Respicardia, Inc. Pivotal Trial of the remedē System

NCT01816776 | Completed Results DMC

• 1 other identifier: Respicardia CR-1005
• Study Type: interventional
• Target: 151
• Locations: 3 countries
• Sites: 30

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

Outcome Measures

Primary Outcomes (2)

• The Proportion of Participants Experiencing a Reduction in Apnea-hypopnea Index (AHI)

  Comparison of the proportion of subjects in the Treatment group achieving a 50% or greater reduction in AHI from baseline to 6 months compared to the Control group.

  6 months

• Freedom From Related Serious Adverse Events Within 12 Months

  Freedom from serious adverse events (SAEs) associated with the implant procedure, the remede System, or the delivered therapy at 12 months post therapy initiation visit.

  12 months

Secondary Outcomes (7)

• Central Apnea Index (CAI) Change From Baseline at 6 Months

  6 months

• Apnea-Hypopnea Index (AHI) Change From Baseline at 6 Months

  6 months

• Arousal Index (ArI) Change From Baseline at 6 Months

  6 months

• Rapid Eye Movement (REM) Sleep Change From Baseline at 6 Months

  6 months

• The Proportion of Participants Experiencing a Marked or Moderate Improvement in Patient Global Assessment at 6 Months

  6 months

Study Arms (2)

Treatment Group

EXPERIMENTAL

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).

Device: Treatment Group (transvenous stimulation of the phrenic nerve)

Control group

OTHER

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).

Device: Control Group (Optimal Medical Therapy)

Interventions

Treatment Group (transvenous stimulation of the phrenic nerve) DEVICE

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

Also known as: remedē System, Transvenous stimulation of the phrenic nerve

Treatment Group

Control Group (Optimal Medical Therapy) DEVICE

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

Also known as: Optimal Medical Therapy

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• At least 18 years of age
• 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
• 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
• 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.
• In the investigator's opinion, willing and able to comply with all study requirements
• Signed the Institutional Review Board/Medical Ethics Committee approved informed consent (HIPAA authorization in the U.S.)

You may not qualify if:

• Pacemaker dependent subjects without any physiologic escape rhythm
• Suspected inability to place catheter for delivery of stimulation lead (e.g. previously know coagulopathy, distorted anatomy, prior failed pectoral implant, etc.)
• Evidence of phrenic nerve palsy
• More than 2 previous open chest surgical procedures (e.g., CABG)
• Etiology of central sleep apnea known to be caused primarily by pain medication
• Documented history of psychosis or severe bipolar disorder
• Cerebrovascular accident (CVA) within 12 months of baseline testing
• History of idiopathic pulmonary hypertension, World Health Organization Class 1
• 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
• Baseline oxygen saturation less than 92% while awake and on room air after 5 minutes of quiet rest
• Anticipated need for chronic oxygen therapy or breathing mask-based therapy for 6 months post therapy initiation visit
• Active infection or sepsis within 30 days of enrollment
• 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
• 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)
• Hemoglobin less than 8 gm/dL

Sponsors & Collaborators

• Respicardia, Inc.: lead

Study Sites (30)

Keck Hospital of USC

Los Angeles, California, 90033, United States

Location

University of Florida - Jacksonville

Jacksonville, Florida, 32209, United States

Location

Advocate Medical Group

Downers Grove, Illinois, 60566, United States

Location

Edward Hospital-Advocate Medical Group

Naperville, Illinois, 60566, United States

Location

University of Maryland, Baltimore

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21287, United States

Location

Detroit Clinical Research Center

Farmington Hills, Michigan, 48334, United States

Location

Spectrum Health

Grand Rapids, Michigan, 49525, United States

Location

United Heart and Vascular (Allina)

Saint Paul, Minnesota, 55102, United States

Location

Mid America Heart Institute

Kansas City, Missouri, 64111, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Bryan Heart

Lincoln, Nebraska, 68506, United States

Location

Cooper Health System

Cherry Hill, New Jersey, 08034, United States

Location

Novant Medical Group, Inc. Presbyterian Sleep Health Charlotte

Charlotte, North Carolina, 28204, United States

Location

Forsyth Medical Center - Novant

Winston-Salem, North Carolina, 27103, United States

Location

The Lindner Center for Research and Education at Christ Hospital

Cincinnati, Ohio, 45219, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Lancaster General Hospital

Lancaster, Pennsylvania, 17603, United States

Location

Hospital of University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Stern Cardiovascular

Memphis, Tennessee, 38138, United States

Location

Methodist Healthcare System

San Antonio, Texas, 78229, United States

Location

Virginia Commonwealth University

Richmond, Virginia, 23219, United States

Location

Marshfield Clinic

Marshfield, Wisconsin, 54449, United States

Location

Bad Oeynhausen- Heart & Diabetes Center

Bad Oeynhausen, Germany

Location

Charite Medical School, Campus Virchow-Klinikum

Berlin, Germany

Location

Bernau-Herzzentruym Brandenburg

Bernau, Germany

Location

Bielefeld-Klinikun

Bielefeld, Germany

Location

Hamburg: Universitares Herzzentrum

Hamburg, Germany

Location

Ambulantes Herzzentrum-Kassel

Kassel, Germany

Location

Fourth Military Hospital

Wroclaw, Poland

Location

Related Publications (11)

• 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 Dec 1;21(12):2113-2120. doi: 10.5664/jcsm.11904.

  PMID: 41025409 DERIVED

• 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.

  PMID: 37436669 DERIVED

• 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.

  PMID: 37284759 DERIVED

• 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.

  PMID: 33953626 DERIVED

• 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.

  PMID: 33745107 DERIVED

• 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.

  PMID: 32946372 DERIVED

• 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.

  PMID: 32803641 DERIVED

• 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.

  PMID: 32789619 DERIVED

• 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.

  PMID: 31634407 DERIVED

• 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.

  PMID: 27598679 DERIVED

• 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.

  PMID: 26432647 DERIVED

MeSH Terms

Conditions

Sleep Apnea, Central; Sleep Apnea Syndromes; Heart Failure

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Results Point of Contact

• Title: Linda Nelson, VP Clinical Affairs
• Organization: Respicardia, Inc.

lnelson@respicardia.com

952-540-4479

Study Officials

• Maria Rosa Costanzo, M.D.

  Midwest Heart Specialists

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 19, 2013
• First Posted: March 22, 2013
• Study Start: March 1, 2013
• Primary Completion: September 10, 2016
• Study Completion: November 7, 2017
• Last Updated: June 29, 2018
• Results First Posted: July 11, 2017

Record last verified: 2018-05

Locations

US (23); PL (1); DE (6)