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Sleep Apnea, CentralNCT01816776

Respicardia, Inc. Pivotal Trial of the remedē System

A study testing Treatment Group (transvenous stimulation of the phrenic nerve) in people with Sleep Apnea, Central and Sleep Disordered Breathing, run by Respicardia, Inc. at 30 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Treatment Group (transvenous stimulation of the phrenic nerve)
Type of treatment
Medical device
Could I receive a placebo?
No, everyone receives an active treatment
How many people
151 participants
Where
30 sitesin 3 countries
Study dates
Mar 2013to 7 Nov 2017
Phase
Interventional
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.)

Who cannot join

  • 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
Show all 24Show fewer
  • 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
  • In subjects with heart failure, American College of Cardiology (ACC)/American Heart Association Heart (AHA) Stage D
  • 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
  • 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
  • Other anticipated surgery or invasive procedure expected to affect ability to perform testing at 6-month post-therapy initiation visit
  • Unstable angina
  • Allergy to or intolerant of contrast dye
  • Pregnancy or of child bearing potential without a negative pregnancy test within 10 days prior to remede system implant
  • Life expectancy or expected time to transplant or left ventricular assist device of less than 12 months
  • Currently enrolled or planning to enroll in another study that may conflict with protocol requirements or confound subject results in this trial

Trial locations and contacts

30 sites in 3 countries.

30 sites in 3 countries

United States23 sites

  • University of Maryland, Baltimore

    Baltimore, Maryland, 21201

  • Johns Hopkins Bayview Medical Center

    Baltimore, Maryland, 21287

  • Novant Medical Group, Inc. Presbyterian Sleep Health Charlotte

    Charlotte, North Carolina, 28204

  • Cooper Health System

    Cherry Hill, New Jersey, 08034

  • The Lindner Center for Research and Education at Christ Hospital

    Cincinnati, Ohio, 45219

  • Ohio State University

    Columbus, Ohio, 43210

  • Advocate Medical Group

    Downers Grove, Illinois, 60566

  • Detroit Clinical Research Center

    Farmington Hills, Michigan, 48334

  • Spectrum Health

    Grand Rapids, Michigan, 49525

  • University of Florida - Jacksonville

    Jacksonville, Florida, 32209

  • Mid America Heart Institute

    Kansas City, Missouri, 64111

  • Lancaster General Hospital

    Lancaster, Pennsylvania, 17603

  • Bryan Heart

    Lincoln, Nebraska, 68506

  • Keck Hospital of USC

    Los Angeles, California, 90033

  • Marshfield Clinic

    Marshfield, Wisconsin, 54449

  • Stern Cardiovascular

    Memphis, Tennessee, 38138

  • Edward Hospital-Advocate Medical Group

    Naperville, Illinois, 60566

  • Hospital of University of Pennsylvania

    Philadelphia, Pennsylvania, 19104

  • Virginia Commonwealth University

    Richmond, Virginia, 23219

  • United Heart and Vascular (Allina)

    Saint Paul, Minnesota, 55102

  • Methodist Healthcare System

    San Antonio, Texas, 78229

  • Washington University

    St Louis, Missouri, 63110

  • Forsyth Medical Center - Novant

    Winston-Salem, North Carolina, 27103

Other trials in United States

Germany6 sites

  • Bad Oeynhausen- Heart & Diabetes Center

    Bad Oeynhausen

  • Charite Medical School, Campus Virchow-Klinikum

    Berlin

  • Bernau-Herzzentruym Brandenburg

    Bernau

  • Bielefeld-Klinikun

    Bielefeld

  • Hamburg: Universitares Herzzentrum

    Hamburg

  • Ambulantes Herzzentrum-Kassel

    Kassel

Other trials in Germany

Poland1 site

  • Fourth Military Hospital

    Wroclaw

Other trials in Poland

About this study

Official title: A Randomized Trial Evaluating the Safety and Effectiveness of the remedē® System in Patients With Central Sleep Apnea

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.

Being tested
Treatment Group (transvenous stimulation of the phrenic nerve), Control Group (Optimal Medical Therapy)
Medical subject headings
Sleep Apnea, Central, Sleep Apnea Syndromes, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

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

    Also called remedē System, Transvenous stimulation of the phrenic nerve

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

  • Control Group (Optimal Medical Therapy)Device

    Also called Optimal Medical Therapy

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

Study groups in NCT01816776
Study groupRoleWhat they receive
Treatment GroupExperimentalSubjects 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).
Receives: Device: Treatment Group (transvenous stimulation of the phrenic nerve)
Control groupOtherSubjects 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).
Receives: Device: Control Group (Optimal Medical Therapy)

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 6 months

  2. 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.

    Measured: 12 months

Secondary outcomes (7)

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

    Change in CAI = Month 6 index - Baseline index. The central apnea index is a measurement used to indicate the severity of central sleep apnea. It is represented by the number of central apnea events per hour of sleep.

    Measured: 6 months

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

    Change in AHI = Month 6 index - Baseline index. The Apnea-Hypopnea Index is a measurement used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep.

    Measured: 6 months

  3. Arousal Index (ArI) Change From Baseline at 6 Months

    Change in ArI = Month 6 index - Baseline index. The Arousal Index is a measurement used to indicate the number of times per hour of sleep that sleep is disrupted.

    Measured: 6 months

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

    Change in REM = Month 6 percentage - Baseline percentage. Rapid Eye Movement (REM) is a sleep stage. A higher percentage of sleep in REM is a measure of better sleep quality.

    Measured: 6 months

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

    The proportion of subjects with a "moderate" or "marked" improvement in the Patient Global Assessment from baseline to the 6 month visit

    Measured: 6 months

  6. Oxygen Desaturation Index 4% (ODI4) Change From Baseline at 6 Months

    Change in ODI4 = Month 6 index - Baseline index. The Oxygen Desaturation Index 4% is a measurement of the number of times per hour of sleep that the blood's oxygen level drops ≥4%.

    Measured: 6 months

  7. Epworth Sleepiness Scale (ESS) Change From Baseline at 6 Months

    Change in ESS = Month 6 score - Baseline score. The ESS is an assessment to measure a subject's general level of daytime sleepiness. Scores can range from 0-24, with higher scores indicating higher level of daytime sleepiness.

    Measured: 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Mar 2013 (estimated)
  2. Study startMar 2013
  3. Primary completion10 Sep 2016
  4. Study completion7 Nov 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
151 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01816776
Sponsor's protocol ID
Respicardia CR-1005
Status last verified
May 2018
First submitted
19 Mar 2013
Last updated
29 Jun 2018
Data monitoring committee
Yes

Publications

  • Khayat R, Khan M, Morgenthaler TI, McKane S, Germany R, Costanzo MR. Automatic activation of neurostimulation for central sleep apnea results in high nightly usage. J Clin Sleep Med. 2026 Feb 27;22(1):39. doi: 10.1007/s44470-026-00051-5.

    PubMed 41761012

  • Javaheri S, McKane SW, Germany RE. Changes in quality of life in patients with atrial fibrillation and central sleep apnea treated with transvenous phrenic nerve stimulation. Sleep Med. 2026 May;141:108824. doi: 10.1016/j.sleep.2026.108824. Epub 2026 Feb 2.

    PubMed 41643229

  • 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.

    PubMed 41025409

  • 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.

    PubMed 37436669

  • 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.

    PubMed 37284759

  • 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.

    PubMed 33953626

  • 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.

    PubMed 33745107

  • 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.

    PubMed 32946372

  • 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.

    PubMed 32803641

  • 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.

    PubMed 32789619

  • 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.

    PubMed 31634407

  • 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.

    PubMed 27598679

  • 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.

    PubMed 26432647

Questions about this trial

What is this clinical trial studying?

A study testing Treatment Group (transvenous stimulation of the phrenic nerve) in people with Sleep Apnea, Central and Sleep Disordered Breathing, run by Respicardia, Inc. at 30 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 29 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 30 sites in United States, Germany, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 11 Jul 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

The Proportion of Participants Experiencing a Reduction in Apnea-hypopnea Index (AHI) (time frame: 6 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01816776, which also lists 13 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Jun 2018.

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