The primary objective of this randomized controlled clinical trial is to evaluate the clinical efficacy and safety of the IASD System II in symptomatic heart failure patients with an LV ejection fraction >=40%, and elevated left sided filling…
ID
Source
Brief title
Condition
- Heart failures
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is the composite of (a) incidence of and
time-to-cardiovascular mortality or first non-fatal, ischemic stroke through 12
months; (b) total rate (first plus recurrent) per patient year of heart failure
(HF) events, defined as hospital admissions, acute healthcare facility
visits, or urgent unscheduled outpatient visits for IV diuresis or
intensification of oral diuretics for HF up to 24 months, analyzed when the
last randomized subject completes 12 months follow-up, and time-to-first HF
event; and (c) change in baseline KCCQ total summary score at 12 months.
Secondary outcome
Major Secondary endpoints:
1. Composite safety endpoint defined as follows:
a. Cardiovascular mortality through 12 months;
b. Non-fatal, ischemic stroke through 12 months
c. New onset or worsening of kidney dysfunction (defined as eGFR decrease of >
20 ml/min) through 12 months
d. Major adverse cardiac events through 12-months defined as
i. Cardiac death;
ii. Myocardial infarction
iii. Cardiac tamponade
iv. Emergency cardiac surgery
e. Thrombo-embolic complications (TIA, systemic embolization) through 12 months
f. Newly acquired persistent or permanent AF or atrial flutter through
12-months
g. >=30% increase in RV size/decrease in TAPSE through 12-months
Secondary Outcome Measures
Safety related outcome measures:
1. All serious adverse events (SAEs) through 12-months
2. All-cause mortality through 12-months
3. Heart failure related mortality through 12-months
4. Implant embolization and clinically significant device migration through
12-months
5. The need for implant removal or occlusion of the implant through 12-months.
Efficacy related outcome measures:
6. Total rate (first plus recurrent) per patient year of heart failure (HF)
events, defined as hospital admissions, acute healthcare facility visits, or
urgent unscheduled outpatient visits for IV diuresis or intensification of
oral diuretics for HF up to 24 months through last follow-up, analyzed when
the last randomized patient completes 12 months follow-up
7. Number of heart failure related hospitalization days and number of all ICU
days through last follow-up, analyzed when the last randomized patient
completes 12 months follow-up
8. Treatment for outpatient worsening of heart failure through 12 months
9. Days alive, and days not-hospitalized through last follow-up, analyzed when
the last randomized patient completes 12-months follow-up
10. Change in diuretic medications (number of medications and dosages) between
baseline and 6 & 12 months.
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 CE marked 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 primary objective of this randomized controlled clinical trial is to
evaluate the clinical efficacy and safety of the IASD System II in symptomatic
heart failure patients with an LV ejection fraction >=40%, and elevated left
sided filling pressures despite standard Guideline Directed Medical Therapy
(GDMT).
Study design
Multicenter, Prospective, Randomized Controlled, Blinded Trial, with a
Non-implant Control group; 1:1 randomization. Patients will be followed for 1
year, and annually every 12 months for a total of 5 years after index procedure
and implant.
Intervention
Percutaneous implantation (permanent) of the IAS System II.
Study burden and risks
To reduce the likelihood of the risks described below, the study sponsor
carefully selects and supports study doctors that have significant experience
with similar types of invasive heart procedures. If you would like more
information about how these risks are managed by your doctors, do not hesitate
to ask.
*
Heart Catheterization Risks
The invasive hemodynamic study and the implantation of the IASD are heart
catheterization procedures. The possible risks and side effects of a heart
catheterization include but are not limited to:
Occasional - with approximately a 10% chance of occurring:
• pain at the catheter insertion site,
• temporary abnormal heart rate,
• excessive collection of blood at the catheter insertion site.
Less common - with 1% - 9% chance of occurring:
• fever after the procedure,
• significantly increased or decreased blood pressure sometimes requiring
medication,
• blood loss sometimes requiring blood replacement,
• allergic reaction to the contrast liquid used with the fluoroscopy,
• temporary renal impairment from the procedure medicines or contrast liquid.
• temporary stoppage of breathing,
• reaction to the sedation 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,
• or the tearing or poking of a hole through a blood vessel or heart.
Uncommon - with less than 1% chance of occurring:
• Infection at the catheter insertion site
• Irregular heart beat or rhythm
• Kidney Injury
Rare - with less than 0.1 % chance of occurring:
• Heart attack (infarction)
• Stroke
• Death
IASD System and Implantation Procedure Risks
Complications associated with implantation of the IASD and similar procedures
in which implants are placed on the atrial septum include the following:
• Adverse dye reaction
• Allergic reaction to implant
• Apnea
• Arrhythmia
• Bleeding, with possible need for blood transfusion
• Blood clot
• Cardiac arrest
• Cardiac perforation from trans-septal puncture
• Chest pain
• Death
• Decreased cardiac output
• Device embolization, whole or partial
• Device Fracture
• Device Mal-deployment
• Endocarditis
• Fever
• Gastro-esophageal perforation associated with trans-esophageal
echocardiography
• Headache, migraine
• Hematoma at access site
• Hemolysis
• Hypotension/Hypertension
• Infection, including sepsis
• Intervention or surgery to remove a mal-deployed or embolized device
• Intracardiac lead entrapment causing device malfunction, valve dysfunction,
or difficulty to exchange a lead
• Pain or nerve damage at access site
• Paradoxical embolus
• Pericardial tamponade
• Perforation or erosion of vessel or myocardium
• Pleural or pericardial effusion
• Pseudo aneurysm at access site
• Reduced L*R shunt/Occlusion of IASD
• Renal failure
• Stroke
• Systemic embolization (air, tissue or thrombus)
• Thrombosis
• Unfavorable response to anesthesia
• Worsening heart failure
Intra-cardiac Echocardiography Risks
The main risks of an intra-cardiac echo include but are not limited to:
• irregular heart rhythms, which may need treatment,
• bleeding where the catheter was put into your blood vessel,
• a blood clot could form, and
• the catheter may damage a blood vessel, for example, where the catheter was
inserted.
Other possible risks of intra-cardiac echo 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 need urgent surgery to
correct.
• While rare, the test might trigger a heart attack or stroke.
Trans-esophageal Echocardiography Risks
A possible risk of the echocardiogram when the tube is placed into your
esophagus is:
• a tear or poking of your esophagus, the tube connecting your mouth to your
stomach. This tear could cause bleeding or infection that is possibly life
threatening, and in some cases may need surgery for repair. These risks are
very uncommon.
*
Risks of Antiplatelet Médicine
The antiplatelet medicine, clopidogrel, is often used with metal implants to
reduce the chance of getting a blood clot. If you have any allergies to
antiplatelet medications let your study team know. Antiplatelet medicines like
clopidogrel and Plavix have known risks.
Clopidogrel can cause bleeding problems, headaches, dizziness, pain, or
discomfort. Any doctor you see must know about this medicine. It is common
for a physician to stop clopidogrel before invasive procedures or surgery.
Less common risks include bruises, swelling, blood in your urine or stool, or
stools that look like coffee grounds.
A rare but serious risk is Thrombotic Thrombocytopenic Purpura (TTP), an
illness which has fever, noticeable blackish areas on your arms or legs, and
bleeding gums or nose. See you doctor immediately if you are concerned about
this.
Use of dual antiplatelet therapy, the combined use of clopidogrel and aspirin,
increases your risks for life threatening bleeding such as intracranial
hemorrhage (brain bleed) or hemorrhagic (bleeding) stroke.
Exercise Testing Risks
To decrease the risks in exercise testing, trained medical people will be
present. In addition, you will have your heart rate, blood pressure and your
rate of perceived exertion checked throughout the testing.
The peak oxygen test can make you tired, light-headed, severe shortness of
breath, from walking on the treadmill or pedaling the exercise bike.
After the test you may have muscle soreness, irregular heartbeat, chest pain.
While rare, the test might trigger a heart attack or stroke.
Blood Draw Risks
There are some side effects that can happen when you have blood drawn. This
includes bleeding, fainting or feeling light-headed, blood pooling under the
skin, infection (a slight risk any time the skin is broken).
HealthPatchMD® Risks
Take care when shaving and let your study doctor know if you have allergies to
adhesives such as those on BandAids.
Chest hair will need to be shaved which poses the risk of a skin cut.
Skin irritation or redness may occur from wearing the patch. When you remove
the patch you may feel pulling on your skin, like a strong Band-Aid®. Use the
remover swab to reduce irritation.
Allergic reactions to the adhesive are also possible.
*
Cardiac MRI Risks
The magnetic resonance imaging (MRI) machine uses a strong magnet to take
pictures of your heart. The MRI magnet may cause any metal in your body to
move. You will be asked many questions before the MRI to make sure you can have
an MRI. People with certain implanted metal devices such as pacemakers or other
internal metal objects like surgical plates, screws, or wire mesh need special
attention before the MRI goes on.
Pregnant Women
Fertile woman of childbearing age are not authorized to take part of this
clinical trial. The invasive procedure and associated imaging and medications
may have unforeseeable risks to your embryo or foetus.
Possible benefits to subjects who are in the treatment group of the study may
include the following:
• Less shortness of breath
• Less hospitalizations and/or hospital days
• Less emergency room visits
• Less in medication
• Better exercise tolerance
• Better quality of life
• Better life expectancy
Possible benefits to patients in the control group of the study may include the
following:
• Your medication will be carefully checked
• The procedure could detect heart defects that might have been missed in other
examinations. This includes a patent foramen ovale (PFO), which is a hole in
the heart that didn't close normally after birth, or small atrial septal
defects (ASD).
• The procedure could show clotting of blood in the heart, which would need
treatment or more exams.
The results of this study may help people with heart failure in the future. It
may help to further assess the safety and effectiveness of the IASD implant in
treating the signs and symptoms of patients with a condition like yours. The
information might also be used to develop new treatments for patients with
similar conditions.
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Listed location countries
Age
Inclusion criteria
1. Chronic symptomatic heart failure (HF) documented by the following:
a. Symptoms of HF requiring current treatment with diuretics for >= 30 days and
b. New York Heart Association (NYHA) class II if a prior history of > NYHA
class II; or NYHA class III, or ambulatory NYHA 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; AND
c. >= 1 HF hospital admission (with HF as the primary, or secondary diagnosis);
or treatment with intravenous (IV), or the need for intensification of oral
diuresis for HF in a healthcare facility , within the 12 months prior to study
entry; OR an NT-pro BNP value > 150 pg./ml in normal sinus rhythm, > 450 pg./ml
in atrial fibrillation, or a BNP value > 50 pg./ml in normal sinus rhythm, >
150 pg./ml in atrial fibrillation within the past 6 months.
2. Ongoing stable GDMT HF management and management of potential comorbidities
according to the 2017 ACC/AHA Guidelines for the management of Heart Failure,
with no significant changes (>100% increase or 50% decrease), excluding
diuretic dose changes, for a minimum of 4 weeks prior to enrollment which is
expected to be maintained for 6 months.Stable management includes a minimum
period of 4 weeks post hospitalization for any cause, including treatment with
IV diuretics.
3. Age >= 40 years old
4. Site determined echocardiographic LV ejection fraction >=40% within the past
6 months, without documented ejection fraction <30% in the 5 years prior to
study entry.
5. Site determined elevated PCWP with a gradient compared to right atrial
pressure (RAP) documented by:
End-expiratory PCWP during supine ergometer exercise >= 25mm Hg, and greater
than RAP by >= 5 mm Hg.
6. Site determined echocardiographic evidence of diastolic dysfunction
documented by one or more of the following:
a. LA diameter > 4 cm; or
b. Diastolic LA volume > 50, or LA volume index > 28 ml/m2 or
c. Lateral e* < 10 cm/s; or
d. Septal e* < 8 cm/s; or
e. Lateral E/e* > 10 ; or
f. Septal E/e* > 15
7. Subject has been informed of the nature of the study, agrees to its
provisions and has provided written informed consent, approved by the IRB or EC
8. Subject is willing to comply with clinical investigation procedures and
agrees to return for all required follow-up visits, tests, and exams
9. Trans-septal catheterization and femoral vein access to the right atrium is
determined to be feasible by site interventional cardiology investigator.
Exclusion criteria
1. MI and/or percutaneous cardiac intervention within past 3 months; CABG in
past 3 months, or current indication for coronary revascularization; AVR
(surgical AVR or TAVR) within the past 12 months or a planned cardiac
interventions in the 3 months following enrollment.
2. Cardiac resynchronization therapy initiated within the past 6 months
3. Advanced heart failure defined as one or more of the below:
a. ACC/AHA/ESC Stage D heart failure, Non-ambulatory NYHA Class IV HF;
b. Cardiac index < 2.0 L/min/m2
c. Inotropic infusion (continuous or intermittent) for EF < 40% within the past
6 months
d. Patient is on the cardiac transplant waiting list
4. Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk
test > 600m
5. The patient has verified that the ability to walk 6 minutes is limited
primarily by joint, foot, leg, hip or back pain; unsteadiness or dizziness or
lifestyle and not by shortness of breath and/or fatigue and/or chest pain.
6. Unwilling or unable (per PhysIQ protocol) to wear telemonitoring patch,
unless cell-phone based monitoring device is not available in that region
7. Known clinically significant un-revascularized coronary artery disease,
defined as: epi-cardial coronary artery stenosis with angina or other evidence
of ongoing active coronary ischemia.
8. History of stroke, transient ischemic attack (TIA), deep vein thrombosis
(DVT), or pulmonary emboli within the past 6 months
9. Known clinically significant untreated carotid artery stenosis likely to
require intervention.
10. Presence of hemodynamically significant valve disease assessed by the site
cardiologist and defined as:
a. Mitral valve disease defined as grade >= 3+ MR or > mild MS OR
b. Tricuspid valve regurgitation defined as grade >= 2+ TR OR
c. Aortic valve disease defined as >= 2+ AR or > moderate AS
11. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy,
constrictive pericarditis, cardiac amyloidosis or other infiltrative
cardiomyopathy (e.g. hemochromatosis, sarcoidosis)
12. Subject is contraindicated to receive either dual antiplatelet therapy or
an oral anticoagulant;); or has a documented coagulopathy
13. Atrial fibrillation with resting HR > 100 BPM
14. Resting arterial oxygen saturation < 95% on room air
15. Significant hepatic impairment defined as 3X upper limit of normal of
transaminases, total bilirubin, or alkaline phosphatase
16. Right ventricular dysfunction, assessed by the site cardiologist and
defined as
a. More than mild RV dysfunction as estimated by TTE; OR
b. TAPSE < 1.4 cm; OR
c. RV size >= LV size as estimated by TTE; OR
d. Ultrasound or clinical evidence of congestive hepatopathy; OR
e. Evidence of RV dysfunction defined by TTE as an RV fractional area change <
35%;
17. Resting RAP > 14 mmHg
18. Evidence of significant pulmonary hypertension defined as PVR > 3.5 Wood
units at rest or peak exercise
19. Chronic pulmonary disease requiring continuous home oxygen, OR significant
chronic pulmonary disease defined as FEV1 <1L.
20. Hemoglobin <10 g/dl
21. Currently participating in an investigational drug or device study that
would interfere with the conduct or results of this study. Note: trials
requiring extended follow-up for products that were investigational but have
since become commercially available are not considered investigational
22. Life expectancy less than 12 months for known non-cardiovascular reasons
23. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
24. Known or suspected allergy to nickel
25. Women of child bearing potential
26. Currently requiring dialysis; or estimated-GFR <25ml/min/1.73 m2 by CKD-Epi
equation
27. Systolic blood pressure >170 mm Hg.at screening
28. Subjects with existing or surgical closed( with a patch)atrial septal
defects. Subjects with a patent foramen ovale (PFO), who meet PCWP criteria
despite the PFO, are not excluded.
29. Subjects on significant immunosuppressive treatment or on systemic steroid
treatment (>10 mg prednisone/day).
30. Severe obstructive sleep apnea not treated with CPAP or other measures
31. Severe depression and/or anxiety
32. In the opinion of the investigator, the subject is not an appropriate
candidate for the study
33. BMI >45. BMI 40 - 45 is also excluded unless in the opinion of the
investigator, vascular access can be obtained safely.
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 | NCT03088033 |
| CCMO | NL61895.042.17 |