VisONE Heart Failure Study: Pilot

VisONE Pilot Study of Chronic Asymptomatic Diaphragmatic Stimulation for Patients With Symptomatic Heart Failure, Reduced Ejection Fraction and Preserved Ventricular Synchrony

The VisONE HF pilot is a feasibility pilot for evaluating the benefits and risks of chronically delivering Asymptomatic Diaphragmatic Stimulation in medical refractory heart failure patients using the VisONE™ implantable system for 12 months.

Study Overview

• Status: Completed
• Conditions: Heart Failure With Reduced Ejection Fraction, HFrEF
• Intervention / Treatment: Device: VisONE ADS

Detailed Description

This 12 month study is intended to validate the early benefits observed with Asymptomatic Diaphragmatic Stimulation (ADS) as a primary form of heart failure therapy with low rates and severity of adverse effects. Medical refractory symptomatic heart failure patients with reduced ejection fraction and no evidence of arrhythmias or ventricular dysynchrony will undergo laparoscopic implantation of the VisONE™ implantable system comprised of a pulse generator and two leads, programmed to deliver cardiac-gaited diaphragmatic stimulation pulses at asymptomatic outputs. Patients will be followed in pre-specified durations of 1,3,6 and 12-months using a series of evaluations of hemodynamic, echocardiographic, heart failure status, diaphragmatic function, implanted system data and standard safety measures including adverse events, for comparison with their baseline values. The results are intended to be used for designing a subsequent larger study for performing statistical power calculations.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Georgia
  • Tbilisi, Georgia, 0159
    • Tbilisi Heart and Vascular Clinic
• Ukraine
  • Kiev, Ukraine
    • Kyiv City Heart Center
  • Kyiv, Ukraine
    • Amosov National Institute of cardiovascular surgery

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• NYHA class II/III medical refractory despite guideline indicated heart failure medications
• Sinus rhythm with <10% ectopy
• EF ≤ 35%
• NT-proBNP > 500 (250 if on loop diuretics)

Exclusion Criteria

• 6MHW >500 m or < 200 m
• Resting HR > 140 bpm
• SBP <80 mmHg or > 170 mmHg
• Serum creatine > 2.5 mg/dL
• Ventricular dyssynchrony by ECG with QRS ≥ 140ms
• Unstable angina, AMI, CABG, PTCA, CVA/TIA, persistent AF, NSVT, sustained VT or VF, or DCCV within 3 months
• Intermittent inotropic drug treatment
• Existing pacemaker or indications for a pacemaker
• Severe primary pulmonary disease including pulmonary arterial hypertension or severe COPD, or other respiratory or lung diseases where FEV < 50% or any condition with severe diaphragmatic dysfunction
• Previous open laparotomy within 1 year or contraindications to laparoscopy, as determined by implanting physician
• Known or active intra-abdominal infections, or known intra-abdominal pathology
• Previous thoracic or abdominal organ transplant, transplant waiting list
• Pregnancy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VisONE ADS; Patients implanted with a VisONE stimulator and leads for receiving continual Synchronized Diaphragmatic Stimulation	Device: VisONE ADS; VisONE stimulator and leads for delivering continual Synchronized Diaphragmatic Stimulation; Other Names: Synchronized Diaphragmatic Stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from serious complications or adverse events during procedural recovery and acute therapy	The following serious complications and adverse events will be analyzed for their rate and severity and compared to other implantable device systems; Excessive procedural or implanted system morbidity; Procedural or implanted system events resulting in unscheduled patient hospitalizations and surgical intervention; Incidences resulting in physician choice to permanently discontinue therapy	after 3 months of therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Freedom from complications or adverse events during chronic therapy	The following adverse events will be analyzed for their rate and severity and compared to other implantable device systems; Procedural or implanted system events resulting in adverse patient symptoms; Degradation of respiratory function by spirometer measures associated with procedure or implanted system; Adverse events due to procedural or implanted system complications correctable by non re-operative means including system reprogramming or other readjustments	after 3 and 12 months of therapy
Freedom from serious complications or adverse events during chronic therapy	The following serious complications and adverse events will be analyzed for their rate and severity and compared to other implantable device systems; Excessive procedural or implanted system morbidity; Procedural or implanted system events resulting in unscheduled patient hospitalizations and surgical intervention; Incidences resulting in physician choice to permanently discontinue therapy	after 12 months of therapy

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical composite of heart failure and cardiac function	The following outcomes will be analyzed determine the potential therapeutic impact on clinical heart failure management; NT Pro-BNP blood levels to assess heart failure status; Improvements to cardiac output, stroke volume or left ventricular filling; Improvements to left ventricular volumes or ejection fraction; Improvements to heart failure status, 6 minute hall walk, or assessment by heart failure questionnaire	after 0, 1, 3, 6 and 12 months of therapy

Collaborators and Investigators

• Sponsor: VisCardia Inc.
• Collaborators: University Hospital, Zürich; University of Glasgow; Clinical Accelerator Ltd.; Stiftung für Herz-und Kreislaufkrankheiten
• Investigators: Principal Investigator: Vitaly Demyanchuk, M.D. Ph.D., Kyiv City Heart Center; Principal Investigator: Rudenko Vladimirovich, M.D., Amosov National Institute of cardiovascular surgery; Principal Investigator: Tamaz Shaburishvil, M.D., Tbilisi Heart and Vascular Clinic

Publications and helpful links

General Publications

• Beeler R, Schoenenberger AW, Bauer P, Kobza R, Bergner M, Mueller X, Schlaepfer R, Zuber M, Erne S, Erne P. Improvement of cardiac function with device-based diaphragmatic stimulation in chronic heart failure patients: the randomized, open-label, crossover Epiphrenic II Pilot Trial. Eur J Heart Fail. 2014 Mar;16(3):342-9. doi: 10.1002/ejhf.20. Epub 2013 Dec 6.
• Roos M, Kobza R, Jamshidi P, Bauer P, Resink T, Schlaepfer R, Stulz P, Zuber M, Erne P. Improved cardiac performance through pacing-induced diaphragmatic stimulation: a novel electrophysiological approach in heart failure management? Europace. 2009 Feb;11(2):191-9. doi: 10.1093/europace/eun377.
• Jorbenadze A, Shaburishvili N, Mirro M, Zuber M, Erne P, Shaburishvili T. First-In-Human Visone Heart Failure Study: Asymptomatic Diaphragmatic Stimulation For Chronic Heart Failure With Reduced Ejection Fraction: Case Report. Journal of the American College of Cardiology. 2020;75(11) Supplement 1

Helpful Links

• Proof of concept therapeutic feasibility study of chronic ADS in post CABG heart failure patients

Study record dates

Study Major Dates

• Study Start (Actual): July 25, 2018
• Primary Completion (Actual): December 12, 2019
• Study Completion (Actual): December 12, 2019

Study Registration Dates

• First Submitted: March 16, 2018
• First Submitted That Met QC Criteria: March 25, 2018
• First Posted (Actual): April 2, 2018

Study Record Updates

• Last Update Posted (Actual): May 20, 2020
• Last Update Submitted That Met QC Criteria: May 18, 2020
• Last Verified: May 1, 2020

More Information

Terms related to this study

• Keywords: Implantable Heart Failure Device Therapy; Asymptomatic Diaphragmatic Stimulation
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: VisCardia H01_17

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No