Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation (TRAJ-CAV)

Multicenter International Observational Study to Identify Trajectories of Cardiac Allograft Vasculopathy After Heart Transplantation and Their Specific Determinants

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.

Study Overview

• Status: Completed
• Conditions: Heart Transplantation; Allograft Arteriopathy
• Intervention / Treatment: Other: Latent class mixed modeling

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.

• Study Type: Observational
• Enrollment (Actual): 1300

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium
    • Maarten Naesens
• France
  • Paris, France, 75015
    • Paris Transplant Group
• United States
  • California
    • Los Angeles, California, United States, 90211
      • Jon Kobashigawa

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• 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.

Description

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

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of trajectories of Cardiac Allograft Vasculopathy (CAV)	Identification of different evolutive profiles of CAV using latent classes mixed models. Each coronary angiogram was graded from 0 (no CAV) to 3 (severe CAV) according to ISHLT classification.	10 years post-transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of the specific determinants of CAV trajectories	Identification of immune and non-immune determinants using multivariable multinomial logistic regression.	From transplantation to 1-year post-transplant
Early prediction of CAV trajectories	Probability of belonging to each trajectory according to the baseline angiogram and independent risk factors for CAV	10 years post-transplant
Patients and allograft survival probability according the CAV trajectory	Comparison of prognosis according the CAV trajectory	10 years post-transplant

Collaborators and Investigators

• Sponsor: Paris Translational Research Center for Organ Transplantation
• Collaborators: Universitaire Ziekenhuizen KU Leuven; Cedars-Sinai Medical Center; Groupe Hospitalier Pitie-Salpetriere; European Georges Pompidou Hospital
• Investigators: Principal Investigator: Alexandre Loupy, MD, PhD, Paris Transplant Group

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2004
• Primary Completion (Actual): May 1, 2020
• Study Completion (Actual): June 1, 2020

Study Registration Dates

• First Submitted: October 3, 2019
• First Submitted That Met QC Criteria: October 4, 2019
• First Posted (Actual): October 7, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2020
• Last Update Submitted That Met QC Criteria: September 14, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases
• Other Study ID Numbers: ParisTRCOT_CAV

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No