The objective of this clinical study is to evaluate the safety and performance of the IASD System II in the treatment of heart failure patients with elevated left atrial pressure, who remain symptomatic despite appropriate medical management.
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary safety endpoint is the percent of subjects who experience major
adverse cardiac and cerebrovascular events (MACCE) defined as death, stroke,
MI; or subjects who experience a systemic embolic event (excluding pulmonary
thromboembolism); or subjects who require surgical implant removal within 6
months from day of implant.
The primary device performance endpoints are:
* The percent of subjects who have successful device implantation, defined as
deployment at the intended location during the index procedure
* The percent of subjects with reduction of PCWP, and demonstration of left to
right flow through the device at 6 months
Secondary outcome
1. Incidence of major adverse cardiac events through 6-months post implant
2. Incidence of all serious adverse events (SAEs) through 6-months post implant
3. All-cause, and heart failure related hospitalizations; and number of
hospitalization days, ICU days, through 6 months
4. All-cause mortality, CV mortality and heart failure related mortality
through 6 months
5. Changes in invasive and noninvasive hemodynamic measures (at rest and when
performed at baseline, also during exercise) assessed compared to baseline at 6
months by a core laboratory.
a. The percent of patients with reduction of PCWP below the baseline value at
rest and during exercise;
b. Changes in pulmonary and systemic cardiac output; and in PA pressures
6. Changes in BNP and/or NT-pro-BNP assessed at 6 months compared to baseline
7. Changes in Investigator assessed NYHA classification assessed at 6 months
compared to baseline
8. Changes in RA, LA, LV and RV dimensions, volume, and function as measured by
echocardiography, assessed compared to baseline at 6 months by a core
laboratory
9. Improvement in Quality of Life (QOL) as measure by Minnesota Living with
Heart Failure Questionnaire (MLWHFQ) assessed at 6 months compared to baseline
10. Improvement in QOL as measured by EQ-5D-3L assessed compared to baseline at
6 months
11. Incidence of cerebrovascular events, through 6-months post implant
12. The percent of subjects with an improvement in exercise tolerance as
assessed by 6MWT at 6 months compared to baseline
13. Incidence of newly acquired atrial arrhythmia, through 6-months post
implant
14. Incidence of new onset or worsening of kidney dysfunction (defined as eGFR
decrease of > 20 ml/min) through 6-months post implant
15. Implant embolization and clinically significant device migration, defined
as serious adverse event(s) probably related to device migration
Background summary
Heart failure is defined as a disorder of the heart pump function with
associated symptoms. Symptoms can be very different, but include at least his
fatigue and / or dyspnea.
Mortality is high and depending on the severity of the heart failure. Fifty
percent of patients deceased within five years (with severe heart failure,
within one year) after diagnosis.
The prevalence of heart failure among the population is 2-2.5%. Currently there
are 200,000 patients with heart failure in the Netherlands. The prevalence
increases sharply with increasing age.
With increasing aging population combined with improved medical techniques of
cardiac and non-cardiac diseases, the prevalence of heart failure is increasing.
This study is evaluating a new device (Inter-atriale septum Device (IASD)
System II) that is permanently implanted in the heart and is designed to reduce
the increased pressure due to heart failure, by creating a small permanent
opening between the two upper chambers in the heart. The relief of this
pressure by the study device may reduce some or all of the symptoms a subject
is experiencing.
Study objective
The objective of this clinical study is to evaluate the safety and performance
of the IASD System II in the treatment of heart failure patients with elevated
left atrial pressure, who remain symptomatic despite appropriate medical
management.
Study design
A prospective, Non-randomized; Open label study. Up to 100 subjects at up to 30
investigational Sites will be enrolled in order to obtain 50 subjects with 6
month follow-up.
Intervention
Percutaneous implantation (permanent) of the IAS System II.
Study burden and risks
Heart Catheterization Risks
The main risks of a heart catheterization include but are not limited to:
* pain at the catheter insertion site,
* abnormal heart rate,
* excessive collection of blood at insertion site,
* fever after the procedure,
* significantly increased or decreased blood pressure sometimes requiring
medication,
* blood loss sometimes requiring blood replacement,
* allergic reaction to the dye used to take pictures of the heart,
* temporary stoppage of breathing,
* reaction to the anesthesia medications,
* accidental creation of an abnormal passage between an artery and vein,
* obstruction of a blood vessel by an air bubble,
* blockage of a blood vessel by a blood clot,
* injury to a nerve at the insertion site,
* appearance of a bulge in a blood vessel,
* the tearing or poking of a hole through a blood vessel or heart.
These risks are uncommon. To reduce the likelihood of these risks, the study
sponsor carefully selects and trains, and supports study doctors that have
significant experience with similar types of procedures.
Study Device and Implantation Procedure Risks
The main risks of having the study device implanted are similar to the risks
listed above for heart catheterization.
In addition, the following risks have been identified:
* small clots may form on the implant itself and be released into the blood
circulation.
* stroke,
* heart failure,
* heart attack
* death
* study device embolization: the study device does not stay in place and floats
away into another part of the heart or into a blood vessel..
* One or more of the study device arms rubs or pokes a hole into a blood vessel
or part of the heart. If this happens, urgent surgery may be required to remove
the device and repair the tear or hole.
* Study device fracture : break of one or more of the study device arms once it
is in the heart
* Callous
* Blood clot
* Infection
* Allergic reaction to the study device
* Heart rhythm disturbances (for example, slow rate)
* Perforation of the blood vessel or part of the heart
* Fluid around the heart
* the heart failure does not improve during the study, or worsens.
To minimize those risks, the study doctor has been carefully trained on the
study device placement; in addition:
* the study device is made of materials that were specifically selected because
of their strength and resistance to wear
* the study doctor will give the patient appropriate medications before and
after the procedure, and during the study follow up period to reduce this risk.
* the study doctor uses special imaging equipment during the procedure to see
the study device and make sure it is placed in the correct position in the
heart.
* the study device shape and materials were selected to hold it in place.
* if the device does move out of place during the implant procedure, your study
doctor may use a catheter to retrieve and remove it. If the device moves out
of place after the patient has been discharged from the hospital, the study
device may need to be removed during open heart surgery.
* in the unlikely event that the study device breaks into several pieces, a
piece of it could potentially break off and float away to another place in the
patient's body. Depending on its final location, surgery may be required to
remove the piece and the remaining broken device.
It is not expected that patients enrolled in this study will have these
complications. Side effects are usually temporary and manageable.
If we learn of any new risks while this study is ongoing, the study doctor will
make the patients aware of them as soon as possible.
Exercise Testing Risks
The risks related to the exercise stress test are fatigue, muscle soreness,
irregular heartbeat, chest pain, sudden heart attack, stroke, or death. To
minimize these risks trained medical professionals will be present during this
procedure. In addition, the patient will have his heart rate monitored
continuously throughout the testing. The patient will also have your blood
pressure and your rate of perceived exertion monitored throughout the testing.
Echocardiogram Risks
In addition to the risks listed above, there are possible, although very rare,
risks with echocardiograms. A potential risk of the echocardiogram when the
tube is placed into the patient's esophagus is a tear or poking of your
esophagus, the tube connecting the mouth to the stomach. This tear could cause
bleeding or infection that is potentially life threatening, and in some cases
may require surgery for repair. If the study doctor uses intra-cardiac
echocardiogram during the implant procedure, potential risks are puncture of a
blood vessel as it travels to the heart or puncture of the heart, both of which
may be life threatening and may require urgent surgery to correct. To reduce
the likelihood of these unlikely risks, specially trained doctors perform these
procedures.
Blood Test Risks
There are some side effects that can happen when the patient has blood drawn.
This includes excessive bleeding, fainting or feeling light-headed, hematoma
(blood pooling under the skin), infection (a slight risk any time the skin is
broken).
Pregnant women
This treatment may have unforeseeable risks the embryo or foetus if the subject
ispregnant at the moment of the procedure. Woman of childbearing age and
fertile are not authorized to take part of this clinical trial.
Benefits
There is no guarantee that the subject will benefit from participation in this
study.
Potential benefits to patients implanted with the study device include the
following:
* Reduction in shortness of breath
* Reduction in the number of hospitalizations and/or hospital days
* Reduction in the number of emergency room visits
* Reduction in medications
* Improved exercise tolerance
* Improved quality of life
* Improved life expectancy
By participating in this study, the patient will help others by providing
information that may be used to develop new treatments for patients with
similar conditions.
One Highwood Drive, Suite 300, Tewksbury 300
Tewksbury MA 01876
US
One Highwood Drive, Suite 300, Tewksbury 300
Tewksbury MA 01876
US
Listed location countries
Age
Inclusion criteria
Candidates for the study must meet ALL of the following inclusion criteria:
1. Chronic symptomatic Heart Failure (HF) documented by one or more of the following:
a. New York Heart Association (NYHA) Class II/III/ambulatory class IV symptoms (Paroxysmal nocturnal dyspnea, Orthopnea, Dyspnea on mild or moderate exertion) at screening visit; or signs (Any rales post cough, Chest x-ray demonstrating pulmonary congestion,) within past 12 months;
b. One hospital admission for which HF was a major component of the hospitalization within the 12 months prior to study entry (transient heart failure in the context of myocardial infarction does not qualify);
c. On-going management with recommended heart failure medications and comorbidities for several months according to the guidelines (2012 ESC Guidelines for diagnosis and Treatment of Acute and Chronic Heart Failure).
2. Age * 40 years old
3. Left ventricular ejection fraction (obtained by echocardiography) * 40%
4. Elevated left ventricular filling pressures with a gradient compared to CVP documented by :
a. PCWP (end expiratory) or LVEDP (end expiratory) at rest * 15 mmHg, and greater than CVP, OR
b. PCWP (end expiratory) during supine bike exercise * 25mm Hg, and CVP < 20 mm Hg
5. Subject has been informed of the nature of the study, agrees to its provisions and has provided written informed consent, approved by the EC
6. Subject is willing to comply with clinical investigation procedures and agrees to return for all required follow-up visits, tests, and exams
7. Trans-septal catheterization and femoral vein access is determined to be feasible
Exclusion criteria
Candidates for this study will be excluded if ANY of the following conditions are present:
1. MI and/or percutaneous cardiac intervention within past 3 months; CABG in past 3 months, or current indication for coronary revascularization
2. Cardiac Resynchronization Therapy initiated within the past 6 months
3. Severe heart failure defined as:
a. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF;
b. Cardiac Index < 2.0 L/min/m2
c. Requiring inotropic infusion (continuous or intermittent) within the past 6 months
d. Patient is on the cardiac transplant waiting list
4. Inability to perform 6 Minute Walk Test
5. Known significant coronary artery disease (stenosis >70%)
6. History of stroke, transient ischemic attack (TIA), deep vein thrombosis (DVT), or pulmonary emboli within the past 6 months
7. Known severe carotid artery stenosis (> 70%)
8. Presence of significant valve disease defined by echocardiography as:
a) Mitral valve regurgitation defined as grade >2+ MR
b) Tricuspid valve regurgitation defined as grade * 2+ TR;
c) Aortic valve disease defined as * 2+ AR or moderate AS
9. Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac Amyloidosis or other infiltrative cardiomyopathy (e.g. hemochromatosis, Sarcoidosis)
10. Subject is contraindicated to receive either dual antiplatelet therapy or warfarin analogue; or has a documented coagulopathy
11. Atrial fibrillation with resting HR > 100 BPM
12. Arterial Oxygen saturation < 95% on room air
13. Significant hepatic impairment defined as 3X upper limit of normal of transaminases, total bilirubin, or alkaline phosphatase
14. Right ventricular dysfunction, defined as
a. More than mild RV dysfunction as determined by TTE: OR
b. TAPSE < 1.4 cm: OR
c. RV volume * LV volume on echo estimate; OR
d. Echocardiographic or clinical evidence of congestive hepatopathy
15. Resting CVP > 14 mmHg
16. Evidence of pulmonary hypertension with PVR > 4 Woods Units (mm Hg/L/min)
17. Chronic pulmonary disease requiring home oxygen, OR hospitalization for exacerbation in the 6 months prior to study entry, OR significant chronic pulmonary disease defined either as FEV1 <1, or in the opinion of the investigator
18. Currently participating in an investigational drug or device study. Note: Trials requiring extended follow-up for products that were investigational but have since become commercially available are not considered investigational trials
19. Life expectancy less than 12 months for non-cardiovascular reasons
20. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation.
21. Known or suspected allergy to nickel
22. Fertile women
23. Currently requiring dialysis; or e-GFR <25ml/min
24. SABP >170 despite appropriate medical management
25. Subjects in whom trans-esophageal echocardiography (TEE) is contraindicated
26. Subjects with existing Atrial Septal Defects. Subjects with a Patent Foramen Ovale (PFO), who have elevated filling pressure despite the PFO are allowed.
27. Subjects on immunosuppression or systemic steroid treatment (>10 mg prednisone/day)
28. Subjects who have diagnosed scleroderma
29. In the opinion of the investigator, the subject is not an appropriate candidate for the study
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 | NCT01913613 |
| CCMO | NL46012.100.13 |