Respicardia, Inc. Pivotal Trial of the remedē System

Not Applicable

Completed

• Conditions: Heart Failure; Sleep Apnea, Central; Sleep Disordered Breathing
• Interventions: Device: Treatment Group (transvenous stimulation of the phrenic nerve); Device: Control Group (Optimal Medical Therapy)

• Registration Number: NCT01816776
• Lead Sponsor: Respicardia, Inc.

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-03
• Study First Submitted: 2013-03-19
• Study First Submitted QC: 2013-03-21
• Study First Posted: 2013-03-22
• Primary Completion: 2016-09-10
• Results First Submitted: 2017-06-13
• Results First Submitted QC: 2017-06-13
• Results First Posted: 2017-07-11
• Study Completion: 2017-11-07
• Status Verified: 2018-05
• Last Update Submitted: 2018-05-31
• Last Update Posted: 2018-06-29

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 151

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Treatment Group	Treatment Group (transvenous stimulation of the phrenic nerve)	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).
Control group	Control Group (Optimal Medical Therapy)	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).

Primary Outcome Measures

Name	Time	Method
Freedom From Related Serious Adverse Events Within 12 Months	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.
The Proportion of Participants Experiencing a Reduction in Apnea-hypopnea Index (AHI)	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Rapid Eye Movement (REM) Sleep Change From Baseline at 6 Months	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.
Central Apnea Index (CAI) Change From Baseline at 6 Months	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.
Apnea-Hypopnea Index (AHI) Change From Baseline at 6 Months	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.
The Proportion of Participants Experiencing a Marked or Moderate Improvement in Patient Global Assessment at 6 Months	6 months	The proportion of subjects with a "moderate" or "marked" improvement in the Patient Global Assessment from baseline to the 6 month visit
Oxygen Desaturation Index 4% (ODI4) Change From Baseline at 6 Months	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%.
Arousal Index (ArI) Change From Baseline at 6 Months	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.
Epworth Sleepiness Scale (ESS) Change From Baseline at 6 Months	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.

Trial Locations

Locations (30)

Detroit Clinical Research Center; 🇺🇸 Farmington Hills, Michigan, United States

Virginia Commonwealth University; 🇺🇸 Richmond, Virginia, United States

Lancaster General Hospital; 🇺🇸 Lancaster, Pennsylvania, United States

University of Maryland, Baltimore; 🇺🇸 Baltimore, Maryland, United States

Charite Medical School, Campus Virchow-Klinikum; 🇩🇪 Berlin, Germany

Keck Hospital of USC; 🇺🇸 Los Angeles, California, United States

Advocate Medical Group; 🇺🇸 Downers Grove, Illinois, United States

University of Florida - Jacksonville; 🇺🇸 Jacksonville, Florida, United States

Johns Hopkins Bayview Medical Center; 🇺🇸 Baltimore, Maryland, United States

Edward Hospital-Advocate Medical Group; 🇺🇸 Naperville, Illinois, United States

United Heart and Vascular (Allina); 🇺🇸 Saint Paul, Minnesota, United States

Spectrum Health; 🇺🇸 Grand Rapids, Michigan, United States

Mid America Heart Institute; 🇺🇸 Kansas City, Missouri, United States

Cooper Health System; 🇺🇸 Cherry Hill, New Jersey, United States

Bryan Heart; 🇺🇸 Lincoln, Nebraska, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Hospital of University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States

Novant Medical Group, Inc. Presbyterian Sleep Health Charlotte; 🇺🇸 Charlotte, North Carolina, United States

The Lindner Center for Research and Education at Christ Hospital; 🇺🇸 Cincinnati, Ohio, United States

Stern Cardiovascular; 🇺🇸 Memphis, Tennessee, United States

Forsyth Medical Center - Novant; 🇺🇸 Winston-Salem, North Carolina, United States

Ohio State University; 🇺🇸 Columbus, Ohio, United States

Bernau-Herzzentruym Brandenburg; 🇩🇪 Bernau, Germany

Fourth Military Hospital; 🇵🇱 Wroclaw, Poland

Marshfield Clinic; 🇺🇸 Marshfield, Wisconsin, United States

Methodist Healthcare System; 🇺🇸 San Antonio, Texas, United States

Bad Oeynhausen- Heart & Diabetes Center; 🇩🇪 Bad Oeynhausen, Germany

Hamburg: Universitares Herzzentrum; 🇩🇪 Hamburg, Germany

Bielefeld-Klinikun; 🇩🇪 Bielefeld, Germany

Ambulantes Herzzentrum-Kassel; 🇩🇪 Kassel, Germany