Mitral Valve DiseaseMAD-NesSNCT04916535
Prospective Multicenter Study on Mitral Annular Disjunction
A study testing diagnostic flow in people with Mitral Valve Disease, run by University Hospital of Ferrara at 7 sites in Italy.
Trial summary
Observational cohort prospective multicenter study on patients with mitral annular disjunction (MAD). MAD is defined as a separation (≥1 mm) between the atrial wall-mitral valvular junction and the left ventricular free wall during end-systole Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Mitral Valve Disease
- What is being tested?
- diagnostic flow
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 249 participants
- Where
- 7 sitesItaly
- Study dates
- 3 Jun 2021to 1 Jul 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject aged ≥18 years and <65 years
- Evidence of MAD during routine echocardiography clinically indicated by treating physician for any reason
- Written informed consent
Who cannot join
- Patient's refusal
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
Italy7 sites
Cardiology Unit
Bologna
University Hospital of Ferrara
Ferrara, Ferrara, 44124
Morgagni Hospital
Forlì
Cardiology Unit
Palermo
Santa Maria delle Croci Hospital
Ravenna
Cardiology Unit
Rimini
University Hospital fo Trieste
Trieste
About this study
Official title: Observational Cohort Prospective Multicenter Study on Mitral Annular Disjunction (MAD) - MAD multiceNter Study (MAD-NesS)
Observational cohort prospective multicenter study on patients with mitral annular disjunction (MAD). MAD is defined as a separation (≥1 mm) between the atrial wall-mitral valvular junction and the left ventricular free wall during end-systole
Read the detailed description
Mitral annular disjunction (MAD) is a structural abnormality of the mitral annulus, defined as a separation (≥1 mm) between the atrial wall-mitral valvular junction and the left ventricular free wall during end-systole. This abnormality is significantly associated with the presence of mitral valve prolapse (MVP), but it can also be observed in normal hearts. MAD-related hypermobility of the mitral apparatus and the consequent posterior systolic curling determine a mechanical stress of the infero-basal wall and papillary muscle. This phenomenon leads to myocardial hypertrophy and fibrosis, creating an arrhythmogenic substrate and a source of electrical instability. For this reason, the analysis of left ventricle by cardiac magnetic resonance plays a pivotal role in the identification of predictors of fatal arrhythmic events, such as sudden cardiac death (SCD). Taking into account that MAD could be present without MVP, some studies analyzed the association between MAD and arrhythmic events. They showed that MAD itself is a risk marker of electrical instability supporting the existence of an emerging clinical entity: the MAD arrhythmic syndrome. An in deep analysis of MAD patients and their characteristics in terms of EKG, types of arrhythmia, echocardiographic parameters and cardiac magnetic resonance (CMR) data and long-term events is lacking.
The present study is ideated and conducted to fill this gap and collect information regarding management and outcome of patients with MAD
- Conditions
- Mitral Valve Disease
- Being tested
- diagnostic flow
- Keywords
- mitral annular disjunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
diagnostic flowOther
exams to estimate the risk of adverse events in patients with MAD
| Study group | Role | What they receive |
|---|---|---|
| diagnostic flow | Experimental | all patients with MAD as assessed during routine transthoracic echocardiography will undergo to the following further exams: i) 12-lead electrocardiogram (ECG), ii) 24-hour ECG monitoring, iii) cardiac magnetic resonance imaging (CMR), iv) cardiological visit Receives: Other: diagnostic flow |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pathological findings associated with MAD
Percentage of subjects with MAD whom deeper analysis with cardiological visit, electrocardiogram (ECG), 24-hour ECG Holter monitoring and cardiac magnetic resonance (CMR) identifies pathological findings. Pathological findings are defined as follows: -T wave inversion in inferolateral leads at ECG
- frequent premature ventricular complexes (>1000/24h)
- non-sustained ventricular arrythmias
- sustained ventricular arrythmias
- severe mitral regurgitation
- myocardial fibrosis with a non-ischemic pattern, especially of papillary muscles and inferolateral wall. The primary endpoint will be considered achieved if at least one of the above mentioned paramentrs will be found in the patient
Measured: 3 months
Secondary outcomes (4)
surgery for mitral valve
occurrence of mitral surgery
Measured: 5 years
sudden cardiac death
occurrence of sudden cardiac death
Measured: 5 years
aborted cardiac arrest
occurrence of aborted cardiac arrest
Measured: 5 years
ventricular arrhythmia
occurrence of non-sustained and/or sustained ventricular tachycardia
Measured: 5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Jun 2021
- Study start3 Jun 2021
- Primary completion1 Jul 2025
- Study completion1 Jul 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Mitral Valve DiseaseStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Observational cohort prospective multicenter study on patients with MAD
- Masking
- None (open label)
- Enrolment
- 249 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital of Ferrara
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Gianluca Campo, University Hospital of Ferrara
- Investigators
- Elisabetta Tonet, MD, Principal investigator, University Hospital of Ferrara
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04916535
- Sponsor's protocol ID
- 367/2021/Oss/AOUFe
- Acronym
- MAD-NesS
- Status last verified
- Jul 2025
- First submitted
- 3 Jun 2021
- Last updated
- 15 Jul 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Observational Cohort Prospective Multicenter Study on Mitral Annular Disjunction (MAD) - MAD multiceNter Study (MAD-NesS)
- ClinicalTrials.gov ID
- NCT04916535
- Acronym / sponsor ID
- MAD-NesS / 367/2021/Oss/AOUFe
- Conditions
- Mitral Valve Disease
- Keywords
- mitral annular disjunction
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 249 participants (actual)
- Lead sponsor
- University Hospital of FerraraUniversity, hospital or other
- Study start
- 3 Jun 2021 (actual)
- Primary completion
- 1 Jul 2025 (actual)
- Study completion
- 1 Jul 2030 (estimated)
- First posted
- 7 Jun 2021 (actual)
- 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.
Observational cohort prospective multicenter study on patients with mitral annular disjunction (MAD). MAD is defined as a separation (≥1 mm) between the atrial wall-mitral valvular junction and the left ventricular free wall during end-systole
Detailed description
Mitral annular disjunction (MAD) is a structural abnormality of the mitral annulus, defined as a separation (≥1 mm) between the atrial wall-mitral valvular junction and the left ventricular free wall during end-systole. This abnormality is significantly associated with the presence of mitral valve prolapse (MVP), but it can also be observed in normal hearts. MAD-related hypermobility of the mitral apparatus and the consequent posterior systolic curling determine a mechanical stress of the infero-basal wall and papillary muscle. This phenomenon leads to myocardial hypertrophy and fibrosis, creating an arrhythmogenic substrate and a source of electrical instability. For this reason, the analysis of left ventricle by cardiac magnetic resonance plays a pivotal role in the identification of predictors of fatal arrhythmic events, such as sudden cardiac death (SCD). Taking into account that MAD could be present without MVP, some studies analyzed the association between MAD and arrhythmic events. They showed that MAD itself is a risk marker of electrical instability supporting the existence of an emerging clinical entity: the MAD arrhythmic syndrome. An in deep analysis of MAD patients and their characteristics in terms of EKG, types of arrhythmia, echocardiographic parameters and cardiac magnetic resonance (CMR) data and long-term events is lacking.
The present study is ideated and conducted to fill this gap and collect information regarding management and outcome of patients with MAD
Study design
- Primary purpose
- Other
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Observational cohort prospective multicenter study on patients with MAD
| Arm | Type | Receives |
|---|---|---|
| diagnostic flow | Experimental | Other: diagnostic flowall patients with MAD as assessed during routine transthoracic echocardiography will undergo to the following further exams: i) 12-lead electrocardiogram (ECG), ii) 24-hour ECG monitoring, iii) cardiac magnetic resonance imaging (CMR), iv) cardiological visit |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Subject aged ≥18 years and <65 years
- Evidence of MAD during routine echocardiography clinically indicated by treating physician for any reason
- Written informed consent
Key exclusion criteria (1 listed)
- Patient's refusal
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| diagnostic flowexams to estimate the risk of adverse events in patients with MAD | Other | diagnostic flow |
Primary outcome
Pathological findings associated with MAD
Time frame: 3 months
Percentage of subjects with MAD whom deeper analysis with cardiological visit, electrocardiogram (ECG), 24-hour ECG Holter monitoring and cardiac magnetic resonance (CMR) identifies pathological findings. Pathological findings are defined as follows: -T wave inversion in inferolateral leads at ECG * frequent premature ventricular complexes (>1000/24h) * non-sustained ventricular arrythmias * sustained ventricular arrythmias * severe mitral regurgitation * myocardial fibrosis with a non-ischemic pattern, especially of papillary muscles and inferolateral wall. The primary endpoint will be considered achieved if at least one of the above mentioned paramentrs will be found in the patient
4 secondary outcomes
surgery for mitral valve
Time frame: 5 years
sudden cardiac death
Time frame: 5 years
aborted cardiac arrest
Time frame: 5 years
ventricular arrhythmia
Time frame: 5 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2025.
- Individual participant dataSharing planned: Undecided
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Recruiting
LEFT ATRIAL MONITORING IN PATIENTS BEFORE AND AFTER MITRAL SURGERY - LAMBDA STUDY
Mitral Regurgitation, Mitral Valve Disease
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Multi-center Study of Three-Dimensional Transesophageal Echocardiography in Patients With Secondary Mitral Regurgitation
Mitral Valve Insufficiency
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Early Feasibility Study of the Capstan Medical TMVR System
Mitral Regurgitation (MR)
Not yet recruitingObservational study
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Aortic Stenosis, Mitral Regurgitation
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.
Elisabetta Tonet, MD principal investigator
University Hospital of Ferrara
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing diagnostic flow in people with Mitral Valve Disease, run by University Hospital of Ferrara at 7 sites in Italy.
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 3 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: under way, not looking for participants, as of the sponsor's last update on 15 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in Italy. 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?
This study is still under way. Results are not available in the source record yet.
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?
Pathological findings associated with MAD (time frame: 3 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 15 Jul 2025.