The primary objective of this clinical trial is to further evaluate the clinical efficacy of the Corvia Atrial Shunt in symptomatic heart failure patients with a left ventricular ejection fraction (LVEF) >= 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) total rate (first plus recurrent)
per patient year of heart failure (HF) admissions or healthcare facility visits
for IV diuresis or urgent visits with intensification of oral diuresis for HF
through 24 months follow-up, analyzed when the last patient completes 12 months
follow-up, and time-to-first HF event; and (b) change from baseline KCCQ total
summary score at 12 months. Heart failure events reported by investigators will
be adjudicated to the primary endpoint by the CEC. Evaluated through Bayesian
technique which borrows treatment effect from the RCT II clinical trial.
Primary Analysis Bayesian statistical analysis of the primary endpoint:
Treatment groups from the Modified Intention to Treat (MITT) population will be
compared with a Bayesian cumulative logistic proportional odds regression. The
analysis utilizes pairwise comparisons from the Finkelstein-Schoenfeld test
framework to compare patient outcomes on the primary endpoint. The testing
hierarchy is the HF event rate, the time to first HF event followed by the KCCQ
component. For each pairwise comparison, patients are assigned a 1, 0, -1 if
the patient won, tied, or lost the comparison, respectively. The *F-S score*
for each patient is calculated as the sum of
their pairwise comparison outcomes.
The primary analysis is a Bayesian cumulative logistic proportional odds
regression analysis on the F-S scores that facilitates borrowing of information
(30%, fixed) on the treatment effect from the previous REDUCE LAP-HF RCT II
study within a responder subgroup. The treatment effect will be estimated as
the increase or decrease in the odds (odds ratio; OR) of having more wins in
the pairwise F-S comparisons in the active treatment group compared to the
control group. The null hypothesis will be tested based on the posterior
probability that the OR is greater than 1. Significance will be declared if the
posterior probability the OR > 1 is greater than 0.975.
Secondary outcome
Major Secondary Endpoint: The major secondary endpoint is the incidence of and
time-to-cardiovascular mortality through 12 months.
Statistical Analysis Secondary Outcome Measures: Listings and descriptive
statistics will be provided and compared for similarity with the
same measures from RCT II.
Background summary
The Corvia Atrial Shunt System is indicated for the improvement in quality of
life and reduction of heart failure related symptoms and events in patients
with heart failure with preserved (HFpEF) or mildly reduced ejection fraction
(HFmrEF) with elevated left atrial pressures, without latent pulmonary vascular
disease and without a cardiac rhythm device, who remain symptomatic despite
standard GDMT. The Corvia Atrial Shunt System / InterAtrial Shunt Device
(IASD®) System II bears the CE Mark for medical devices in Europe.
Study objective
The primary objective of this clinical trial is to further evaluate the
clinical efficacy of the Corvia Atrial Shunt in symptomatic heart failure
patients with a left ventricular ejection fraction (LVEF) >= 40%, and elevated
left sided filling pressures despite standard Guideline-Directed Medical
Therapy (GDMT); and to confirm the treatment effect observed in the responder
group of the REDUCE LAP-HF Randomized Trial II. (Corvia protocol 1601).
Study design
Multicenter, Prospective, Randomized, Sham Controlled, Double Blinded Clinical
Trial, with 1:1 randomization
Patients are consented to participate, screened against non-invasive
eligibility criteria. Baseline characteristics, demographic, medical history,
heart failure medication, echocardiogram, and relevant laboratory data
summarized in the Potential Participant Trial Eligibility Committee Evaluation
Form, are reviewed by the Trial Eligibility Committee ( TEC) to
1) approve the participant for hemodynamic evaluation;
2) to request additional information; or
3) to exclude the participant from further participation the RESPONDER-HF
trial.
If the patient does not qualify, then the patient becomes a screen failed
patient and is not scheduled for the exercise hemodynamic study and potential
randomization.
If the participant is approved, they are scheduled for hemodynamic evaluation
including right heart catheterization with hemodynamic measurements at rest and
during supine bicycle exercise. Hemodynamically eligible patients will then be
blinded and sedated; There will a soft cloth placed to cover the eyes and ear
buds used which will be connected to a music player. In addition screens will
be used to prevent participants from viewing the imaging screens, which
indicate the presence or absence of the device.
All patients will have femoral venous access and will undergo a brief
intracardiac echocardiography (ICE) or transesophageal echocardiography (TEE)
exam for anatomic suitability. Eligible patients are then randomized to the
treatment or control group. Patients randomized to the control group receive
additional cardiac imaging and end their intervention with removal of devices.
Patients in the treatment arm will undergo an echo
and fluoroscopically guided transseptal puncture and Corvia Atrial Shunt
implant procedure. If a previously unknown protocol exclusion is discovered
during the index procedure, and prior to the initiation of transseptal
puncture, the participant is unblinded, followed for 30 days and then exits the
study. All patients receive a physical exam and study medications by an
unblinded physician or nurse prior to discharge.
Physicians responsible for managing patient care, research staff involved in
conducting follow-up evaluations, and the hemodynamic core laboratory will be
blinded to study arm assignment, including baseline hemodynamic data until the
patient is unblinded.
Randomized patients will be followed for 30 days, 3, 6, 12, 18 and 24 months
and annually for 5 years after the index procedure. In-person visits will take
place for the first 24 months. Telephone follow-up and medical chart review
will be conducted for years 3-5
Patients and blinded staff will be unblinded following the 24-month follow-up
visit.
Patients randomized to the control arm may be offered an opportunity to
cross-over to the treatment arm at after 24 months provided patient selection
criteria are met at that time.
Crossover patients will then be followed in person for 30 days and 6 and 12
months, and by telephone and chart review annually for 5 years after the
crossover procedure.
Independent CEC, DSMB, and core laboratories will be utilized during this
trial.
Study burden and risks
Subjects participation in the study will last up to 5-7 years.
The following is out of standard care:
Blood sample collection,
electrocardiogram,
echocardiography,
6-minute walk test,
Invasive exercise hemodynamic evaluation,
Questionnaires and Telephone Follow-Up
Risks associated:
Complications associated with implantation of the Corvia Atrial Shunt and
similar procedures in which implants are placed on the atrial septum.
Participation in the study carries additional assessments and imaging above the
standard of care.
All other study-specific assessments are clinic and physical assessments that
would be within the range of standard follow-up of patients with a this medical
history. Additional HF symptom and quality of life assessments with surveys and
walking tests.
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. Subjects can still receive the same device treatment outside of the
study. 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 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 Highwood Drive Suite 300
Tewksbury, MA 01876
US
One Highwood Drive Suite 300
Tewksbury, MA 01876
US
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 if tolerated for >=
30 days AND
b. New York Heart Association (NYHA) class II with prior history of >class II;
OR NYHA class III, or ambulatory
NYHA class IV symptoms; AND
c. >= 1 HF hospital admission (with HF as the primary, or secondary diagnosis);
or treatment with intravenous (IV) diuretics; or intensification of oral
diuresis 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 comorbidities according
to the 2022 ACC/AHA Guidelines for the Management of Heart Failure. Stable
management includes a minimum period of 4 weeks post-hospitalization for any
cause, including treatment with IV diuretics.
3. Site determined echocardiographic LV ejection fraction >= 40% within the past
6 months, without documented ejection fraction < 30% in the 5 years prior.
4. 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/m 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
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. Resting RAP <= 14 mmHg
7. Site determined hemodynamic evidence of peak exercise PVR < 1.75 Wood units
[NEW
inclusion criterion]
8. Age >= 40 years old
9. Participant 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
10. Participant is willing to comply with clinical investigation procedures and
agrees to return for all required follow-up visits, tests, and exams
11. Transseptal catheterization and femoral vein access to the right atrium is
determined to be feasible by site interventional cardiology investigator.
Exclusion criteria
1. 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.
2. Inability to perform 6 minute walk test (distance < 50 m), OR 6 minute walk
test > 600m
3. 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).
4. Right ventricular dysfunction, assessed by the site cardiologist and defined
as one or more of the following:
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%.
5. Any implanted cardiac rhythm device [NEW exclusion criterion]
6. Structural heart repair AVR or MVR (surgical or percutaneous) within the
past 12 months; planned valve intervention in the next 3 months, or presence
of hemodynamically significant valve disease as assessed by the site
cardiologist and defined as:
a. Mitral valve disease grade >= 3+ MR or > mild MS; OR
b. Tricuspid valve regurgitation grade >= 2+ TR; OR
c. Aortic valve disease >= 2+ AR or > moderate AS.
7. Echocardiographic evidence of intra-cardiac mass, thrombus or vegetation
8. Participants with existing or surgically closed (with a patch) atrial septal
defects.
Participants with a patent foramen ovale (PFO), who meet PCWP criteria despite
the PFO, are not excluded.
9. MI and/or percutaneous cardiac intervention within past 3 months; CABG in
past 3 months or any planned cardiac interventions in the 3 months following
enrollment.
10. Known clinically significant un-revascularized coronary artery disease,
defined as:
coronary artery stenosis with angina or other evidence of ongoing active
coronary ischemia.
11. Known clinically significant untreated carotid artery stenosis likely to
require intervention.
12. Atrial fibrillation with resting HR > 100 BPM
13. Hypertrophic obstructive cardiomyopathy, restrictive cardiomyopathy,
constrictive pericarditis, cardiac amyloidosis or infiltrative cardiomyopathy
(e.g. hemochromatosis sarcoidosis)
14. History of stroke, transient ischemic attack (TIA), deep vein thrombosis
(DVT), or pulmonary emboli within the past 6 months.
15. Participant is contraindicated to receive either dual antiplatelet therapy,
or an oral anticoagulant; or has a documented coagulopathy
16. Anemia with Hemoglobin < 10 g/dl
17. Chronic pulmonary disease requiring continuous home oxygen, OR significant
chronic pulmonary disease defined as FEV1 <1L.
18. Resting arterial oxygen saturation < 95% on room air, <93% when residing at
high altitude
19. Currently requiring dialysis; or estimated GFR < 25ml/min/1.73 m2 by
CKD-Epi equation
20. Systolic blood pressure > 170 mm Hg at screening
21. Significant hepatic impairment defined as 3X upper limit of normal of
transaminases, total bilirubin, or alkaline phosphatase
22. Participants on significant immunosuppressive treatment or on systemic
steroid treatment
23. Life expectancy less than 12 months for known non-cardiovascular reasons
24. Known hypersensitivity to nickel or titanium
25. Women of childbearing potential
26. Severe obstructive sleep apnea not treated with CPAP or other measures
27. BMI > 45; BMI 40 - 45 is also excluded unless in the opinion of the
investigator, vascular access can be obtained safely.
28. Severe depression and/or anxiety
29. 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
30. In the opinion of the investigator, the Participant is not an appropriate
candidate for the study
31. No patients who are unable to give consent will be included in the clinical
trial
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 | NCT05425459 |
| CCMO | NL82526.042.22 |