Respicardia, Inc. Pivotal Trial of the remedē System

NCT ID: NCT01816776

Last Updated: 2018-06-29

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 151 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-03-31
• Study Completion Date: 2017-11-07

Brief Summary

The primary purpose of this prospective, multicenter, randomized trial is to evaluate the safety and effectiveness of therapy delivered by the remedē® system in subjects with moderate to severe central sleep apnea and optimal medical management, compared to outcomes in randomized control subjects receiving optimal medical management and implanted but inactive remedē® systems.

Conditions

Sleep Apnea, Central; Sleep Disordered Breathing; Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Treatment Group

Subjects implanted with the remedē system device and randomized to the Treatment group will receive optimal medical therapy and have the remedē system initiated to deliver transvenous stimulation of the phrenic nerve at the Therapy Initiation Visit (1 month post device implant).

Group Type: EXPERIMENTAL

Treatment Group (transvenous stimulation of the phrenic nerve)

Intervention Type: DEVICE

device implant, optimal medical therapy and device initiation 1 month post implant.

Control group

Subjects implanted with the remedē system device and randomized to the Control group will receive optimal medical therapy through the 6-month Post-Therapy Initiation Visit. Control group subjects will have the remedē system initiated to deliver transvenous stimulation of the phrenic nerve at the 6-month Post-Therapy Initiation Visit (7 months post device implant).

Group Type: OTHER

Control Group (Optimal Medical Therapy)

Intervention Type: DEVICE

device implant, optimal medical therapy and delayed device initiation (7 months post device implant)

Interventions

Treatment Group (transvenous stimulation of the phrenic nerve)

device implant, optimal medical therapy and device initiation 1 month post implant.

Intervention Type: DEVICE

Control Group (Optimal Medical Therapy)

device implant, optimal medical therapy and delayed device initiation (7 months post device implant)

Intervention Type: DEVICE

Other Intervention Names

remedē System; Transvenous stimulation of the phrenic nerve; Optimal Medical Therapy

Eligibility Criteria

Inclusion Criteria

1. At least 18 years of age

2. Central Sleep apnea confirmed by core lab analysis of PSG with EEG within 40 days of scheduled implant:

• Apnea/Hypopnea Index (AHI) greater than or equal to 20;
• Central Apnea Index (CAI) at least 50% of all apneas, with at least 30 central apnea events;
• Oxygen Desaturation Index (OAI) less than or equal to 20% of the total AHI

3. Medically stable for 30 days prior to all baseline testing (including PSG), i.e., no hospitalizations for illness, no breathing mask-based therapy, and on stable medications and therapies:

• Stable medications are defined as no changes during this period except for those within a pre-specified sliding scale medication regimen;
• If the subject has heart failure, the baseline testing (including PSG) should occur at least 6 months after initial diagnosis;
• If the subject has systolic heart failure, the baseline testing (including PSG) should occur after maximally titrating beta blockers, angiotensin converting enzyme inhibitors (ACE-I) and other medications indicated in the current guidelines (unless contraindicated or not considered medically necessary) and after receiving any indicated device therapy including devices for cardiac resynchronization therapy and/or primary prevention of sudden cardiac death;
• If subject has a hospitalization or physician visit requiring IV medication between the screening PSG and implant, the subject must be re-screened when stable

4. Expected to tolerate study procedures in the opinion of the investigator, in particular:

• Ability to lie down long enough to insert the remede system without shortness of breath and able to tolerate instrumentation for the Polysomnogram/Polygram testing;
• Expected to tolerate therapy titration and the sensation of therapy, and communicate therapy experience.

5. In the investigator's opinion, willing and able to comply with all study requirements

6. Signed the Institutional Review Board/Medical Ethics Committee approved informed consent (HIPAA authorization in the U.S.)

Exclusion Criteria

1. Pacemaker dependent subjects without any physiologic escape rhythm

2. Suspected inability to place catheter for delivery of stimulation lead (e.g. previously know coagulopathy, distorted anatomy, prior failed pectoral implant, etc.)

3. Evidence of phrenic nerve palsy

4. More than 2 previous open chest surgical procedures (e.g., CABG)

5. Etiology of central sleep apnea known to be caused primarily by pain medication

6. Documented history of psychosis or severe bipolar disorder

7. Cerebrovascular accident (CVA) within 12 months of baseline testing

8. History of idiopathic pulmonary hypertension, World Health Organization Class 1

9. Limited pulmonary function with either forced expiratory volume (FEV) 1/forced vital capacity (FVC) less than 65% of predicted value or FVC less than 60% of predicted value

10. Baseline oxygen saturation less than 92% while awake and on room air after 5 minutes of quiet rest

11. Anticipated need for chronic oxygen therapy or breathing mask-based therapy for 6 months post therapy initiation visit

12. Active infection or sepsis within 30 days of enrollment

13. Currently on renal dialysis or creatinine level greater than 2.5 mg/dL or calculated creatinine clearance equal to or less than 30 ml/min using the Cockcroft-Gault equation

14. Poor liver function with baseline aspartate transaminase (AST), alanine transaminase (ALT), and/or total bilirubin greater than 3 times the upper limit of normal (per lab normals at each site)

15. Hemoglobin less than 8 gm/dL

16. In subjects with heart failure, American College of Cardiology (ACC)/American Heart Association Heart (AHA) Stage D

17. Within the 3 months prior to baseline testing, any of the following: uncorrected severe valvular stenosis, valve replacement or repair (percutaneous or surgical), myocardial infarction (MI), coronary artery bypass grafting (CABG) surgery, percutaneous coronary intervention (PCI), cardiac ablation, new cardiac resynchronization device or new pacemaker implant

18. New implantable cardioverter defibrillator or any implantable device generator change-out within 30 days prior to baseline testing or anticipated within the first 6 months of enrollment

19. Other anticipated surgery or invasive procedure expected to affect ability to perform testing at 6-month post-therapy initiation visit

20. Unstable angina

21. Allergy to or intolerant of contrast dye

22. Pregnancy or of child bearing potential without a negative pregnancy test within 10 days prior to remede system implant

23. Life expectancy or expected time to transplant or left ventricular assist device of less than 12 months

24. Currently enrolled or planning to enroll in another study that may conflict with protocol requirements or confound subject results in this trial

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Respicardia, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Maria Rosa Costanzo, M.D.

Role: PRINCIPAL_INVESTIGATOR

Midwest Heart Specialists

Locations

Keck Hospital of USC

Los Angeles, California, United States

University of Florida - Jacksonville

Jacksonville, Florida, United States

Advocate Medical Group

Downers Grove, Illinois, United States

Edward Hospital-Advocate Medical Group

Naperville, Illinois, United States

University of Maryland, Baltimore

Baltimore, Maryland, United States

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, United States

Detroit Clinical Research Center

Farmington Hills, Michigan, United States

Spectrum Health

Grand Rapids, Michigan, United States

United Heart and Vascular (Allina)

Saint Paul, Minnesota, United States

Mid America Heart Institute

Kansas City, Missouri, United States

Washington University

St Louis, Missouri, United States

Bryan Heart

Lincoln, Nebraska, United States

Cooper Health System

Cherry Hill, New Jersey, United States

Novant Medical Group, Inc. Presbyterian Sleep Health Charlotte

Charlotte, North Carolina, United States

Forsyth Medical Center - Novant

Winston-Salem, North Carolina, United States

The Lindner Center for Research and Education at Christ Hospital

Cincinnati, Ohio, United States

Ohio State University

Columbus, Ohio, United States

Lancaster General Hospital

Lancaster, Pennsylvania, United States

Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, United States

Stern Cardiovascular

Memphis, Tennessee, United States

Methodist Healthcare System

San Antonio, Texas, United States

Virginia Commonwealth University

Richmond, Virginia, United States

Marshfield Clinic

Marshfield, Wisconsin, United States

Bad Oeynhausen- Heart & Diabetes Center

Bad Oeynhausen, , Germany

Charite Medical School, Campus Virchow-Klinikum

Berlin, , Germany

Bernau-Herzzentruym Brandenburg

Bernau, , Germany

Bielefeld-Klinikun

Bielefeld, , Germany

Hamburg: Universitares Herzzentrum

Hamburg, , Germany

Ambulantes Herzzentrum-Kassel

Kassel, , Germany

Fourth Military Hospital

Wroclaw, , Poland

Countries

United States; Germany; Poland

References

Costanzo MR, Ponikowski P, Javaheri S, Augostini R, Goldberg L, Holcomb R, Kao A, Khayat RN, Oldenburg O, Stellbrink C, Abraham WT; remede System Pivotal Trial Study Group. Transvenous neurostimulation for central sleep apnoea: a randomised controlled trial. Lancet. 2016 Sep 3;388(10048):974-82. doi: 10.1016/S0140-6736(16)30961-8. Epub 2016 Sep 1.

Reference Type: DERIVED

PMID: 27598679 (View on PubMed)

Costanzo MR, Augostini R, Goldberg LR, Ponikowski P, Stellbrink C, Javaheri S. Design of the remede System Pivotal Trial: A Prospective, Randomized Study in the Use of Respiratory Rhythm Management to Treat Central Sleep Apnea. J Card Fail. 2015 Nov;21(11):892-902. doi: 10.1016/j.cardfail.2015.08.344.

Reference Type: DERIVED

PMID: 26432647 (View on PubMed)

Dupuy-McCauley K, Schwartz AR, Javaheri S, Germany R, McKane S, Morgenthaler TI. Classifying hypopneas as obstructive or central can enhance transvenous phrenic nerve stimulation therapy patient selection and outcomes. J Clin Sleep Med. 2025 Sep 30. doi: 10.5664/jcsm.11904. Online ahead of print.

Reference Type: DERIVED

PMID: 41025409 (View on PubMed)

Samii S, McKane S, Meyer TE, Shah N. Analysis by sex of safety and effectiveness of transvenous phrenic nerve stimulation. Sleep Breath. 2024 Mar;28(1):165-171. doi: 10.1007/s11325-023-02882-5. Epub 2023 Jul 12.

Reference Type: DERIVED

PMID: 37436669 (View on PubMed)

Baumert M, Linz D, McKane S, Immanuel S. Transvenous phrenic nerve stimulation is associated with normalization of nocturnal heart rate perturbations in patients with central sleep apnea. Sleep. 2023 Sep 8;46(9):zsad166. doi: 10.1093/sleep/zsad166.

Reference Type: DERIVED

PMID: 37284759 (View on PubMed)

Costanzo MR, Javaheri S, Ponikowski P, Oldenburg O, Augostini R, Goldberg LR, Stellbrink C, Fox H, Schwartz AR, Gupta S, McKane S, Meyer TE, Abraham WT; remede(R)System Pivotal Trial Study Group. Transvenous Phrenic Nerve Stimulation for Treatment of Central Sleep Apnea: Five-Year Safety and Efficacy Outcomes. Nat Sci Sleep. 2021 Apr 29;13:515-526. doi: 10.2147/NSS.S300713. eCollection 2021.

Reference Type: DERIVED

PMID: 33953626 (View on PubMed)

Schwartz AR, Goldberg LR, McKane S, Morgenthaler TI. Transvenous phrenic nerve stimulation improves central sleep apnea, sleep quality, and quality of life regardless of prior positive airway pressure treatment. Sleep Breath. 2021 Dec;25(4):2053-2063. doi: 10.1007/s11325-021-02335-x. Epub 2021 Mar 20.

Reference Type: DERIVED

PMID: 33745107 (View on PubMed)

Javaheri S, McKane S. Transvenous phrenic nerve stimulation to treat idiopathic central sleep apnea. J Clin Sleep Med. 2020 Dec 15;16(12):2099-2107. doi: 10.5664/jcsm.8802.

Reference Type: DERIVED

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Costanzo MR. Central Sleep Apnea in Patients with Heart Failure-How to Screen, How to Treat. Curr Heart Fail Rep. 2020 Oct;17(5):277-287. doi: 10.1007/s11897-020-00472-0.

Reference Type: DERIVED

PMID: 32803641 (View on PubMed)

Oldenburg O, Costanzo MR, Germany R, McKane S, Meyer TE, Fox H. Improving Nocturnal Hypoxemic Burden with Transvenous Phrenic Nerve Stimulation for the Treatment of Central Sleep Apnea. J Cardiovasc Transl Res. 2021 Apr;14(2):377-385. doi: 10.1007/s12265-020-10061-0. Epub 2020 Aug 12.

Reference Type: DERIVED

PMID: 32789619 (View on PubMed)

Fox H, Oldenburg O, Javaheri S, Ponikowski P, Augostini R, Goldberg LR, Stellbrink C, Mckane S, Meyer TE, Abraham WT, Costanzo MR. Long-term efficacy and safety of phrenic nerve stimulation for the treatment of central sleep apnea. Sleep. 2019 Oct 21;42(11):zsz158. doi: 10.1093/sleep/zsz158.

Reference Type: DERIVED

PMID: 31634407 (View on PubMed)

Other Identifiers

Respicardia CR-1005

Identifier Type: -

Identifier Source: org_study_id