The objective of this study is to evaluate the safety and efficacy of the AccuCinch Ventricular Restoration System in patients with symptomaticheart failure with reduced ejection fraction (HFrEF).
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
6-Month Primary Safety & Efficacy Endpoints (~250 subjects randomized 1:1):
• Safety Endpoint: (~125 Treatment group subjects)
Freedom from device- or femoral artery access-related major adverse events
(MAEs) through 6 months where MAEs are defined as the composite of:
a. All-cause death;
b. Stroke;
c. Myocardial infarction;
d. Need for non-elective cardiovascular surgical procedures to treat:
i. Femoral artery access events,
ii. Pericardial effusions or tamponade,
iii. Aortic valve damage,
e. Need for mechanical circulatory support for more than 24 hours due to
worsening heart failure or hemodynamic instability;
f. Acute kidney injury requiring renal replacement therapy
• Efficacy Endpoints
Change from baseline at 6 months:
a. Kansas City Cardiomyopathy Questionnaire Quality of Life Questionnaire
Overall Score (KCCQ-OS)
b. 6-Minute Walk Test (6MWT)
12-Month Safety & Efficacy Endpoints (~400 subjects randomized 1:1):
• Safety Endpoint: (~200 Treatment group subjects)
Freedom from device- or femoral artery access-related major adverse events
(MAEs) through 12 months where MAEs are defined as the composite of:
a. All-cause death;
b. Stroke;
c. Myocardial infarction;
d. Need for non-elective cardiovascular surgical procedures to treat:
i. Femoral artery access events,
ii. Pericardial effusions or tamponade,
iii. Aortic valve damage;
e. Need for mechanical circulatory support for more than 24 hours due to
worsening heart failure or hemodynamic instability;
f. Acute kidney injury requiring renal replacement therapy
• Efficacy Endpoint
A hierarchical composite endpoint at 12 months, evaluated using the Win Ratio
method:
a. All-cause death,
b. LVAD implant or heart transplant,
c. Number of heart failure hospitalizations,and
d. Change from baseline KCCQ-OS score
Secondary outcome
Secondary Safety & Efficacy Endpoints (~400 subjects randomized 1:1):
• Secondary Safety Endpoints
To be evaluated at 1-month, 3-month, 6-month, 12-month, 18-month and 2-year
follow-up visits:
a. All-cause death or all-cause hospitalizations
b. All-cause death
c. All-cause hospitalizations
d. Incidence of all serious adverse events, including device and procedure-
related complications
• Secondary Efficacy Endpoints
Changes from baseline to 1-month, 3-month, 6-month, 12-month,18-month and
2-year follow-up visits:
a. NYHA Functional Class
Changes from baseline to 1-month, 3-month, 12-month, 18-month and 2-year
follow-up visits
a. KCCQ-OS
b. 6-Minute Walk Test
Changes from baseline and from post-procedure/pre-hospital discharge to
1-month, 3-month, 6-month, 12-month and 2-year follow-up visits as assessed by
echo:
a. Left ventricular ejection fraction (LVEF)
b. Left ventricular end-diastolic volume (LVEDV)
c. Left ventricular end-systolic volume (LVESV)
To be evaluated at 1-month, 3-month, 6-month, 12-month, 18-month and 2-year
follow-up visits:
a. CV death
b. HF death
c. HF-related hospitalizations
Background summary
Reduced Ejection Fraction Heart Failure (HFrEF) has been singled out as an
epidemic and is a staggering clinical and public health problem
associated with significant mortality, morbidity, and healthcare expenditures,
particularly among those aged >=65 years. After the diagnosis of HF, survival
estimate is 50% at 5 years, and left ventricular dysfunction is associated with
an increase in the risk of sudden death.
Study objective
The objective of this study is to evaluate the safety and efficacy of the
AccuCinch Ventricular Restoration System in patients with symptomatic
heart failure with reduced ejection fraction (HFrEF).
Study design
The CORCINCH-HF Study is a prospective, randomized, open-label, multicenter,
international, clinical safety and efficacy investigation of the AccuCinch
Ventricular Restoration System. The study will be conducted in two phases.
Phase 1 will evaluate the safety of the AccuCinch treatment with respect to
pre-defined MAEs compared to a pre-specified
performance goal and the efficacy of the AccuCinch treatment as compared to the
Control group with respect to quality of life (via Kansas City Cardiomyopathy
Questionnaire overall score, KCCQ-Overall Score) and exercise tolerance (via
6-minute walk test distance, 6MWT), evaluated at 6 months of follow-up. Phase 2
will evaluate the safety of the AccuCinch treatment with respect to pre-defined
MAEs compared to a pre-specified performance goal and the efficacy of the
AccuCinch treatment using a hierarchical composite of death, left ventricular
assist device use, the need for heart transplant, the total number of heart
failure hospitalizations and quality of life (by KCCQ-OS) compared to the
Control group, evaluated at 12 months of follow-up.
Subjects will be randomized in a 1:1 ratio:
a) Treatment group: AccuCinch Ventricular Restoration System plus
guideline-directed medical therapy (GDMT) (n~200)
b) Control group: Guideline-directed medical therapy (GDMT) (n~200)
Randomization will be stratified by study site and by ischemic versus
nonischemic dilated cardiomyopathies.
The final primary endpoints of the study will be evaluated at 12 months.
Subjects will be followed through 5 years. Control subjects will be given an
opportunity to cross-over to device treatment after the 24-month visit if they
still meet study entry criteria. Such subjects will be followed according to
the same schedule of events as subjects initially randomized to the Treatment
group for a total of 7 years of study participation.
Intervention
During the procedure you will be put to sleep under general anesthesia. Your
study doctor will do a right heart catheterization to see how well or poorly
your heart is pumping. In a right-heart catheterization, your study doctor
guides a special catheter (a small, hollow tube), called a pulmonary artery
(PA) catheter, into the right side of your heart. He or she then passes the
tube into your pulmonary artery, this is the main artery that carries blood to
your lungs. Your study doctor observes blood flow through your heart and
measures the pressures inside your heart and lungs during the procedure.
Your study doctor will then make the final determination to proceed with the
AccuCinch device implantation.
You will have a Transesophageal Echocardiogram (TEE), which is a type of
imaging where a long, thin tube is placed through your mouth and into your
esophagus (*food tube*) to guide an ultrasound probe to see pictures of your
heart. This is to help your study doctor see your heart, study catheters and
the AccuCinch device during the implant procedure.
During the procedure, you will receive injections of dye and x-ray radiation so
that the physician can determine the correct placement of the device. Your
blood pressure will be monitored throughout the entire procedure through a tube
in your blood vessel. Your study doctor may also give you antibiotics to reduce
the chance of infection.
Your study doctor will insert the AccuCinch device through the main blood
vessel in your groin and implant the device in your heart through a special
catheter (a small hollow tube that is slightly smaller in diameter than a
pencil). Your study doctor will place 10-16 small anchors underneath your
mitral valve. A strong, thread-like cord will be threaded through these anchors
and will be tightened to reduce the size of the pumping chamber of your heart.
Study burden and risks
POTENTIAL RISKS OF ROUTINE TESTS AND PROCEDURES
The potential risks associated with the screening and implant procedure may
include, but are not limited to, the following:
• Allergic reaction to antithrombotic therapy (blood thinners), contrast medium
(dye used for some x-ray procedures to allow visibility of structures inside
your body), medication, or anesthesia
• Anemia (reduced number of red blood cells)
• Angina (chest pain)
• Aortic dissection (tearing of your primary blood vessel)
• Aortic valve thrombosis/occlusion (aortic valve becoming obstructed or
blocked with a blood clot)
• Arrhythmias (irregular heartbeat) that may require you to undergo external
electrical shocks
• Arteriovenous fistula (cross-mingling of blood between an artery and vein due
to vessel damage)
• Bleeding or bruising
• Blood loss requiring blood transfusion
• Cardiac arrest (your heart stops beating, requiring chest compressions and/or
shocks to re-start it)
• Cerebrovascular accident (including stroke or transient ischemic attack (TIA)
in which there is sudden death of brain cells due to lack of blood flow to them
with may cause symptoms of brain damage)
• Conduction disturbances (problem with the electrical system of your heart
that makes your heartbeat and controls its rate and rhythm)
• Death
• Emboli (air, tissue, thrombotic) (air bubbles, small particles of tissue, or
small blood clots released into the blood stream)
• Endocarditis (infection in your heart)
• Esophageal (food tube) irritation/pain, damage or rupture
• Gastrointestinal symptoms (having a stomachache or poor bowel function)
• Headache
• Heart failure
• Hematologic dyscrasia (a disorder of the blood cells)
• Hematoma (blood accumulation under the skin where it was cut or punctured)
• Hemolysis (damage to the red blood cells causing weakness, or tiredness and
possibly requiring transfusion)
• Hemorrhage (a rapid loss of blood)
• Hypertension/Hypotension (high blood pressure/low blood pressure) requiring
medication or device support
• Infection and/or pain at access site (where your skin was cut or punctured)
• Infection, fever
• Infection, systemic sepsis (infection of your whole body (sepsis)
• Intervention/conversion to open heart surgery
• Ionizing radiation risks
• Myocardial ischemia (blood flow to the heart is reduced, preventing the heart
muscle from receiving enough oxygen) or Heart Attack
• Perforation (a hole) or rupture of the heart structure
• Pericardial effusion/cardiac tamponade (fluid collection between the heart
and the sac surrounding the heart)
• Pericarditis (an inflammation of the sac-like tissue that surrounds the heart)
• Peripheral ischemia (not enough blood supply to the arm or leg caused by
narrowing or obstruction in the blood vessels).
• Peripheral (leg or arm) nerve injury/paralysis
• Pleural effusion (fluid collection in or around your lung or heart causing
shortness of breath)
• Pneumonia (infection that inflames air sacs in one or both lungs)
• Pneumothorax (air enters the space between the lung and the chest wall)
• Postoperative encephalopathy (brain disease, damage or malfunction)
• Pseudoaneurysm (leakage of blood out of a blood vessel that is contained by
surrounding tissue)
• Pulmonary edema (fluid build-up in your lungs)
• Renal insufficiency/failure (poor kidney function or worsening of kidney
function)
• Respiratory insufficiency/failure (poor lung function or worsening of lung
function)
• Shock, anaphylactic (life-threatening allergic reaction) or cardiogenic (poor
pumping function of your heart)
• Thrombocytopenia (blood disorder)
• Vessel spasm
• Vessel thrombosis (blood clot formation)/occlusion (blockage)
• Vessel trauma requiring surgical repair or intervention
POTENTIAL RISKS OF ACCUCINCH SYSTEM
In addition to the potential risks listed above, the following risks associated
with AccuCinch device include, but are not limited to:
• Allergic/immunologic reaction to the implant
• Aortic valve insufficiency (leaking of the valve between the main blood
vessel that carries blood away from your heart to the rest of your body and the
lower chamber of the left side of your heart)
• Aortic valve trauma
• Component embolization (any part of the device that that is released in the
bloodstream and causes a sudden block in the blood vessel)
• Left ventricular outflow tract (LVOT) obstruction (a blockage of blood flow
as blood is pumped from the main pumping chamber of the heart)
• Loss of therapy or benefit if the Cable breaks as the AccuCinch device
becomes part of the wall of your heart
• Mitral valve apparatus damage (damage to the heart valve the separates the
upper and lower chamber of the left side of your heart)
• Mitral valve stenosis (narrowing of the heart valve opening between the upper
chamber to lower chamber of the left side of your heart)
• Worsening mitral regurgitation (leakage of blood from the lower chamber of
your heart to the upper chamber)
As with any research study, there is also the possibility of side effects not
presently known. The study doctor and research staff will make every effort to
minimize additional risks. As the research study progresses, you will be
informed of any new study results that may affect your willingness to remain in
the research study.
If you are female, you should not become pregnant or breastfeed a child while
in this study. If you are sexually active and are able to become pregnant, you
must use an acceptable form of birth control while you are in this study. Your
study doctor will talk with you about the types of birth control that are
acceptable to use while being in this study. Tell the study doctor right away
if you become pregnant or think you are pregnant.
BENEFITS OF SCREENING TESTS AND/OR PROCEDURE
You may or may not receive any direct benefit from this research study.
SCREENING TESTS: The potential benefit from undergoing these screening
assessments is that you will have undergone a thorough examination of your
medical condition and you may have a better understanding of the available
therapies for your condition.
PROCEDURE: If you are in the Device Group and the AccuCinch device has been
implanted, you may experience an improvement in the symptoms related to your
dilated heart. The study procedure techniques include a less invasive
procedure than open-heart surgery, and it is anticipated that the study
procedure will take less time and less anesthesia than an open-heart surgery.
Treatment with the study device may provide both short and long-term relief of
your symptoms, and an improvement of your cardiac function that could
potentially increase both your life expectancy and improve your quality of life.
It is possible that you will receive no direct benefit from this research
study, but others may benefit in the future from the results of your
participation.
Burton Dr. 4001
Santa Clara CA 95054
US
Burton Dr. 4001
Santa Clara CA 95054
US
Listed location countries
Age
Inclusion criteria
1. Age 18-years or older
2. Ejection Fraction: >=20 and <=40% measured by transthoracic echocardiography
(TTE) and assessed by an echocardiography (echo) core lab
3. LV end-diastolic diameter >=55 mm measured by TTE and assessed by an echo
core lab
4. Symptom Status:
a. NYHA III,
b. NYHA ambulatory IV, or
c. NYHA II with a heart failure hospitalizationa within the prior 12 months (of
signing the consent)
5. Able to complete six-minute walk test with distance between 100 m and 450 m
6. Diagnosis and treatment for heart failure should be established at least 90
days before the date of consent
7. Prior to randomization, subjects should be on stable, optimally titrated
medical therapy for at least 30 days, as recommended according to current
guidelines as standard-of-care for Heart Failure therapy, with any intolerance
documented
8. Able and willing to complete all qualifying diagnostic and functional tests,
willing to accept blood product transfusion if required and agrees to comply
with study follow-up schedule
Exclusion criteria
Cardiovascular
1. Myocardial infarction or any percutaneous cardiovascular intervention,
cardiovascular surgery, or carotid surgery within 90 days prior to consent
2. Untreated clinically significant coronary artery disease (CAD) requiring
revascularization
3. Computed tomographic (CT), fluoroscopic or echocardiographic evidence of
severe aortic arch calcification, mobile aortic atheroma, intracardiac mass,
thrombus or vegetation
4. Suboptimal ventricular anatomy or wall thickness as determined from
screening echocardiography and/or CT scan
5. Heart failure on the basis other than ischemic or non-ischemic dilated
cardiomyopathy (e.g., hypertrophic cardiomyopathy, amyloid cardiomyopathy,
restrictive cardiomyopathy, uncorrected congenital heart disease, constrictive
pericarditis)
6. Hemodynamic instability within 30 days prior to the implant defined as
subject requiring inotropic support or mechanical hemodynamic support (e.g.,
left ventricular assist device (LVAD))
7. Any planned cardiac surgery or interventions within the next 180 days
post-randomization (including therapeutic right heart procedures)
8. Active bacterial endocarditis
9. Severe RV dysfunction assessed by right heart catheterization (RHC) and/or
TTE
10. Fixed pulmonary hypertension with PA systolic pressure >70 mmHg not
responsive to vasodilator therapy
11. History of any stroke within the prior 90 days of consent or documented
Modified Rankin Scale >= 2 disability from any prior stroke
Valvular
12. Mitral regurgitation grade 3+ (moderate-severe) or 4+ (severe)
13. Untreated degenerative (primary) mitral valve disease (mild prolapse with
no need for intervention is allowable)
14. Prior mitral or aortic valve replacement
15. Tricuspid regurgitation grade 4+ (severe)
16. Moderate or severe aortic valve stenosis (AVA less than 1.5 cm2 or peak
velocity AV Vmax >300 cm/sec)
17. Aortic regurgitation grade 2+ (moderate), 3+ (moderate-severe), or 4+
(severe)
Procedural
18. Anatomical pathology or constraints preventing appropriate access/implant
of the AccuCinch Ventricular Restoration System (e.g., femoral arteries will
not support a 20F Introducer sheath)
19. Renal insufficiency (i.e., eGFR of <25 ml/min/1.73 m2)
20. Subjects in whom anticoagulation during the procedure is contraindicated
21. Subjects in whom 90 days of antiplatelet therapy is contraindicated
22. Known allergy to nitinol, polyester, or polyethylene
23. Any prior true anaphylactic reaction to contrast agents; defined as known
anaphylactoid or other non-anaphylactic allergic reactions to contrast agents
that cannot be adequately pre-medicated prior to the index procedure
General
24. Life expectancy <1 year due to non-cardiac conditions
25. Currently participating in another interventional investigational study
26. Subjects on high dose steroids or high dose immunosuppressant therapy
27. Female subjects who are pregnant, of child-bearing potential without a
documented birth control method, or who are 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 | NCT04331769 |
| CCMO | NL83077.000.23 |