Clinical trial NCT06552637: Synchronized Diaphragmatic Stimulation in Symptomatic Heart Failure
Official title: RECOVER-HF - RandomizEd, Multi-Center, Double-Blinded Study of SynchrOnized Diaphragmatic Stimulation (SDS) for ImproVEment of Symptomatic Reduced Ejection Fraction Heart Failure
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Heart Failure With Reduced Ejection Fraction
Keywords: Heart Failure
Heart Disease
Synchronized Diaphragmatic Stimulation
Implantable Heart Failure Device Therapy
Lead sponsor: VisCardia Inc.
Sponsor class: INDUSTRY
Collaborators: name: Clinical Accelerator
name: Duke Clinical Research Institute
First posted: 2024-08-14
Enrollment: 270
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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
* Unstable angina, AMI, CABG, PTCA, CVA/TIA, persistent AF, NSVT or DCCV within 3 months
* Intermittent IV inotropic drug treatment
* 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 bradyarrhythmias, atrial fibrillation, unstable ventricular arrhythmias or frequent ventricular ectopy \> 10% documented within the previous 3 months
* Reversible non-ischemic cardiomyopathy
* Primary valvular disease
* Severe primary pulmonary disease, including pulmonary arterial hypertension. PAP sys \>70 mmHg at rest
* Severe COPD, other respiratory or lung diseases where FEV \< 50%
* Pericardial disease
* Diabetic neuropathy
* Existing diaphragmatic stimulation for respiration assist
* LVAD or other mechanical cardiac assist devices
* 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
* Recent history of systemic infections

Primary outcomes:
measure: Left ventricular End-Systolic Volume (LVESV)
timeFrame: 6 months
measure: Six Minute Hall Walk (6MHW)
timeFrame: 6 months
measure: Minnesota Living with Heart Failure quality of Life Score (MLWHF QOL)
timeFrame: 6 months
measure: Major Adverse Respiratory and Cardiovascular Events (MARCE)
timeFrame: 6 months
Secondary outcomes:
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 6 months
measure: N-Terminal Pro Brain Natriuretic Peptide (NT-proBNP)
timeFrame: 6 months
measure: Left ventricular End-Systolic Volume (LVESV)
timeFrame: 12 months
measure: Six Minute Hall Walk (6MHW)
timeFrame: 12 months
measure: Minnesota Living with Heart Failure quality of Life Score (MLWHF QOL)
timeFrame: 12 months
measure: Left Ventricular Ejection Fraction (LVEF)
timeFrame: 12 months
measure: N-Terminal Pro Brain Natriuretic Peptide (NT-proBNP)
timeFrame: 12 months
Other outcomes:
Locations:
Study officials:
affiliation: University of Pennsylvania
name: Lee R Goldberg, MD
role: PRINCIPAL_INVESTIGATOR
References: