Mitral Insufficiency, Mitral Regurgitation
Conditions
Keywords
mitral valve, mitral surgery, mitral repair, mitral annuloplasty, mitral valve surgery, mitral valve repair, mitral valve annuloplasty
Brief summary
The purpose of the trial is to demonstrate the safety and performance of the Medtentia Annuloplasty Ring (MAR) during mitral valve repair surgery. In addition, the trial aims to demonstrate that the MAR fulfills the requirements for mitral valve annuloplasty rings.
Detailed description
The purpose of this study is to evaluate the safety and performance of the MAR in patients with mitral regurgitation requiring either isolated mitral valve annuloplasty or mitral valve annuloplasty concomitantly with any of the following, either individually or in combination: * Tricuspid valve repair * Coronary artery bypass grafting (CABG) * Valve resection and chordae repair * Correction of atrial septal defect * Correction of patent foramen ovale * Ablation therapy for atrial defibrillation
Interventions
DEVICEMitral valve repair using the Medtentia Annuloplasty Ring (MAR)
Sponsors
Medtentia International Ltd Oy
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Prospective, multi-national, multi-center, open-label, single-arm
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
No
Inclusion criteria
Eligible patients must meet all the following inclusion criteria: 1. Signed Informed Consent Form. 2. Male or female aged ≥18 to ≤ 85 years on the day of screening. Females of childbearing potential (not surgically sterilized or more than one year post-menopausal) must have a negative pregnancy test (serum beta-human chorionic gonadotropin (beta-hCG) or urine) within 24 hours prior to mitral valve surgery. 3. Patient must meet one of the following indications for mitral repair surgery according to the European Society of Cardiology (ESC) and the American Heart Association (AHA) guidelines, and must have consented to have such surgery before undergoing the informed consent process for this study. * Symptomatic patient with chronic severe primary mitral regurgitation (MR), left ventricle ejection fraction (LVEF) \> 30% and left ventricle end systolic diameter (LVESD) \< 55 mm or * Asymptomatic patient with chronic severe primary MR who either: * Has LV dysfunction (LVEF ≤ 60 % and/or LVESD ≥ 40 mm or * Has a preserved LV function (LVEF\> 60% and LVESD \< 40 mm) together with a likelihood of a successful and durable repair of \> 95 % and an expected mortality rate of \< 1% or * Has a flail leaflet and LVESD ≥ 40 mm together with a high likelihood of durable repair and a low surgical risk or * Has a new onset of atrial fibrillation or pulmonary hypertension (systolic pulmonary pressure \> 50 mm Hg at rest) or * Asymptomatic patient with chronic moderate or severe primary MR who is to undergo cardiac surgery for another indication when the mitral valve (MV) repair can be performed concomitantly * Patient with chronic severe or moderate secondary MR and an LVEF \> 30 % who is undergoing CABG concomitantly 4. Patient must have a life expectancy of more than 24 months at the time of screening, assuming they undergo mitral valve annuloplasty. 5. Patient must have a mitral valve diameter corresponding to MAR size 26 - 40 and leaflet thickness (smallest helix height - largest helix height) for which an appropriate MAR ring is available. 6. Patient must be able and willing to attend all scheduled visits and comply with all study procedures.
Exclusion criteria
Eligible patients must not meet any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety: All-cause Mortality Occurring in the Time From Surgery Through Hospital Discharge. | Time from surgery through hospital discharge, up to 7 days. | — |
| Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes From Baseline (SC) to Three Months (V03) as Measured by Trans-thoracic Echocardiography (TTE). | Time from baseline through V03 (3 months) | Success will be defined as an improvement in at least 2 degrees in mitral regurgitation (MR) class as described in the ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (Bonow, et al., 2008). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Safety: The Occurrence, Nature and Frequency of Treatment-emergent Adverse Events (AEs), in Particular Severe Serious Adverse Device Effects (SADEs). | From surgery to end of study (2 years). | All the adverse events reported were non-device related. |
| Safety: The Occurrence, Nature and Frequency of Device Deficiencies and Adverse Device Effects (ADEs). | From surgery to end of study (2 years). | — |
| Safety: The Occurrence, Frequency and Nature of Abnormalities in the Period From Surgery Through Follow-up (Detailed List in Description Field). | From surgery to end of study (2 years). | The occurrence, frequency and nature of abnormalities in any of the following: * physical examination * vital signs * electrocardiography (ECG) * echocardiography (ECHO) * Laboratory tests * Chest X-rays (taken only when clinically indicated) |
| Performance: Mitral Regurgitation (MR) as Seen in Trans-esophageal Echocardiography (TEE) Performed During Surgery Before and After Annuloplasty. | Day of surgery visit (V01). | Success will be defined as no or only residual mitral regurgitation (MR). |
| Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes at Each Follow-up Visit (V04-V06) of the Improvement in MR From Screening, as Measured by Trans-thoracic Echocardiography (TTE). | V06 (24 months) | Measurement analysis at 24 months after successful MAR implantation. |
| Safety: 30-day Mortality and Mortality at 3 Months, 6 Months, 1 Year, 1.5 Years and 2 Years. | 30 days, 3 months, 6 months, 1 year, 1.5 years and 2 years after surgery | Mortality rates determined both for all-cause mortality and for related deaths only. For the former, the causality status will be determined by the Investigator, and all deaths that are clearly unrelated to the device, the surgery or the underlying medical condition will be excluded from the analysis. |
| Safety: The Occurrence, Frequency and Timing of Treatment-emergent Major Adverse Cardiac Events (MACEs). | From surgery to end of study (2 years) | MACE is defined as stroke and clinically significant myocardial infarction (MI), from surgery to end of study. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Exploratory: Thickness of the Anterior Leaflet Segment A2 and the Posterior Scallop P2 of the Mitral Valve (MV) Leaflets, as Measured With the Dedicated Medtentia Leaflet Measurement Tool. | Day of surgery visit (V01) | — |
| Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | At screening and at each follow-up visit (except for discharge visit, up to 2 years). | — |
| Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | Day of surgery visit (V01) | Duration of the following key stages of the annuloplasty procedure: * MAR implantation time (beginning with the measurement of the annulus size and ending with the completion of the last suture, but not including the time needed to measure leaflet thickness) * MAR rotation time * Suturing time (from start of annulus suturing until last knot) * Aortic clamp time * Cardiac arrest time |
| Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | From screening to end of study (up to 2 years) | Change from screening at each follow-up visit in the following MR parameters, as measured using TTE: * Left ventricular inner dimension systole and diastole assessment by trans-thoracic echocardiography (the dimension of inner edge to inner edge, perpendicular to the long axis of the left ventricle, at the level of the mitral valve leaflet tips, measured at end-systole and end-diastole) * Coaptation height |
Countries
Finland
Participant flow
Recruitment details
All patients were enrolled at Helsinki University Central Hospital from June 2011 to April 2014. During Stage 1 (2011-2012) and Stage 2 (2013-2016) MAR was implanted for 12 patients. 11 of 24 consented patients did not receive MAR due to non-anatomical fit (majority in Stage 1); for 1 patient MAR was replaced before the operation was completed.
Pre-assignment details
Patients qualifying for mitral valve repair surgery according to guidelines from the European Society of Cardiology (ESC) and the American Heart Association (AHA) and meeting pre-operative selection criteria. Successful implantation rate improved significantly during Stage 2 after sizing adjustment of the implant (Regular and Expanded).
Participants by arm
| Arm | Count |
|---|---|
| Medtentia Annuloplasty Ring (MAR) Mitral valve repair using the Medtentia Annuloplasty Ring (MAR)
Mitral valve repair using the Medtentia Annuloplasty Ring (MAR) | 12 |
| Total | 12 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Stage 1: MAR Classic | Adverse Event | 1 |
Baseline characteristics
| Characteristic | Medtentia Annuloplasty Ring (MAR) |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 7 Participants |
| Age, Categorical Between 18 and 65 years | 5 Participants |
| Age, Continuous | 65.5 years STANDARD_DEVIATION 8.3 |
| Left Ventricular Inner Dimension Diastole | 60 millimeters |
| Left Ventricular Inner Dimension Systole | 46 millimeters |
| Mitral valve leaflet coaptation height | 14 millimeters |
| Mitral valve regurgitation Class I | 0 participants |
| Mitral valve regurgitation Class II | 0 participants |
| Mitral valve regurgitation Class III | 0 participants |
| Mitral valve regurgitation Class IV | 11 participants |
| New York Heart Association (NYHA) Functional Capacity Class I | 2 participants |
| New York Heart Association (NYHA) Functional Capacity Class II | 5 participants |
| New York Heart Association (NYHA) Functional Capacity Class III | 4 participants |
| New York Heart Association (NYHA) Functional Capacity Class IV | 1 participants |
| Region of Enrollment Finland | 12 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 9 Participants |
| Smoking status Current smoker | 1 Participants |
| Smoking status Non-smoker/ Former smoker | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 12 |
| other Total, other adverse events | 8 / 12 |
| serious Total, serious adverse events | 7 / 12 |
Outcome results
Primary
Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes From Baseline (SC) to Three Months (V03) as Measured by Trans-thoracic Echocardiography (TTE).
Success will be defined as an improvement in at least 2 degrees in mitral regurgitation (MR) class as described in the ACC/AHA Guidelines for the Management of Patients with Valvular Heart Disease (Bonow, et al., 2008).
Time frame: Time from baseline through V03 (3 months)
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes From Baseline (SC) to Three Months (V03) as Measured by Trans-thoracic Echocardiography (TTE). | 90.91 percentage of participants |
Primary
Safety: All-cause Mortality Occurring in the Time From Surgery Through Hospital Discharge.
Time frame: Time from surgery through hospital discharge, up to 7 days.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Safety: All-cause Mortality Occurring in the Time From Surgery Through Hospital Discharge. | 0 Participants |
Secondary
Performance: Mitral Regurgitation (MR) as Seen in Trans-esophageal Echocardiography (TEE) Performed During Surgery Before and After Annuloplasty.
Success will be defined as no or only residual mitral regurgitation (MR).
Time frame: Day of surgery visit (V01).
Population: The data for this outcome measure was not collected.This was a part of the echocardiography investigation protocol and therefore was not documented on electronic case report form although the surgeon in charge performed the investigation on the operation table.
Secondary
Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes at Each Follow-up Visit (V04-V06) of the Improvement in MR From Screening, as Measured by Trans-thoracic Echocardiography (TTE).
Measurement analysis at 24 months after successful MAR implantation.
Time frame: V06 (24 months)
Population: The study was terminated prematurely. Due to the smaller than planned patient group size no patient data at V04 (6 months) and V05 (12 months) was analyzed for this endpoint. The results provided are only for V06 (24 months).
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Performance: Percentage of Participants With Improvement by at Least 2 Mitral Regurgitation Classes at Each Follow-up Visit (V04-V06) of the Improvement in MR From Screening, as Measured by Trans-thoracic Echocardiography (TTE). | 100 percentage of participants |
Secondary
Safety: 30-day Mortality and Mortality at 3 Months, 6 Months, 1 Year, 1.5 Years and 2 Years.
Mortality rates determined both for all-cause mortality and for related deaths only. For the former, the causality status will be determined by the Investigator, and all deaths that are clearly unrelated to the device, the surgery or the underlying medical condition will be excluded from the analysis.
Time frame: 30 days, 3 months, 6 months, 1 year, 1.5 years and 2 years after surgery
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Safety: 30-day Mortality and Mortality at 3 Months, 6 Months, 1 Year, 1.5 Years and 2 Years. | 0 Participants |
Secondary
Safety: The Occurrence, Frequency and Nature of Abnormalities in the Period From Surgery Through Follow-up (Detailed List in Description Field).
The occurrence, frequency and nature of abnormalities in any of the following: * physical examination * vital signs * electrocardiography (ECG) * echocardiography (ECHO) * Laboratory tests * Chest X-rays (taken only when clinically indicated)
Time frame: From surgery to end of study (2 years).
Population: The study was terminated prematurely. Due to the smaller than planned patient group size no sufficient data was collected for planned analysis of this endpoint.
Secondary
Safety: The Occurrence, Frequency and Timing of Treatment-emergent Major Adverse Cardiac Events (MACEs).
MACE is defined as stroke and clinically significant myocardial infarction (MI), from surgery to end of study.
Time frame: From surgery to end of study (2 years)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Safety: The Occurrence, Frequency and Timing of Treatment-emergent Major Adverse Cardiac Events (MACEs). | 1 Events |
Secondary
Safety: The Occurrence, Nature and Frequency of Device Deficiencies and Adverse Device Effects (ADEs).
Time frame: From surgery to end of study (2 years).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Safety: The Occurrence, Nature and Frequency of Device Deficiencies and Adverse Device Effects (ADEs). | 0 Events |
Secondary
Safety: The Occurrence, Nature and Frequency of Treatment-emergent Adverse Events (AEs), in Particular Severe Serious Adverse Device Effects (SADEs).
All the adverse events reported were non-device related.
Time frame: From surgery to end of study (2 years).
Population: Due to the smaller than planned patient group size the descriptive statistics was used. Adverse events data is presented in Adverse Events section.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Safety: The Occurrence, Nature and Frequency of Treatment-emergent Adverse Events (AEs), in Particular Severe Serious Adverse Device Effects (SADEs). | 30 Events |
Other Pre-specified
Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE.
Change from screening at each follow-up visit in the following MR parameters, as measured using TTE: * Left ventricular inner dimension systole and diastole assessment by trans-thoracic echocardiography (the dimension of inner edge to inner edge, perpendicular to the long axis of the left ventricle, at the level of the mitral valve leaflet tips, measured at end-systole and end-diastole) * Coaptation height
Time frame: From screening to end of study (up to 2 years)
Population: The outcome is reported for subjects and follow up visits where data is available
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Left Ventricular Inner Dimension Systole 3 months | 40 millimeters |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Left Ventricular Inner Dimension Systole 2 years | 38 millimeters |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Left Ventricular Inner Dimension Diastole 3 months | 50 millimeters |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Left Ventricular Inner Dimension Diastole 2 years | 51 millimeters |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Coaptation Height 3 months | 6.2 millimeters |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Change in the Mitral Regurgitation (MR) Parameters, as Measured Using TTE. | Coaptation Height 2 years | 7.3 millimeters |
Other Pre-specified
Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge.
Time frame: At screening and at each follow-up visit (except for discharge visit, up to 2 years).
| Arm | Measure | Group | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 3 monts | Class II | 3 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 3 monts | Class I | 8 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 3 monts | Class III | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 3 monts | Class IV | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 6 months | Class I | 9 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 6 months | Class II | 2 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 6 months | Class III | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 6 months | Class IV | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 1 year | Class I | 10 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 1 year | Class II | 1 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 1 year | Class III | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 1 year | Class IV | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 2 years | Class I | 11 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 2 years | Class II | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 2 years | Class III | 0 Participants |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Changes From Screening in NYHA Classification at All Follow-up Visits Except Discharge. | 2 years | Class IV | 0 Participants |
Other Pre-specified
Exploratory: Duration of the Key Stages of the Annuloplasty Procedure.
Duration of the following key stages of the annuloplasty procedure: * MAR implantation time (beginning with the measurement of the annulus size and ending with the completion of the last suture, but not including the time needed to measure leaflet thickness) * MAR rotation time * Suturing time (from start of annulus suturing until last knot) * Aortic clamp time * Cardiac arrest time
Time frame: Day of surgery visit (V01)
Population: MAR rotation time assessment available for 9 patients only.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | Aortic clamp time | 87.2 minutes | Standard Deviation 24.5 |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | MAR implantation time | 16.9 minutes | Standard Deviation 5 |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | Suturing time | 14.6 minutes | Standard Deviation 4.1 |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | MAR rotation time | 2.5 minutes | Standard Deviation 1.4 |
| Medtentia Annuloplasty Ring (MAR) | Exploratory: Duration of the Key Stages of the Annuloplasty Procedure. | Cardiac arrest time | 116.2 minutes | Standard Deviation 32.8 |
Other Pre-specified
Exploratory: Thickness of the Anterior Leaflet Segment A2 and the Posterior Scallop P2 of the Mitral Valve (MV) Leaflets, as Measured With the Dedicated Medtentia Leaflet Measurement Tool.
Time frame: Day of surgery visit (V01)
Population: The leaflet measuring tool was designed to compress the leaflet between two jaws to measure the thickness. Due to soft tissue getting compressed between these two jaws the measure was not seen accurate, therefore this procedure was omitted in the study.