allograft Arteriopathy
Lead sponsor: Paris Translational Research Center for Organ Transplantation
Sponsor class: OTHER
Collaborators: name: Groupe Hospitalier Pitie-Salpetriere
name: European Georges Pompidou Hospital
name: Universitaire Ziekenhuizen KU Leuven
name: Cedars-Sinai Medical Center
First posted: 2019-10-07
Enrollment: 1300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Heart recipients aged over 18 and of all genders recruited between 2004 and 2015 from European and North American centers, who had at least two coronary angiograms during follow-up.

Brief summary: This project aims: i) to identify Cardiac Allograft Vasculopathy (CAV) trajectories after heat transplantation using latent class mixed modeling, ii) to characterize the global and specific determinants of different trajectories and iii) to provide an easily accessible tool to project individual probability of CAV trajectory belonging.

Detailed description: Background:

Cardiac Allograft Vasculopathy (CAV) is the third cause of late mortality and the leading cause of late allograft dysfunction. The field of heart transplantation currently lacks longitudinal description of CAV profiles. Identifying relevant CAV trajectories, or evolution profiles, and their respective determinants is an unmet clinical need. CAV trajectories requires an additional level of understanding and characterization over the current paradigm. Understanding the mechanisms and clinical factors involved in the development of CAV will be useful to provide a more nuanced picture of disease progression, which may ultimately contribute to risk stratification and ultimately guiding the care of HTx patients.

Main Outcome(s) and Measure(s):

* Identification of CAV trajectories after transplantation using an unsupervised latent class mixed modeling. CAV angiograms were recorded per center protocol for all patients after transplantation. CAV was graded according to the current ISHLT classification as CAV 0 (not significant), 1 (mild), 2 (moderate) and 3 (severe).
* Determination of clinical, functional, structural, immunological factors associated with the trajectories. In the derivation cohort, the associations between CAV trajectories and clinical, histological, functional, and immunological parameters at the time of transplantation, during the first year and at one-year post-transplant were assessed using multinomial logistic regression.

Eligibility criteria: Inclusion Criteria:

* Heart recipient with at least two coronary angiograms after heart transplantation,
* Heart recipient over 18 years of age.

Exclusion Criteria:

* Patient with \< 2 coronary angiograms during follow-up

Primary outcomes:
measure: Identification of trajectories of Cardiac Allograft Vasculopathy (CAV)
timeFrame: 10 years post-transplant
Secondary outcomes:
measure: Identification of the specific determinants of CAV trajectories
timeFrame: From transplantation to 1-year post-transplant
measure: Early prediction of CAV trajectories
timeFrame: 10 years post-transplant
measure: Patients and allograft survival probability according the CAV trajectory
timeFrame: 10 years post-transplant
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Jon Kobashigawa
state: California
city: Leuven
country: Belgium
facility: Maarten Naesens
city: Paris
country: France
facility: Paris Transplant Group
Study officials:
affiliation: Paris Transplant Group
name: Alexandre Loupy, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Loupy A, Coutance G, Bonnet G, Van Keer J, Raynaud M, Aubert O, Bories MC, Racape M, Yoo D, Duong Van Huyen JP, Bruneval P, Taupin JL, Lefaucheur C, Varnous S, Leprince P, Guillemain R, Empana JP, Levine R, Naesens M, Patel JK, Jouven X, Kobashigawa J. Identification and Characterization of Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation: A Population-Based Study. Circulation. 2020 Jun 16;141(24):1954-1967. doi: 10.1161/CIRCULATIONAHA.119.044924. Epub 2020 May 4.