Clinical trial NCT02672683: Non Invasive Detection of Cardiac Allograft Rejection by Circulating microRNAs
Official title: Non Invasive Detection of Acute Rejection by Circulating microRNAs in Cardiac Transplantation: a Multicenter Prospective Study
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Cardiac Transplantation
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
First posted: 2016-02-03
Enrollment: 461
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with a cardiac transplant

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.

Eligibility criteria: 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

Primary outcomes:
measure: Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
timeFrame: one month
measure: Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
timeFrame: 3 months
measure: Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
timeFrame: 6 months
measure: Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
timeFrame: 12 months
Secondary outcomes:
measure: Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
timeFrame: 24 months
Other outcomes:
Locations:
city: Paris
country: France
facility: PARCC/ INSERM U970, Team 4, Xavier Jouven, Cardiovascular epidemiology and sudden death, Georges Pompidou European Hospital,
Study officials:
affiliation: Necker Hospital, AP-HP
name: Jean-paul Duong Van Huyen, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Duong Van Huyen JP, Tible M, Gay A, Guillemain R, Aubert O, Varnous S, Iserin F, Rouvier P, Francois A, Vernerey D, Loyer X, Leprince P, Empana JP, Bruneval P, Loupy A, Jouven X. MicroRNAs as non-invasive biomarkers of heart transplant rejection. Eur Heart J. 2014 Dec 1;35(45):3194-202. doi: 10.1093/eurheartj/ehu346. Epub 2014 Aug 31.