Non Invasive Detection of Cardiac Allograft Rejection by Circulating microRNAs

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

Status

Completed

Phases

Unknown

Study type

Observational

Source

ClinicalTrials.gov

Registry ID

NCT02672683

Acronym

MIRRACLE

Enrollment

461

Registered

2016-02-03

Start date

2016-09-26

Completion date

2019-03-26

Last updated

2025-11-20

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Cardiac Transplantation

Brief summary

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.

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.

Interventions

None listed

Study design

Observational model

COHORT

Time perspective

PROSPECTIVE

Eligibility

Sex/Gender

ALL

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy	one month

Secondary

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

Countries

France

Outcome results