To evaluate the long-term safety and performance of the HARPOON* MVRS for use in patients presenting with severe degenerative mitral regurgitation due to posterior leaflet prolapse in the post-market phase.
ID
Source
Brief title
Condition
- Cardiac valve disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary Safety Endpoint:
Freedom from all-cause mortality, disabling stroke and life- threatening
bleeding at 30 days post-implant.
Primary Performance Endpoint:
Procedure success at 30 days post-treatment, as measured by: Technical success
with reduction of MR to less than or equal to mild and the absence of major
device or procedure-related SAEs.
Secondary outcome
- Technical success defined as survival and exit from the operating room (OR)
with successful implantation of 3 or more expanded polytetrafluoroethylene
(ePTFE) chords.
- Freedom from major device or procedure-related serious adverse event (SAE) at
30 days, 1 year and 2 years post-implant
- Quality of Life (change from baseline to 1 and 6 months)
- 6-minute walk test (change from baseline to 1 and 6 months)
- Freedom from ePTFE chord rupture as reported by echo core lab at 1 year and 2
years post-implant
- Freedom from reoperation or re-intervention due to ePTFE chord rupture at 1
year and 2 years post-implant
- Functional improvement from baseline NYHA Functional Classification at 1 year
and 2 years post-implant
- Freedom from reoperation or reintervention on the mitral valve annually
through 5 years post-implant
- Freedom from >= moderate MR annually through 5 years post-implant
Background summary
Mitral valve disease is the second most common valvular heart disorder
requiring surgery in Europe, with nearly 8 million Europeans estimated to have
severe mitral valve regurgitation (MR) (AGENAS, 2015). MR results in a volume
overload on the left ventricle which in turn leads to ventricular dilation,
decreased ejection performance, pulmonary hypertension, symptomatic congestive
heart failure, atrial fibrillation, right ventricular dysfunction and death.
Successful surgical mitral valve repair restores mitral valve function,
eliminates volume overload on the left ventricle, improves symptom status and
prevents adverse left ventricular remodelling.
The large majority of MR results from either degenerative disease (caused by
elongated or ruptured native chords that fail to support the mitral valve
leaflets) or functional ischemic or idiopathic MR (the motion of the normal
mitral valve leaflets is restricted by the enlarged ventricle) both of which
lead to ineffective valve closure and regurgitation. Other less common causes
of chronic primary MR include infective endocarditis, connective tissue
disorders, rheumatic heart disease, cleft mitral valve, and radiation heart
disease. If the subsequent volume overload of chronic primary MR is prolonged
and severe, it causes myocardial damage, heart failure (HF), and eventual
death. Correction of the MR is curative (Nishimura et al., 2014).
There is no effective medical treatment for degenerative MR (DMR). Medical
treatment, e.g. diuretics, vasodilators, might relieve HF symptoms but does not
alter the course of DMR and ultimately surgery will be required (Nishimura et
al., 2016). Two-thirds of all mitral valve surgical procedures in North
America are performed on patients with degenerative MR and that percentage is
estimated to be similar in Europe. Open cardiac surgery is a common method of
treating DMR which involves replacing and/or supplementing elongated or
ruptured chords with artificial chords made of ePTFE, a commercially available
material which has a 20+ year history of safety in conventional mitral valve
repair procedures.
Current ESC/EACTS Guidelines state that surgery is indicated in:
• asymptomatic patients with LVEF <=60% or LVESD >=45mm, new onset AF or SPAP
>50mmHg and who are at low surgical risk;
• symptomatic MR patients with LVEF >30% or those who are refractory to medical
treatment and in whom a durable valve repair is likely with low comorbidity.
In all patients, valve repair rather than valve replacement is advocated
whenever possible and is now the standard of care (Vahanian et al. 2012). A
systematic review found that mortality is particularly high in patients >80
years old: 10% for MV replacement (N=3,105) compared with 7% for MV repair
(N=2,642), with 5-year survival rates of 23% for MV replacement (N=335) and 29%
for MV repair (N=250). It was concluded that many patients are unfit for major
heart surgery (Andalib et al. 2014).
Although open-heart surgery is the gold-standard approach for the treatment of
severe MR, it is not performed in up to 50% of patients due to the increased
risk associated with co-morbidities. Excellent outcomes can be achieved in most
patients with minimally invasive approaches and transcatheter mitral
interventions might be an alternative therapeutic option (Maisano et al. 2015;
Lam et al. 2011).
Mitral valve repair technologies, including the HARPOON* Beating Heart MVRS
(Chordal repair), can be used in cases of DMR. The other available treatments
to replace ruptured or elongated chordae tendinae can reduce MR. However,
other than the HARPOON* Beating Heart Mitral Valve Repair System, there is no
currently effective medical therapy that treats or cures MR.
Study objective
To evaluate the long-term safety and performance of the HARPOON* MVRS for use
in patients presenting with severe degenerative mitral regurgitation due to
posterior leaflet prolapse in the post-market phase.
Study design
A single arm, prospective, multicentre, non-randomised and open-label
post-market study.
Study burden and risks
The following is not Standard of Care:
- Study Consent form to be signed.
- STS-risk score prior to the surgery.
- 2 Quality of life questionnaires (SF-36 & KCCQ) to be filled in at 30 days
and 6 month follow-up visits.
- 6 minute walk test at 6 month follow-up visits.
- Follow-up visits at 6, 12, 18, 36, 48 and 60 month including all per protocol
required assessments.
Risks associated; Participation in the ASCEND study carries additional
assessments and imaging above the standard-ofcare. Specifically, study subjects
will be assessed via transthoracic echocardiogram (TTE) more often than they
would outside of a clinical study. The risk of TTE, however, as it is based on
ultrasound technology, is minimal.
Other than the TTE, all other study-specific assessments are simply clinic and
physical assessments that would be within the range of standard follow-up of
patients with a MR history.
An additional risk of participating in a clinical study is the risk of a lapse
of confidentiality or exposure of personal identifying information.
Risk-benefit analysis; The risk involved in the clinical study is minimised due
to the fact the device being used is CE-marked and the study design falls
within the intended use population. The risk of participating in the study is
only minimally increased as compared to receiving the device outside the study,
as there is a higher degree of imaging (TTE) and clinical assessment than would
be present otherwise. Additionally, there are the risks involved in data
collection. These risks, though, have been mitigated by the benefit of
additional clinical follow-up and closer care, as well as procedures which have
been put in place to protect subjects* personal information.
One Edwards Way 1
Irvine CA92614
US
One Edwards Way 1
Irvine CA92614
US
Listed location countries
Age
Inclusion criteria
Each subject is required to meet all of the following inclusion criteria:
1. Subject is > 18 years old
2. Presence of severe MR as read on a transthoracic echocardiographic study
3. Mitral leaflet coaptation surface is sufficient to reduce mitral
regurgitation without undue leaflet tension (approximate leaflet to gap ratio
of 2:1) based on the judgment of the patient eligibility committee and the
operating surgeon
4. Degenerative mitral valve disease with mid-segment P2 prolapse
5. Patient is able to sign informed consent and able to return for follow-up
and is capable of participating in all testing associated with this clinical
investigation
Exclusion criteria
A subject meeting any of the following criteria shall be excluded:
1. Patient is of the age where further growth is expected
2. Active endocarditis
3. Left ventricular or left atrial appendage thrombus
4. Severe mitral annular and/or leaflet calcification
5. Cannot tolerate procedural anticoagulation or post-procedure antiplatelet
regimen
6. Mitral stenosis
7. Functional Mitral Valve disease
8. Previous mitral valve replacement surgery
9. Fragile or thinning apex
10. Contraindications to transoesophageal echocardiography (atlantoaxial
disease, severe generalized cervical arthritis, upper gastrointestinal
bleeding, significant dysphagia and odynophagia, has received extensive
radiation to the mediastinum)
11. Patient is pregnant or lactating
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| ClinicalTrials.gov | NCT04382612 |
| CCMO | NL75980.100.20 |