Central Sleep Apnea, Cheyne Stokes Respiration, Periodic Breathing, Sleep Apnea, Sleep Disordered Breathing
Conditions
Keywords
Sleep Disordered Breathing, Cheyne Stokes Respiration, Periodic Breathing, Sleep Apnea, Central Sleep Apnea
Brief summary
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.
Interventions
DEVICEremedē (TM) system
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.
Sponsors
Respicardia, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AHI Change From Baseline at 3 Months | Baseline and 3 months on therapy | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Epworth Sleepiness Scale Change From Baseline at 6 Months | Baseline and 6 months on therapy | 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. |
| Minnesota Living With Heart Failure Questionnaire Change From Baseline at 6 Months | Baseline and 6 months on therapy | 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. |
| Related Adverse Events | Up to 2 years | 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. |
| Six-minute Hall Walk Test Change From Baseline at 6 Months | Baseline and 6 months on therapy | Change = Month 6 score - Baseline score |
| NYHA Functional Class Improvement From Baseline to 6 Months | Baseline and 6 months on therapy | 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. |
| Heart Failure Clinical Composite | 6 months on therapy | 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. |
Countries
Germany, Italy, Poland, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Treatment Implantation of the remedē system which provides unilateral transvenous phrenic nerve stimulation therapy during sleep. | 57 |
| Total | 57 |
Baseline characteristics
| Characteristic | Treatment |
|---|---|
| Age, Continuous | 66.3 years STANDARD_DEVIATION 9.4 |
| Apnea-Hypopnea Index (AHI) | 49.1 events/hour STANDARD_DEVIATION 15 |
| Atrial Fibrillation No | 41 participants |
| Atrial Fibrillation Yes | 16 participants |
| Concomitant implantable device delivering therapy No | 28 participants |
| Concomitant implantable device delivering therapy Yes | 29 participants |
| Coronary Artery Disease No | 22 participants |
| Coronary Artery Disease Yes | 35 participants |
| Ejection Fraction | 29.6 percent STANDARD_DEVIATION 10.8 |
| Epworth Sleepiness Scale (ESS) | 8.6 units on a scale STANDARD_DEVIATION 4.4 |
| Heart failure No | 11 participants |
| Heart failure Yes | 46 participants |
| Hyperlipidemia No | 37 participants |
| Hyperlipidemia Yes | 20 participants |
| Hypertension No | 16 participants |
| Hypertension Yes | 41 participants |
| Minnesota Living with Heart Failure Questionnaire (MNLHF) | 41.4 units on a scale STANDARD_DEVIATION 18.9 |
| New York Heart Association (NYHA) Functional Class Class I | 4 participants |
| New York Heart Association (NYHA) Functional Class Class II | 28 participants |
| New York Heart Association (NYHA) Functional Class Class III | 13 participants |
| New York Heart Association (NYHA) Functional Class Class IV | 1 participants |
| New York Heart Association (NYHA) Functional Class Not applicable | 11 participants |
| Region of Enrollment Germany | 18 participants |
| Region of Enrollment Italy | 3 participants |
| Region of Enrollment Poland | 17 participants |
| Region of Enrollment United States | 19 participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 51 Participants |
| Six minute hall walk | 377.8 meters STANDARD_DEVIATION 144.5 |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 35 / 57 |
| serious Total, serious adverse events | 41 / 57 |
Outcome results
Primary
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.
Time frame: Baseline and 3 months on therapy
Population: The evaluable population includes subjects who completed a 3 Month post therapy initiation visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | AHI Change From Baseline at 3 Months | -27.1 events/hour | Standard Deviation 17.7 |
Comparison: The null hypothesis was that there would be no change in AHI from baseline.p-value: <0.001t-test, 2 sided
Secondary
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.
Time frame: Baseline and 6 months on therapy
Population: Subjects with baseline and 6 month data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Epworth Sleepiness Scale Change From Baseline at 6 Months | -2.0 units on a scale | Standard Deviation 4.3 |
Secondary
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.
Time frame: 6 months on therapy
Population: Evaluable subjects with heart failure at baseline.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Heart Failure Clinical Composite | Improved | 20 participants |
| Treatment | Heart Failure Clinical Composite | Unchanged | 9 participants |
| Treatment | Heart Failure Clinical Composite | Worsened | 8 participants |
Secondary
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.
Time frame: Baseline and 6 months on therapy
Population: Heart failure subjects with baseline and 6 month results.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Minnesota Living With Heart Failure Questionnaire Change From Baseline at 6 Months | -9.9 units on a scale | Standard Deviation 16.5 |
Secondary
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.
Time frame: Baseline and 6 months on therapy
Population: Heart failure subjects with 6 month data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | NYHA Functional Class Improvement From Baseline to 6 Months | Improved | 11 participants |
| Treatment | NYHA Functional Class Improvement From Baseline to 6 Months | No change | 25 participants |
| Treatment | NYHA Functional Class Improvement From Baseline to 6 Months | Worsened | 0 participants |
Secondary
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.
Time frame: Up to 2 years
Population: Subjects with an implant attempt.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Treatment | Related Adverse Events | Serious | 18 participants |
| Treatment | Related Adverse Events | Non-Serious | 23 participants |
Secondary
Six-minute Hall Walk Test Change From Baseline at 6 Months
Change = Month 6 score - Baseline score
Time frame: Baseline and 6 months on therapy
Population: Subjects with baseline and 6 month data.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Treatment | Six-minute Hall Walk Test Change From Baseline at 6 Months | -7.5 meters | Standard Deviation 58.7 |