Heart Failure With Reduced Ejection Fraction
Conditions
Keywords
Heart Failure, Heart Disease, Synchronized Diaphragmatic Stimulation, Implantable Heart Failure Device Therapy
Brief summary
RECOVER HF is a clinical study designed to evaluate the safety and efficacy of Synchronized Diaphragmatic Stimulation delivered using the VisONE System in the treatment of patients with heart failure.
Detailed description
Symptomatic Diaphragmatic Stimulation (SDS) is a novel extra-cardiac device for patients who have symptomatic heart failure. Elevated intracardiac pressures are the hallmark of heart failure (HF) and a key pathological driver of disease progression and limited exertional capacity. The degree of cardiac pressure elevation is determined by preload, afterload, and pericardial restraint. The pericardium restrains the heart, and the degree of restraint is determined by the pericardial structure itself and the intrathoracic pressure. This aspect of HF pathophysiology is among the fundamental drivers behind the SDS therapy concept. SDS induces a temporal modulation of intrathoracic pressure.. When synchronized with the cardiac cycle, SDS may improve cardiac filling, cardiovascular pressure conditions, and cardiac performance RECOVER HF is a prospective, randomized, doubled-blinded study of Synchronized Diaphragmatic Stimulation (SDS) delivered in an imperceptible manner in subjects with heart failure defined as New York Heart Association (NYHA) functional class II/III, left-ventricular ejection fraction (LVEF) \<=40%, and QRS duration \<=130ms despite receiving the appropriate heart failure guideline directed medical therapy (GDMT). All subjects will receive an implanted VisONE System. Two-weeks post implant subjects will be randomized in a 1:1 ratio into a SDS therapy active or control (SDS therapy inactive) arm with both arms receiving GDMT. At 6 months the control arm will have SDS therapy activated with all patients receiving therapy and GDMT throughout the remainder of the study period. The study will be conducted at up to 30 investigational sites in the United States and several outside the U.S. These centers will enroll subjects with the goal of randomizing approximately 270 subjects who meet the entry criteria.
Interventions
Implantable Pulse Generator system providing cardiac-gaited stimulation of the diaphragm and thereby influence cardiovascular properties relevant in heart failure.
Sponsors
VisCardia Inc.
Clinical Accelerator
Duke Clinical Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Investigator and care provider blinded to device programming, therapy imperceptible to patient, data analysis through independent entities
Intervention model description
Initial randomization into Control and Therapy arms for 6 month primary endpoints, afterwards crossover of Control arm into Therapy arm for 12 month secondary endpoints.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* NYHA classes II/III on optimal Guideline Directed Medical Therapy (GDMT) * QRS duration ≤ 130 ms * EF≤ 40%
Exclusion criteria
* Baseline 6 minute walk test \> 500 meters or \< 200 meters * NT-proBNP\< 250 if on loop diuretics, or NT-proBNP \< 500 if not on loop diuretics * Supine resting heart rate \> 140 bpm * Systolic blood pressure \< 80 mmHg or \> 170 mmHg * Serum creatinine \> 2.5 mg/dL * Serum hepatic function 3x ULN * Any of the following within the previous 3 months: unstable angina, AMI, CABG, PTCA, CVA/TIA, persistent AF (\> 24 hours), symptomatic NSVT or DCCV * Any inotropic drug treatment within the previous 3 months * Bradycardia (heart rate \< 50 beats/min), atrial arrhythmias with rates \> 100 beats/min, sustained ventricular tachycardia or frequent ventricular ectopy \>10% present during screening * Significant uncontrolled symptomatic bradyarrhythmia, atrial fibrillation, unstable ventricular arrhythmias or frequent ventricular ectopy \> 10% documented within the previous 3 months * Reversible non-ischemic cardiomyopathy * Valvular disease requiring intervention within the next 12 months or presence of significant valve disease as determined by the site cardiologist as: 1. Greater than mild mitral valve stenosis 2. Greater than moderate mitral valve regurgitation 3. Greater than mild tricuspid valve stenosis 4. Greater than moderate-severe tricuspid valve regurgitation 5. Greater than moderate aortic stenosis 6. Greater than moderate aortic regurgitation 7. Greater than mild-moderate pulmonic stenosis 8. Greater than moderate pulmonic regurgitation * Severe primary pulmonary disease, including pulmonary arterial hypertension. PAP sys \>70 mmHg at rest * Severe COPD, other respiratory or lung diseases where FEV \< 50% * Presence of more than small pleural effusion or history of pleural drainage within the previous 6 months * Known history of diaphragmatic paralysis or suspicion confirmed by unilateral or bilateral elevation of the diaphragm on chest x-ray * Pericardial disease * Diabetic neuropathy * Existing diaphragmatic stimulation for respiration assist * Present LVAD, Baroreflex Activation Therapy, Cardiac Contractility Modulation or interatrial shunt devices; temporary mechanical cardiac assist devices (current or within the previous 3 months); or CRT that is indicated or implanted and functional * Contraindications to laparoscopic access to the diaphragm, as determined by the implanting physician * Known intra-abdominal pathology which could increase the risk of laparoscopic access to the diaphragm. * Previous open laparotomy within 1 year * Previous thoracic or abdominal organ transplant * Drug induced immuno-suppression * Body mass index \> 40 * Enrollment in a concurrent investigation / clinical study * Having a life expectancy of \<1 year due to any condition * Pregnant or planning a pregnancy during the study period * Known allergies to implantable device materials * History of systemic infection requiring the use of intravenous antibiotics within the previous 3 months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Left ventricular End-Systolic Volume (LVESV) | 6 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger percent improvement in LVESV at 6 months post-randomization from baseline than medical management alone. |
| Six Minute Hall Walk (6MHW) | 6 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger improvement in 6MHW at 6 months post-randomization from baseline than medical management alone. |
| Minnesota Living with Heart Failure quality of Life Score (MLWHF QOL) | 6 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger improvement in MLWHF QOL at 6 months post-randomization from baseline than medical management alone. |
| Major Adverse Respiratory and Cardiovascular Events (MARCE) | 6 months | To demonstrate the safety of the VisONE System by analyzing Major Adverse Respiratory and Cardiovascular Events (MARCE) occurring within 6 months post implant for the rate, severity and association with the device or procedure (goal \>70% freedom): * Cardiovascular Death * Stroke * Cardiac Arrest * Interaction with cardiac rhythm device requiring permanent termination of SDS therapy * Acute Heart Failure Decompensation * Infection requiring device/lead explant * Diaphragmatic dysfunction leading to a clinically significant reduction is respiratory function * Inadequate SDS therapy delivery requiring surgical intervention * Injury to abdominal organs requiring surgical intervention * Pneumothorax * Hemothorax |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Left Ventricular Ejection Fraction (LVEF) | 6 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger improvement in LVEF at 6 months post-randomization from baseline than medical management alone. |
| N-Terminal Pro Brain Natriuretic Peptide (NT-proBNP) | 6 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger reduction in NT-proBNP (log-10 transformed) at 6 months post-randomization from baseline than medical management alone. |
| Left ventricular End-Systolic Volume (LVESV) | 12 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger percent improvement in LVESV at 12 months post-randomization from baseline than medical management alone. |
| Six Minute Hall Walk (6MHW) | 12 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger improvement in 6MHW at 12 months post-randomization from baseline than medical management alone. |
| Minnesota Living with Heart Failure quality of Life Score (MLWHF QOL) | 12 months | To demonstrate that treatment with the VisONE System (SDS) plus GDMT results in a larger improvement in MLWHF QOL at 12 months post-randomization from baseline than medical management alone. |
Countries
Georgia, United States
Contacts
CONTACTCalvin Flowers
CONTACTJoelle Duker
PRINCIPAL_INVESTIGATORLee R Goldberg, MD
University of Pennsylvania
Outcome results
None listed