Cardiac TransplantationMIRRACLENCT02672683
Non Invasive Detection of Cardiac Allograft Rejection by Circulating microRNAs
An observational study of Cardiac Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial 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… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Cardiac Transplantation
- How many people
- 461 participants
- Where
- 1 siteFrance
- Study dates
- 26 Sep 2016to 26 Mar 2019
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Patients with a cardiac transplant
Who may be able to join
- 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
Who cannot join
- Patients with a multi-organ transplantation
Trial locations and contacts
1 site in 1 country.
France1 site
PARCC/ INSERM U970, Team 4, Xavier Jouven, Cardiovascular epidemiology and sudden death, Georges Pompidou European Hospital,
Paris, 75015
About this study
Official title: 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.
Read the 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.
- Conditions
- Cardiac Transplantation
What is being measured
The primary outcome is the main question the study is designed to answer.
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Measured: one month
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Measured: 3 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Measured: 6 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Measured: 12 months
Secondary outcomes (1)
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Measured: 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Feb 2016 (estimated)
- Study start26 Sep 2016
- Primary completion20 Apr 2017
- Study completion26 Mar 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cardiac TransplantationStudies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 461 participants (actual)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Responsible party
- Sponsor
- Investigators
- Jean-paul Duong Van Huyen, MD, PhD, Principal investigator, Necker Hospital, AP-HP
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02672683
- Sponsor's protocol ID
- AOR 14086
- Acronym
- MIRRACLE
- Status last verified
- Nov 2025
- First submitted
- 30 Nov 2015
- Last updated
- 20 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
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.
PubMed 25176944Coutance G, Racape M, Baudry G, Lecuyer L, Roubille F, Blanchart K, Epailly E, Vermes E, Pattier S, Boignard A, Gay A, Bruneval P, Jouven X, Duong Van Huyen JP, Loupy A. Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study. J Heart Lung Transplant. 2023 Nov;42(11):1505-1509. doi: 10.1016/j.healun.2023.07.010. Epub 2023 Jul 23.
PubMed 37487804
Study at a glance
From the registry record, last updated by the sponsor on 20 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Non Invasive Detection of Acute Rejection by Circulating microRNAs in Cardiac Transplantation: a Multicenter Prospective Study
- ClinicalTrials.gov ID
- NCT02672683
- Acronym / sponsor ID
- MIRRACLE / AOR 14086
- Conditions
- Cardiac Transplantation
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 461 participants (actual)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Collaborators
- URC-CIC Paris Descartes Necker Cochin
- Study start
- 26 Sep 2016 (actual)
- Primary completion
- 20 Apr 2017 (actual)
- Study completion
- 26 Mar 2019 (actual)
- First posted
- 3 Feb 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Patients with a cardiac transplant
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- Patients with a multi-organ transplantation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time frame: one month
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time frame: 3 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time frame: 6 months
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time frame: 12 months
1 secondary outcome
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy
Time frame: 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Nov 2025.
- Background: PubMed 25176944Duong 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.
- Results publication: PubMed 37487804Coutance G, Racape M, Baudry G, Lecuyer L, Roubille F, Blanchart K, Epailly E, Vermes E, Pattier S, Boignard A, Gay A, Bruneval P, Jouven X, Duong Van Huyen JP, Loupy A. Validation of the clinical utility of microRNA as noninvasive biomarkers of cardiac allograft rejection: A prospective longitudinal multicenter study. J Heart Lung Transplant. 2023 Nov;42(11):1505-1509. doi: 10.1016/j.healun.2023.07.010. Epub 2023 Jul 23.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-paul Duong Van Huyen, MD, PhD principal investigator
Necker Hospital, AP-HP
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Transplantation, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 20 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Comparison of circulating MicroRNAs measurement in serum with histopathological diagnosis of rejection on concomitant endomyocardial biopsy (time frame: one month). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02672683, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Nov 2025.