Respicardia, Inc. Pivotal Trial of the remedē System

Heart Failure Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01816776
• Other study ID #: Respicardia CR-1005
• Status: Completed
• Phase: N/A
• Start date: March 2013
• Est. completion date: November 7, 2017

Study information

• Verified date: May 2018
• Source: Respicardia, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical 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 medical management and implanted but inactive remedē® systems.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 151
• Est. completion date: November 7, 2017
• Est. primary completion date: September 10, 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Heart Failure
• Sleep Apnea Syndromes
• Sleep Apnea, Central
• Sleep Disordered Breathing

Intervention

Device:
• Treatment Group (transvenous stimulation of the phrenic nerve)
device implant, optimal medical therapy and device initiation 1 month post implant.
• Control Group (Optimal Medical Therapy)
device implant, optimal medical therapy and delayed device initiation (7 months post device implant)

Locations

Country	Name	City	State
Germany	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
Poland	Fourth Military Hospital	Wroclaw
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	University of Maryland, Baltimore	Baltimore	Maryland
United States	Novant Medical Group, Inc. Presbyterian Sleep Health Charlotte	Charlotte	North Carolina
United States	Cooper Health System	Cherry Hill	New Jersey
United States	The Lindner Center for Research and Education at Christ Hospital	Cincinnati	Ohio
United States	Ohio State University	Columbus	Ohio
United States	Advocate Medical Group	Downers Grove	Illinois
United States	Detroit Clinical Research Center	Farmington Hills	Michigan
United States	Spectrum Health	Grand Rapids	Michigan
United States	University of Florida - Jacksonville	Jacksonville	Florida
United States	Mid America Heart Institute	Kansas City	Missouri
United States	Lancaster General Hospital	Lancaster	Pennsylvania
United States	Bryan Heart	Lincoln	Nebraska
United States	Keck Hospital of USC	Los Angeles	California
United States	Marshfield Clinic	Marshfield	Wisconsin
United States	Stern Cardiovascular	Memphis	Tennessee
United States	Edward Hospital-Advocate Medical Group	Naperville	Illinois
United States	Hospital of University of Pennsylvania	Philadelphia	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	United Heart and Vascular (Allina)	Saint Paul	Minnesota
United States	Methodist Healthcare System	San Antonio	Texas
United States	Forsyth Medical Center - Novant	Winston-Salem	North Carolina

Sponsors (1)

Lead Sponsor	Collaborator
Respicardia, Inc.

Countries where clinical trial is conducted

United States,  Germany,  Poland, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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.	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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.	6 months
Secondary	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	6 months
Secondary	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%.	6 months
Secondary	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.	6 months