Non Invasive Detection of Cardiac Allograft Rejection by Circulating microRNAs (MIRRACLE)

November 17, 2025 updated by: Assistance Publique - Hôpitaux de Paris

Non Invasive Detection of Acute Rejection by Circulating microRNAs in Cardiac Transplantation: a Multicenter Prospective Study

The purpose of this study is to evaluate the level of expression of 4 circulating microRNAs in the serum using RT-PCR. A pilote study with cardiac transplant patients has shown that expression of these microRNAs could discriminate patients with a histologically proven rejection from patient displaying a normal endomyocardial biopsy. The signature must be confirmed in unselected patients and its stability evaluated according to clinical, biological and immunological parameters of included patients.

Study Overview

Status

Completed

Conditions

Detailed Description

Heart transplantation is the only available long-term treatment option for patients with terminal heart failure.

Despite considerable progress in immunosuppressive regimens, allograft rejection remains a major cause of graft loss.

Majority of cardiac allograft rejection are asymptomatic. Only severe rejection goes along with cardiac dysfunction. This clinical latency makes the cardiac rejection diagnostic difficult and has ruled modalities of detection of cardiac rejection.

The cornerstone of rejection diagnosis and post-transplant follow-up relies on endomyocardial biopsy (EMB) and classical histopathology assessment. Echocardiography and MRI are neither sensitive nor specific enough to replace EMB. Majority of transplant centers thus evaluate rejection using iterative protocol biopsies. These cardiac allograft monitoring protocols are heavy, with 15 to 20 EMB in the first year of transplantation and 1 to 2 EMB each year after the first year. EMB are invasive procedure with a low but not zero risk of severe adverse events. Repetition of EMB is associated with tricuspid regurgitation due to valvular complications. Moreover incidence of cardiac rejection explains the cost-effectiveness of EMBs: 50 to 70% of biopsies are normal.

The goal is thus to detect rejection in the blood by measuring expression levels of 4 circulating microRNAs in patients' sera by RT-PCR. The seric expression levels of these 4 circulating microRNAs will be compared to the histopathological diagnosis made on concomitant endomyocardial biopsy.

Study Type

Observational

Enrollment (Actual)

461

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Paris, France, 75015
        • PARCC/ INSERM U970, Team 4, Xavier Jouven, Cardiovascular epidemiology and sudden death, Georges Pompidou European Hospital,

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Patients with a cardiac transplant

Description

Inclusion Criteria:

  • Patients with a cardiac transplant at the time of inclusion
  • Patients transplanted for less than 10 years and having an annual follow-up
  • Patients with a biopsy evaluation during their follow-up, at month 1, 3, 6, 12 (newly transplanted) and annually (newly and already transplanted patients) and concomitant routine blood work
  • Patients not opposed to the study
  • Patients with assessment of anti-donor specific antibodies during the study period

Exclusion Criteria:

  • Patients with a multi-organ transplantation

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time Frame: one month
one month
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time Frame: 3 months
3 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time Frame: 6 months
6 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time Frame: 12 months
12 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time Frame: 24 months
24 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assistance Publique - Hôpitaux de Paris

Collaborators

URC-CIC Paris Descartes Necker Cochin

Investigators

  • Principal Investigator: Jean-paul Duong Van Huyen, MD, PhD, Necker Hospital, AP-HP

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 26, 2016

Primary Completion (Actual)

April 20, 2017

Study Completion (Actual)

March 26, 2019

Study Registration Dates

First Submitted

November 30, 2015

First Submitted That Met QC Criteria

January 29, 2016

First Posted (Estimated)

February 3, 2016

Study Record Updates

Last Update Posted (Actual)

November 20, 2025

Last Update Submitted That Met QC Criteria

November 17, 2025

Last Verified

November 1, 2025

More Information

Terms related to this study

Other Study ID Numbers

  • AOR 14086

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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