Detection of Acute Graft Rejection in Heart Transplant Patients by Estimation of T2 (DRAGET)

"Detection of Acute Rejection in Heart Transplant Patients by Mean of T2 Quantification With MRI" Open Transversal Clinical Trial With Repeated Measures

The investigators propose a simple and non-invasive method to monitor heart transplant patients with MRI. Its diagnostic and prognostic values have already been assessed in two monocentric studies. Other monocentric studies based on related methods have confirmed the investigators findings. These studies are insufficient to allow a large diffusion of the technique. Only a large multi-centric study will change medical practices. In addition, this project will spread the new method at a national level and will allow an assessment of its practical usefulness in centres not familiar with MRI T2 quantification.

Furthermore, MRI seems to detect rejections at earlier stage than biopsy. A confirmation of this observation could lead to a modification of diagnostic criteria of cardiac graft rejection. The ultimate aim of the DRAGET project is to replace a strategy based solely on biopsy with one based on a first-line MRI (with biopsy only when needed) for a more efficient and earlier detection of rejection. This would constitute a major advance in patients security and comfort as well as an economic improvement.

Study Overview

• Status: Completed
• Conditions: Heart Transplantation; Acute Graft Rejection
• Intervention / Treatment: Device: MRI T2 quantification

• Study Type: Interventional
• Enrollment (Actual): 116
• Phase: Not Applicable

Contacts and Locations

Study Locations

• France
  • Bron, France, 69677
    • Hospices Civils de Lyon
  • La Tronche, France, 38700
    • CHU Grenoble
  • Nancy, France
    • Chru Nancy Brabois
  • Nantes, France, 44093
    • CHU de Nantes
  • Paris, France, 75015
    • Hopital Europeen Georges Pompidou
  • Paris, France, 75651
    • Groupe Hospitalier Pitie-Salpetriere
  • Pessac, France, 33604
    • CHU Bordeaux
  • Rennes, France, 35033
    • Chu de Rennes
  • Strasbourg, France
    • Hôpitaux Universitaires de Strasbourg
  • Tours, France, 37044
    • CHU de Tours

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Heart transplant patient
• Able to realize 4 couples Biopsy/MRI within 12 months after the transplant
• Mandatory enrolment in a social security plan
• Patient having signed an informed consent.

Exclusion Criteria:

• Contraindication to MRI: pacemaker, ferromagnetic foreign body, etc
• Impossibility to undergo MRI: claustrophobia, morbid obesity, hospitalisation in intensive care unit, arrhythmia
• Pregnancy
• Patients under a measure of legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: ALL_patients; MRI T2 quantification : heart transplant patients will have 4-6 MRI exams for T2 quantification during their first year after transplantation.

Device: MRI T2 quantification; MRI acquisitions will be performed according to the already described method based on conventional Fast Spin Echo sequences and with an additional calibration pad positioned on the patient thorax (dedicated pad made by the Nancy CIC-IT with stable and adapted T2). MRI will be performed if possible before the biopsy and otherwise the radiologist will be kept blinded of the biopsy results.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sensitivity and specificity of myocardial T2 assessed with MRI for the diagnosis of histological heart graft rejection (with 95% confidence interval).	endpoint = sensitivity and specificity acute rejection means presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R)	3 years after first inclusion

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of histological or clinical rejection within months of a couple MRI/biopsy with normal biopsy (grade<2R).	endpoint = number of rejections For this purpose, rejection will be defined as: a) acute rejection documented by presence of damaged myocytes in endomyocardial biopsy (former grade 2, grade 2R and grade 3R), or b) marked decrease in left ventricle ejection fraction (>10%), reversible after subsequent increase in immunosuppressive treatment.	3 years after first inclusion
Complications with MRI and with biopsies.	endpoint = Number of adverse events due to both exams	3 years after first inclusion
Magnitude of better tolerability of MRI over biopsies for the patient.	endpoint = Physical and psychological distress assessed by questionnaire using Likert scales. This questionnaire will be completed by the patients.	3 years after first inclusion
Inter-observer reproducibility of T2 quantification with MRI and of pathological grading of the biopsies.	endpoint = 95% interobserver limit of agreement for T2 quantification and Cohen's Kappa coefficient for histological grading.	3 years after first inclusion
Level of confidence, at the end of the study, of the expert-physicians of each centre concerning the use of T2 quantification as an alternative to routine biopsies.	endpoint = Confidence assessed by questionnaire using Likert scales. This questionnaire will be completed by study investigators at the end of the study.	3 years after first inclusion

Collaborators and Investigators

• Sponsor: Central Hospital, Nancy, France
• Investigators: Principal Investigator: Laurent Bonnemains, MD, PhD, INSERM, IADI U47, Nancy, France

Publications and helpful links

General Publications

• Bonnemains L, Cherifi A, Girerd N, Odille F, Felblinger J. Design of the DRAGET Study: a multicentre controlled diagnostic study to assess the detection of acute rejection in patients with heart transplant by means of T2 quantification with MRI in comparison to myocardial biopsies. BMJ Open. 2015 Oct 29;5(10):e008963. doi: 10.1136/bmjopen-2015-008963.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2015
• Primary Completion (Actual): February 27, 2020
• Study Completion (Actual): February 27, 2020

Study Registration Dates

• First Submitted: September 25, 2014
• First Submitted That Met QC Criteria: October 9, 2014
• First Posted (Estimate): October 10, 2014

Study Record Updates

• Last Update Posted (Actual): May 12, 2020
• Last Update Submitted That Met QC Criteria: May 11, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: MRI, T2 quantification
• Other Study ID Numbers: 2014-A00848-39; CIC1433 (Other Identifier: 12-109_DRAGET)