Chronic Evaluation of Respicardia Therapy

• ClinicalTrials.gov Identifier: NCT01124370
• Recruitment Status: Completed
• First Posted: May 17, 2010
• Results First Posted: August 31, 2015
• Last Update Posted: May 16, 2016
• Sponsor: Respicardia, Inc.
• Information provided by (Responsible Party): Respicardia, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Sleep Disordered Breathing; Cheyne Stokes Respiration; Periodic Breathing; Sleep Apnea; Central Sleep Apnea	Device: remedē (TM) system	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 57 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Safety and Efficacy Evaluation of Respicardia Therapy for Central Sleep Apnea
• Study Start Date: May 2010
• Actual Primary Completion Date: August 2014
• Actual Study Completion Date: August 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment; 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; 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.; Other Names: Respicardia Therapy; Cardiac Concepts Therapy; (note: Respicardia was formerly Cardiac Concepts)

Outcome Measures

Primary Outcome Measures :

1. AHI Change From Baseline at 3 Months [ Time Frame: 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 Outcome Measures :

1. Related Adverse Events [ Time Frame: 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.
2. Epworth Sleepiness Scale Change From Baseline at 6 Months [ Time Frame: 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.
3. Minnesota Living With Heart Failure Questionnaire Change From Baseline at 6 Months [ Time Frame: 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.
4. Heart Failure Clinical Composite [ Time Frame: 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.

5. Six-minute Hall Walk Test Change From Baseline at 6 Months [ Time Frame: Baseline and 6 months on therapy ]
   Change = Month 6 score - Baseline score
6. NYHA Functional Class Improvement From Baseline to 6 Months [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, Nebraska

BryanLGH Heart Institute

Lincoln, Nebraska, United States, 68506

United States, Ohio

The Ohio State University

Columbus, Ohio, United States

United States, Pennsylvania

Lancaster Heart and Stroke Foundation

Lancaster, Pennsylvania, United States, 17602

United States, Tennessee

St. Thomas Heart

Nashville, Tennessee, United States

United States, Virginia

Sentara Cardiovascular Research Institute

Norfolk, Virginia, United States, 23507

Germany

Heart and Diabetes Center

Bad Oeynhausen, Germany

University of Kiel

Kiel, Germany

Köln University

Köln, Germany

St. Adolf-Stift Hospital

Reinbek, Germany

Italy

Policlinico di Monza-IRCCS

Monza, Italy

Poland

Jagiellonian University

Krakow, Poland

Medical Military Institute

Warsaw, Poland

4th Military Hospital

Wroclaw, Poland

Sponsors and Collaborators

Respicardia, Inc.

Investigators

• Principal Investigator: Piotr Ponikowski, MD; 4th Military Hospital, Poland
• Principal Investigator: William T Abraham, MD; Ohio State University

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Javaheri S, McKane SW, Cameron N, Germany RE, Malhotra A. In patients with heart failure the burden of central sleep apnea increases in the late sleep hours. Sleep. 2019 Jan 1;42(1). doi: 10.1093/sleep/zsy195.

Abraham WT, Jagielski D, Oldenburg O, Augostini R, Krueger S, Kolodziej A, Gutleben KJ, Khayat R, Merliss A, Harsch MR, Holcomb RG, Javaheri S, Ponikowski P; remedē Pilot Study Investigators. Phrenic nerve stimulation for the treatment of central sleep apnea. JACC Heart Fail. 2015 May;3(5):360-369. doi: 10.1016/j.jchf.2014.12.013. Epub 2015 Mar 11.

• Responsible Party: Respicardia, Inc.
• ClinicalTrials.gov Identifier: NCT01124370
• Other Study ID Numbers: Respicardia - Chronic Study I
• First Posted: May 17, 2010
• Results First Posted: August 31, 2015
• Last Update Posted: May 16, 2016
• Last Verified: April 2016

Keywords provided by Respicardia, Inc.:

Sleep Disordered Breathing; Cheyne Stokes Respiration; Periodic Breathing; Sleep Apnea; Central Sleep Apnea

Additional relevant MeSH terms:

Apnea; Sleep Apnea Syndromes; Respiratory Aspiration; Sleep Apnea, Central; Cheyne-Stokes Respiration; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases; Pathologic Processes