Chronic Evaluation of Respicardia Therapy

Study Overview
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Brief Summary
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The purpose of this study is to determine the chronic safety and efficacy of phrenic nerve stimulation on central sleep apnea (CSA). Clinically, CSA events translate into sleep fragmentation, excessive daytime sleepiness, reduced exercise capacity, and possibly ventricular arrhythmias. The study is chronic in nature, such that subjects will undergo the implantation of an implantable pulse generator and stimulation lead. A sensing lead may also be placed during the initial implant procedure. Subjects will be followed for up to six-months on therapy to assess respiratory and heart failure outcomes. Following the six-month therapy visit, subjects will enter into a long-term follow-up phase until the completion of the study. It is anticipated that data obtained in this study will show that the proposed intervention can modify respiration with a low incidence of adverse effects. The results of this trial are intended to be used to develop a subsequent protocol for pivotal study.

Official Title
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Safety and Efficacy Evaluation of Respicardia Therapy for Central Sleep Apnea

Conditions
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Sleep Disordered Breathing, Cheyne Stokes Respiration, Periodic Breathing, Sleep Apnea, Central Sleep Apnea

Intervention / Treatment
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* Device: remedē (TM) system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Candidate is at least 18 years old Candidates with known recent history of Periodic Breathing, as evidenced by an overnight polysomnogram (PSG) within 60 days of the implant procedure demonstrating: Apnea-Hypopnea Index (AHI) greater than or equal to 20 events/hr Predominantly central origin (central apnea events comprise 50% or more of all apnea events) Limited obstructive events (obstructive apneas comprise less than 20% of the AHI) Exclusion Criteria: Candidates who are pregnant Candidates with baseline oxygen saturation less than or equal to 90% on a stable FiO2 Candidates with severe COPD Candidates with a history of cerebrovascular accident (CVA), myocardial infarction, coronary artery bypass grafting (CABG) surgery, or percutaneous coronary intervention (PCI) within the 3 months prior to the study Candidates with unstable angina Candidates with history of primary pulmonary hypertension

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment<br>All enrolled subjects will undergo attempted system implantation and therapeutic assessment. Subjects' baseline assessment values will serve as control parameters for the therapy evaluation. | Device: remedē (TM) system<br>* Implantation of the remedē (TM) system, including implantable pulse generator, stimulation lead, and (optional) sensing lead. Nightly provision of unilateral transvenous phrenic nerve therapy during sleep periods.<br>* Other names: (note: Respicardia was formerly Cardiac Concepts);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AHI Change From Baseline at 3 Months | Change = Month 3 score - Baseline score The Apnea-Hypopnea Index (AHI) is an index used to indicate the severity of sleep apnea. It is represented by the number of apnea and hypopnea events per hour of sleep. | Baseline and 3 months on therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Related Adverse Events | The number of subjects with a serious adverse event (SAE) considered related to the remedē system or implant procedure is provided. The number of subjects with a non-SAE related to the remedē system or implant procedure is also provided. Events are included if they occurred on or after the initial implant date through 2 years post implant. A subject may have both SAE and non-SAE events, so the participants with serious events cannot be added to the non-serious participants to get the total number of participants experiencing a related event. | Up to 2 years | 
| Epworth Sleepiness Scale Change From Baseline at 6 Months | Change = 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. | Baseline and 6 months on therapy | 
| Minnesota Living With Heart Failure Questionnaire Change From Baseline at 6 Months | Change = Month 6 score - Baseline score This questionnaire was for the N=46 patients diagnosed with heart failure. Scores can range from 0-105, with lower scores indicating better quality of life. | Baseline and 6 months on therapy | 
| Heart Failure Clinical Composite | The composite is determined according to the following definitions. Worsened: subject died; was hospitalized due to or associated with worsening HF; demonstrated worsening in NYHA class at last observation carried forward; moderate-marked worsening of patient global assessment score at last observation carried forward; or permanently discontinued therapy from the remedē System due to or associated with worsening HF. Improved: subject did not worsen (as defined above) and demonstrated improvement in NYHA class at last observation carried forward or moderate-marked improvement in patient global assessment score at last observation carried forward. Unchanged: patient was neither improved nor worsened. | 6 months on therapy | 
| Six-minute Hall Walk Test Change From Baseline at 6 Months | Change = Month 6 score - Baseline score | Baseline and 6 months on therapy | 
| NYHA Functional Class Improvement From Baseline to 6 Months | Shift in NYHA Class from baseline to 6 months NYHA Class I - Patients with cardiac disease but without resulting limitation of physical activity. Ordinary physical activity does not cause undue fatigue, palpitation, dyspnea or anginal pain. NYHA Class II - Patients with cardiac disease resulting in slight limitation of physical activity. They are comfortable at rest. Ordinary physical activity results in fatigue, palpitation, dyspnea or anginal pain. NYHA Class III - Patients with cardiac disease resulting in marked limitation of physical activity. They are comfortable at rest. Less than ordinary activity causes fatigue, palpitation, dyspnea or anginal pain. NYHA Class IV - Patients with cardiac disease resulting in inability to carry on any physical activity without discomfort. Symptoms of heart failure or the anginal syndrome may be present event at rest. If any physical activity is undertaken, discomfort increases. | Baseline and 6 months on therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sleep Disordered Breathing, Cheyne Stokes Respiration, Periodic Breathing, Sleep Apnea, Central Sleep Apnea