Baroreflex Activation Therapy for Heart Failure

Heart Failure Clinical Trial

— BeAT-HF  

Official title:

Barostim Neo® - Baroreflex Activation Therapy® for Heart Failure

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02627196
• Other study ID #: 360043-001
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 19, 2016
• Est. completion date: December 2023

Study information

• Verified date: January 2023
• Source: CVRx, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this clinical trial (NCT02627196) is to develop valid scientific evidence for safety and effectiveness of Baroreflex Activation Therapy with the BAROSTIM NEO System in subjects with heart failure, defined as New York Heart Association (NYHA) functional Class III, left ventricular ejection fraction (LVEF) ≤ 35% and NT-proBNP<1600 pg/ml despite being treated with the appropriate heart failure guideline directed therapy, excluding subjects eligible for or actively receiving Cardiac Resynchronization Therapy (CRT).

The total trial duration is anticipated to be approximately 5 years; however, the duration of an individual subject enrollment will depend on when he or she entered the trial.

Description:

The BAROSTIM NEO - Baroreflex Activation Therapy for Heart Failure is a prospective, randomized trial in subjects with reduced ejection fraction heart failure. Subjects will be randomized in a 1:1 ratio to receive Barostim Activation Therapy with an implanted BAROSTIM NEO System in addition to medical management or to receive medical management alone (no device implant). The trial will be conducted at up to 120 investigational centers in the U.S. and up to 20 investigational centers outside the U.S. These centers will enroll up to 1200 subjects to randomize approximately 480 subjects who meet the entry criteria.

For all subjects, trial visits will occur at 0.5, 1, 1.5, 2, 3, 6, 9 and 12 months post-implant (post anticipated implant for medical management). Visits will occur quarterly from 15 to 24 months and semi-annually thereafter.

Subjects are followed in an identical manner regardless of trial arm.

The data will provide evidence of the safety and efficacy of BAROSTIM THERAPY. The accumulated morbidity and mortality data collected will provide evidence of morbidity and mortality benefit. This trial will involve one or more interim analyses to evaluate when sufficient evidence is reached for the final morbidity and mortality analysis.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 1200
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years and older

Eligibility

Inclusion Criteria:

1. Age 21 years or above.

2. Currently NYHA Class II or III heart failure. For NYHA Class II, must have been NYHA Class III at any point in time within 3 calendar months prior to enrollment or at time of screening (enrollment is defined as the date the subject provided written consent).

3. Left ventricular ejection fraction = 35% within 45 days prior to randomization.

4. Heart failure accompanied by either:

• Core lab NT-proBNP = 400 AND <1600 pg/ml within 45 days prior to randomization OR

• Core lab NT-proBNP < 400 pg/ml within 45 days prior to randomization AND a heart failure hospitalization in the past 12 months.

Note: Heart failure hospitalization may include an overnight hospital or hospital-based observation unit stay with a primary diagnosis of heart failure or an emergency room visit with a primary diagnosis of heart failure.

Note: Screening/Baseline core lab NT-proBNP must be collected in an outpatient setting at a time when the subject is thought to be clinically stable.

5. On optimal, stable, Guideline Directed Medical Therapy (GDMT) per country specific guidelines for the treatment of heart-failure throughout screening/baseline evaluation and for at least 4 weeks prior to obtaining any post-consent screening parameters:

• No more than a 100% increase or a 50% decrease of the dosage of any one medication other than a diuretic.

• Medication changes within a drug class are allowed as long as the equivalent dosage is within the limits specified above.

• Unrestricted changes in diuretics are allowed as long as the subject remains on a diuretic.

6. Six-minute hall walk (6MHW) = 150 m AND = 400 m within 45 days prior to randomization.

7. The artery planned for the BAROSTIM implant must meet both of the following criteria:

• At least one carotid bifurcation as identification by a bilateral carotid duplex ultrasound within 6 months prior to randomization that is:

1. Below the level of the mandible AND

2. No ulcerative carotid arterial plaques AND

3. No carotid atherosclerosis producing a 50% or greater reduction in linear diameter in the internal carotid AND

4. No carotid atherosclerosis producing a 50% or greater reduction in linear diameter in the distal common carotid

• No prior surgery, radiation, or endovascular stent placement in the carotid artery or the carotid sinus region.

8. If female and of childbearing potential, must use a medically accepted method of birth control (e.g., barrier method with spermicide, oral contraceptive, or abstinence) and agree to continue use of this method for the duration of the trial. Women of childbearing potential must have a negative pregnancy test within 14 days prior to randomization.

9. Received a standard cardiac work up and is an appropriate candidate for the study and the surgical procedure as determined by a trial cardiologist and a trial surgeon.

10. Subjects implanted with a cardiac rhythm management device that does not utilize an intracardiac lead, or implanted with a neurostimulation device, must be approved by the CVRx Clinical department.

11. Signed a CVRx-approved informed consent form for participation in this trial.

Exclusion Criteria:

If any of the following criteria are met, subjects are not eligible for this trial.

1. Received cardiac resynchronization therapy (CRT) within six months of randomization, or is actively receiving CRT.

2. Currently have a Class I indication for a cardiac resynchronization therapy (CRT) device according to AHA/ACC/ESC guidelines for the treatment of congestive heart failure. ,

3. Known or suspected baroreflex failure or autonomic neuropathy.

4. AHA/ACC Stage D heart failure within 45 days prior to randomization.

5. Body mass index > 40.

6. Serum estimated glomerular filtration rate (eGFR) < 25 mL/min/1.73 m2 within 45 days prior to randomization.

7. Recurring resting heart rate of either < 60 bpm or > 100 bpm via clinic measurements within 45 days prior to randomization. (Note: Heart rate <60 bpm is not applicable to subjects with an implanted device capable of pacing.)

8. Recurring symptomatic hypotension within 45 days prior to randomization.

9. Significant uncontrolled symptomatic bradyarrhythmias or unstable ventricular arrhythmias.

10. Subjects with any surgery that has occurred, or is planned to occur, within 45 days of the BAROSTIM NEO implant procedure. This includes pacemaker or ICD implants or battery replacements.

11. Episode of NYHA class IV heart failure with acute pulmonary edema within 45 days prior to randomization.

12. Any of the following within 3 months of randomization:

• Myocardial infarction

• Unstable angina

• Percutaneous coronary intervention (e.g. CABG or PTCA)

• Cerebral vascular accident or transient ischemic attack

• Sudden cardiac death

13. Solid organ or hematologic transplant, or currently being actively evaluated for an organ transplant.

14. Has received or is receiving LVAD therapy.

15. Has received or is receiving chronic dialysis.

16. Heart failure secondary to a reversible cause, such as cardiac structural valvular disease, acute myocarditis and pericardial constriction.

17. Primary pulmonary hypertension.

18. Infiltrative cardiomyopathy (e.g. cardiac amyloidosis).

19. Severe COPD or severe restrictive lung disease (e.g. requires chronic steroid use or home oxygen use).

20. Active malignancy.

21. Current or planned treatment with intravenous positive inotrope therapy.

22. Life expectancy less than one year.

23. Clinically significant psychological condition that in the physician's opinion would prohibit the subject's ability to meet the protocol requirements.

24. Unable or unwilling to fulfill the protocol medication compliance, testing, and follow-up requirements (e.g. recent drug abuse).

25. Enrolled and active in another (e.g. device, pharmaceutical, or biological) clinical trial unless approved by the CVRx Clinical department.

26. Subjects with known allergies to silicone and titanium.

Related Conditions & MeSH terms

• Heart Failure

Intervention

Device:
• BAROSTIM NEO® System

Drug:
• Medical Management

Locations

Country	Name	City	State
United Kingdom	Belfast Health & Social Care Trust	Belfast	Northern Ireland
United Kingdom	Royal Papworth Hospital NHS Foundation Trust	Cambridge	Cambridgeshire
United Kingdom	Royal Brompton & Harefield NHS Foundation Trust	Harefield	Middlesex
United Kingdom	Liverpool Heart and Chest Hospital	Liverpool	Merseyside
United States	Presbyterian Heart Group	Albuquerque	New Mexico
United States	Atlantic Clinical Research Center - Cardiology	Atlantis	Florida
United States	Texas Cardiac Arrhythmia Research Foundation	Austin	Texas
United States	Central Cardiology Medical Center	Bakersfield	California
United States	St. Alphonsus Medical Center	Boise	Idaho
United States	St. Elizabeth's Medical Center	Brighton	Massachusetts
United States	Deborah Heart and Lung Center	Browns Mills	New Jersey
United States	Heart and Rhythm Solutions, PLLC	Chandler	Arizona
United States	Medical University of South Carolina	Charleston	South Carolina
United States	Chula Vista Cardiac Center	Chula Vista	California
United States	Sharp Chula Vista Medical Center	Chula Vista	California
United States	Sharp Grossmont	Chula Vista	California
United States	The Christ Hospital	Cincinnati	Ohio
United States	Clearwater Cardiovascular Consultants	Clearwater	Florida
United States	Ohio State University	Columbus	Ohio
United States	John Muir Health Clinical Research Center	Concord	California
United States	Cardiovascular Research Institute of Dallas	Dallas	Texas
United States	Detroit Medical Center Cardiovascular Institute	Detroit	Michigan
United States	NorthShore University Health System	Evanston	Illinois
United States	Washington Regional Medical Center	Fayetteville	Arkansas
United States	McLeod Cardiology Associates	Florence	South Carolina
United States	Holy Cross Hospital	Fort Lauderdale	Florida
United States	Herndon Surgery Center	Fresno	California
United States	University of California, San Francisco - Fresno	Fresno	California
United States	Stern Cardiovascular Foundation	Germantown	Tennessee
United States	Glendale Adventist Medical Center	Glendale	California
United States	North Colorado Medical Center	Greeley	Colorado
United States	Cone Health	Greensboro	North Carolina
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Memorial Cardiovascular Institute	Hollywood	Florida
United States	Cardiovascular Institute of the South	Houma	Louisiana
United States	Private Practice Leadership	Houston	Texas
United States	University of Mississippi Medical Center	Jackson	Mississippi
United States	University of Kansas Medical Center Research Institute, Inc.	Kansas City	Kansas
United States	Memorial Health Services	Laguna Hills	California
United States	Healthcare Partners Clinical Research	Las Vegas	Nevada
United States	University Medical Center of Southern Nevada	Las Vegas	Nevada
United States	Baptist Health Lexington	Lexington	Kentucky
United States	University of Kentucky	Lexington	Kentucky
United States	Nebraska Heart Institute	Lincoln	Nebraska
United States	Los Alamitos Cardiovascular	Los Alamitos	California
United States	Southern California Permanente Medical Group	Los Angeles	California
United States	University of Southern California	Los Angeles	California
United States	Medical Center of the Rockies Research	Loveland	Colorado
United States	Mercer University	Macon	Georgia
United States	WellStar Medical Group	Marietta	Georgia
United States	Chan Heart Rhythm Institute	Mesa	Arizona
United States	Columbia St. Mary's Hospital	Milwaukee	Wisconsin
United States	Advanced Cardiovascular Specialists	Mountain View	California
United States	Intermountain Heart Institute	Murray	Utah
United States	Advocate Medical Group	Naperville	Illinois
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Tulane University & Vascular Institute	New Orleans	Louisiana
United States	Hoag Memorial Hospital	Newport Beach	California
United States	Oklahoma Cardiovascular Research Group	Oklahoma City	Oklahoma
United States	UC Irvine Health	Orange	California
United States	AdventHealth Orlando	Orlando	Florida
United States	Desert Heart Regional Medical Center	Palm Springs	California
United States	Huntington Hospital	Pasadena	California
United States	Avanza Medical Research Center	Pensacola	Florida
United States	Drexel University	Philadelphia	Pennsylvania
United States	Arizona Arrhythmia Research Center	Phoenix	Arizona
United States	Cardiovascular Consultants, Ltd.	Phoenix	Arizona
United States	Phoenix Cardiovascular Research Group	Phoenix	Arizona
United States	Allegheny-Singer Research Institute	Pittsburgh	Pennsylvania
United States	Oregon Health & Science University	Portland	Oregon
United States	WakeMed	Raleigh	North Carolina
United States	Methodist Richardson Medical Center	Richardson	Texas
United States	University of Rochester	Rochester	New York
United States	St. Francis Hospital - Long Island	Roslyn	New York
United States	Dignity Health	Sacramento	California
United States	Ascension St. Mary's Research Institute	Saginaw	Michigan
United States	Adventist Heart Institute	Saint Helena	California
United States	Mercy Hospital St. Louis	Saint Louis	Missouri
United States	St. Louis Heart and Vascular	Saint Louis	Missouri
United States	Washington University	Saint Louis	Missouri
United States	University of Utah	Salt Lake City	Utah
United States	University of California San Francisco	San Francisco	California
United States	Bonometti, Inc	Santa Barbara	California
United States	Virginia Mason Medical Center	Seattle	Washington
United States	Providence-Providence Park Hospital	Southfield	Michigan
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Prairie Education and Research Cooperative	Springfield	Illinois
United States	CHI Franciscan Health Research Center	Tacoma	Washington
United States	University of South Florida	Tampa	Florida
United States	Tyler Cardiovascular Consultants	Tyler	Texas
United States	Via Christi Research	Wichita	Kansas
United States	Wake Forest Baptist Health	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
CVRx, Inc.

Countries where clinical trial is conducted

United States,  United Kingdom, 

References & Publications (19)

Abraham WT, Zile MR, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex Activation Therapy for the Treatment of Heart Failure With a Reduced Ejection Fraction. JACC Heart Fail. 2015 Jun;3(6):487-496. doi: 10.1016/j.jchf.2015.02.006. Epub 2015 May 14. — View Citation

Anand IS, Claggett B, Liu J, Shah AM, Rector TS, Shah SJ, Desai AS, O'Meara E, Fleg JL, Pfeffer MA, Pitt B, Solomon SD. Interaction Between Spironolactone and Natriuretic Peptides in Patients With Heart Failure and Preserved Ejection Fraction: From the TOPCAT Trial. JACC Heart Fail. 2017 Apr;5(4):241-252. doi: 10.1016/j.jchf.2016.11.015. — View Citation

Anand IS, Rector TS, Cleland JG, Kuskowski M, McKelvie RS, Persson H, McMurray JJ, Zile MR, Komajda M, Massie BM, Carson PE. Prognostic value of baseline plasma amino-terminal pro-brain natriuretic peptide and its interactions with irbesartan treatment effects in patients with heart failure and preserved ejection fraction: findings from the I-PRESERVE trial. Circ Heart Fail. 2011 Sep;4(5):569-77. doi: 10.1161/CIRCHEARTFAILURE.111.962654. Epub 2011 Jun 29. — View Citation

Cleland JG, McMurray JJ, Kjekshus J, Cornel JH, Dunselman P, Fonseca C, Hjalmarson A, Korewicki J, Lindberg M, Ranjith N, van Veldhuisen DJ, Waagstein F, Wedel H, Wikstrand J; CORONA Study Group. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol. 2009 Nov 10;54(20):1850-9. doi: 10.1016/j.jacc.2009.06.041. — View Citation

Esler M, Kaye D. Increased sympathetic nervous system activity and its therapeutic reduction in arterial hypertension, portal hypertension and heart failure. J Auton Nerv Syst. 1998 Oct 15;72(2-3):210-9. doi: 10.1016/s0165-1838(98)00107-6. — View Citation

Ferreira JP, Duarte K, Graves TL, Zile MR, Abraham WT, Weaver FA, Lindenfeld J, Zannad F. Natriuretic Peptides, 6-Min Walk Test, and Quality-of-Life Questionnaires as Clinically Meaningful Endpoints in HF Trials. J Am Coll Cardiol. 2016 Dec 20;68(24):2690-2707. doi: 10.1016/j.jacc.2016.09.936. — View Citation

Fruhwald FM, Fahrleitner-Pammer A, Berger R, Leyva F, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert JC, Cleland JG. Early and sustained effects of cardiac resynchronization therapy on N-terminal pro-B-type natriuretic peptide in patients with moderate to severe heart failure and cardiac dyssynchrony. Eur Heart J. 2007 Jul;28(13):1592-7. doi: 10.1093/eurheartj/ehl505. Epub 2007 Feb 13. — View Citation

Fu Q, Zhang R, Witkowski S, Arbab-Zadeh A, Prasad A, Okazaki K, Levine BD. Persistent sympathetic activation during chronic antihypertensive therapy: a potential mechanism for long term morbidity? Hypertension. 2005 Apr;45(4):513-21. doi: 10.1161/01.HYP.0000158312.63381.c1. Epub 2005 Feb 28. — View Citation

Georgakopoulos D, Wagner D, Cates AW, Irwin E, Lovett EG. Effects of electrical stimulation of the carotid sinus baroreflex using the Rheos device on ventricular-vascular coupling and myocardial efficiency assessed by pressure-volume relations in non-vagotomized anesthetized dogs. Annu Int Conf IEEE Eng Med Biol Soc. 2009;2009:2025-9. doi: 10.1109/IEMBS.2009.5334421. — View Citation

Gronda E, Francis D, Zannad F, Hamm C, Brugada J, Vanoli E. Baroreflex activation therapy: a new approach to the management of advanced heart failure with reduced ejection fraction. J Cardiovasc Med (Hagerstown). 2017 Sep;18(9):641-649. doi: 10.2459/JCM.0000000000000544. — View Citation

Gronda E, Seravalle G, Brambilla G, Costantino G, Casini A, Alsheraei A, Lovett EG, Mancia G, Grassi G. Chronic baroreflex activation effects on sympathetic nerve traffic, baroreflex function, and cardiac haemodynamics in heart failure: a proof-of-concept study. Eur J Heart Fail. 2014 Sep;16(9):977-83. doi: 10.1002/ejhf.138. Epub 2014 Jul 28. — View Citation

Peters TK, Koralewski HE, Zerbst E. Blood pressure and heart rate changes during physical activity upon heart rate feedback-controlled electrical carotid sinus nerve stimulation. Int J Cardiol. 1989 Mar;22(3):389-92. doi: 10.1016/0167-5273(89)90281-7. — View Citation

Sabbah HN, Gupta RC, Imai M, Irwin ED, Rastogi S, Rossing MA, Kieval RS. Chronic electrical stimulation of the carotid sinus baroreflex improves left ventricular function and promotes reversal of ventricular remodeling in dogs with advanced heart failure. Circ Heart Fail. 2011 Jan;4(1):65-70. doi: 10.1161/CIRCHEARTFAILURE.110.955013. Epub 2010 Nov 19. — View Citation

Sleight P. The importance of the autonomic nervous system in health and disease. Aust N Z J Med. 1997 Aug;27(4):467-73. doi: 10.1111/j.1445-5994.1997.tb02220.x. — View Citation

Weaver FA, Abraham WT, Little WC, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Madershahian N, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Zile MR. Surgical Experience and Long-term Results of Baroreflex Activation Therapy for Heart Failure With Reduced Ejection Fraction. Semin Thorac Cardiovasc Surg. 2016 Summer;28(2):320-328. doi: 10.1053/j.semtcvs.2016.04.017. Epub 2016 Jun 2. — View Citation

Zile MR, Abraham WT, Lindenfeld J, Weaver FA, Zannad F, Graves T, Rogers T, Galle EG. First granted example of novel FDA trial design under Expedited Access Pathway for premarket approval: BeAT-HF. Am Heart J. 2018 Oct;204:139-150. doi: 10.1016/j.ahj.2018.07.011. Epub 2018 Jul 22. — View Citation

Zile MR, Abraham WT, Weaver FA, Butter C, Ducharme A, Halbach M, Klug D, Lovett EG, Muller-Ehmsen J, Schafer JE, Senni M, Swarup V, Wachter R, Little WC. Baroreflex activation therapy for the treatment of heart failure with a reduced ejection fraction: safety and efficacy in patients with and without cardiac resynchronization therapy. Eur J Heart Fail. 2015 Oct;17(10):1066-74. doi: 10.1002/ejhf.299. Epub 2015 Jun 10. — View Citation

Zile MR, Claggett BL, Prescott MF, McMurray JJ, Packer M, Rouleau JL, Swedberg K, Desai AS, Gong J, Shi VC, Solomon SD. Prognostic Implications of Changes in N-Terminal Pro-B-Type Natriuretic Peptide in Patients With Heart Failure. J Am Coll Cardiol. 2016 Dec 6;68(22):2425-2436. doi: 10.1016/j.jacc.2016.09.931. — View Citation

Zucker IH, Hackley JF, Cornish KG, Hiser BA, Anderson NR, Kieval R, Irwin ED, Serdar DJ, Peuler JD, Rossing MA. Chronic baroreceptor activation enhances survival in dogs with pacing-induced heart failure. Hypertension. 2007 Nov;50(5):904-10. doi: 10.1161/HYPERTENSIONAHA.107.095216. Epub 2007 Sep 10. — View Citation

* Note: There are 19 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of Cardiovascular Mortality and Heart Failure Morbidity	To demonstrate that treatment with the BAROSTIM NEO® System, relative to medical management, reduces the rate of cardiovascular mortality or worsening heart failure that leads to hospitalization, cardiac assist device or heart transplant.	At study completion, approximately 5 years
Primary	Major Adverse Neurological and Cardiovascular Events (MANCE)	To demonstrate the safety of the Barostim NEO® System via the event-free rate of all system- and procedure-related Major Adverse Neurological and Cardiovascular Events (MANCE) occurring within 6 months post implant in the device arm.	6 months post implant
Primary	Amino-terminal prohormone of brain natriuretic peptide (NT-proBNP)	To demonstrate that treatment with the BAROSTIM NEO® system results in a larger reduction in NT-proBNP at 6 months than medical management.	6 months post implant
Primary	Six Minute Hall Walk (6MHW)	To demonstrate that treatment with the BAROSTIM NEO® system results in a larger improvement in 6MHW at 6 months than medical management	6 months post implant.
Primary	Minnesota Living With Heart Failure Quality of Life (MLWHF QOL)	To demonstrate that treatment with the BAROSTIM NEO® System results in a larger improvement in MLWHF QOL at 6 months than medical management	6 months post implant

External Links

•   Sponsor Website
•   Study Website