Morpheus: Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF

Sponsor

Medtronic Bakken Research Center (Industry)

Overall Status

Completed

CT.gov ID

NCT00551499

Collaborator

(none)

Enrollment

Locations

Arms

Actual Duration (Months)

Patients Per Site

1.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The primary objective of this study is to compare the Apnea- Hypopnea Index in HF patients with concomitant CSA, after 12 weeks of CRT alone to CRT in combination with one night of overdrive pacing. Secondary objectives are to evaluate the effects of a single night of overdrive pacing applied after 12 weeks of CRT vs. CRT alone on breathing events, sleeping events, and neurohormonal markers. An additional secondary objective of the study is to compare the efficacy of CRT in HF patients with concomitant CSA to HF patients without concomitant CSA.

Condition or Disease	Intervention/Treatment	Phase
Heart Failure Central Sleep Apnea	Device: CRT + AOP	Phase 4

Detailed Description

Sleep apnea is a common and often undiagnosed disorder associated with substantial cardiovascular morbidity and mortality. In recent years studies have been published presenting the relationship between heart failure (HF) and central sleep apnea (CSA). CSA associated with Cheyne-Stokes respiration is a form of periodic breathing in which central apneas and hypopnea alternate with periods of hyperventilation, characterized by a regular crescendo-decrescendo oscillation of tidal volume, which is thought to be caused by dysfunction of central respiratory control. Unlike, obstructive sleep apnea (OSA), CSA likely arises as a consequence of HF.Since 2002, several results have reported on the benefit of atrial overdrive (AOP) pacing in patients suffering from sleep apnea. These results could not be confirmed for obstructive sleep apnea in several subsequent studies. Cardiac resynchronization therapy (CRT) has been proposed as another potential therapeutic pacing approach for CSA by two recently published investigations.The combined therapeutic impact of AOP and CRT (CRT+AOP) so far has not been investigated.We aimed to evaluate the effect of CRT alone and CRT+AOP on CSA in patients with CHF.

Study Design

Study Type:

Interventional

Actual Enrollment :

44 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

Comparing effect of CRT in patients with and without CSA + comparing effect of AOP in combination with CRT in patients with CSAComparing effect of CRT in patients with and without CSA + comparing effect of AOP in combination with CRT in patients with CSA

Masking:

Single (Participant)

Primary Purpose:

Treatment

Official Title:

Cardiac Resynchronisation Therapy in Combination With Overdrive Pacing in the Treatment of Central Sleep Apnea in CHF

Actual Study Start Date :

Jun 1, 2005

Actual Primary Completion Date :

Dec 1, 2006

Actual Study Completion Date :

Dec 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
No Intervention: CRT for patients with CSA Patients suffering from HF with central Sleep Apnea (CSA) programmed to DDD/45 (CRT) for 12 weeks. Intervention is CRT.
Active Comparator: CRT + AOP for patients with CSA Patients suffering from HF with central Sleep Apnea programmed to DDD/+15 bpm nocturnal rate (CRT + AOP) for 12 weeks. Intervention is the AOP in addition to CRT.	Device: CRT + AOP The CSA group will undergo 2 sleep evaluation on two consecutive nights, during which the device will be programmed according to the randomization scheme (one night CRT, DDD/45 and the other CRT, DDD/15 bpm over mean nocturnal heart rate). The mean nocturnal heart rate over the last week is derived from the device memory.

Arm

Intervention/Treatment

No Intervention: CRT for patients with CSA

Patients suffering from HF with central Sleep Apnea (CSA) programmed to DDD/45 (CRT) for 12 weeks. Intervention is CRT.

Active Comparator: CRT + AOP for patients with CSA

Patients suffering from HF with central Sleep Apnea programmed to DDD/+15 bpm nocturnal rate (CRT + AOP) for 12 weeks. Intervention is the AOP in addition to CRT.

Device: CRT + AOP

The CSA group will undergo 2 sleep evaluation on two consecutive nights, during which the device will be programmed according to the randomization scheme (one night CRT, DDD/45 and the other CRT, DDD/15 bpm over mean nocturnal heart rate). The mean nocturnal heart rate over the last week is derived from the device memory.

Outcome Measures

Primary Outcome Measures

AHI [12 weeks]
To demonstrate that a single night of overdrive pacing applied after 12 weeks of cardiac resynchronization therapy in comparison to cardiac resynchronization alone will improve sleep apnea as measured by Apnea- hypopnea- index (AHI)

Secondary Outcome Measures

NYHA class [12 weeks]
To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on NYHA
Echocardiographic parameter [12 weeks]
To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on LVEF
Neurohormonal parameter [12 weeks]
To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on neurohormonal marker NT pro-BNP
Clinical parameter [12 weeks]
To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on the clinical parameter VO2max
Quality of Life [12 weeks]
To evaluate the effects of nocturnal overdrive pacing applied after 12 weeks of CRT vs. CRT alone on Quality of life

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients with documented clinical history of symptomatic but stable congestive heart failure, NYHA III or NYHA IV, of at least six weeks duration.
Patient has an indication for a CRT device, or patients with previous pacemaker indication, except Sick Sinus Syndrome, and currently in need for an upgrade to a CRT device
Patient is scheduled for the implantation of a CRT device
Patient is over 18 years of age
Patient provides Informed Consent

Exclusion Criteria:

Inability to complete overnight sleep study as specified by the protocol
Myocardial infarction or coronary revascularization procedure within 2 calendar months prior to enrollment
Planned or strong likelihood of cardiac surgery within 4 months following enrollment
A spirometric confirmation of obstructive lung disease
Evidence of obstructive sleep apnea at baseline polysomnography
Body mass index >30 kg/m²
Pregnant women

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Medizinische Klinik und Poliklinik II Universitätsklinikum, University of Bonn	Bonn		Germany	53105
2	Georg-August-Universität, Department of Cardiology and Pneumology	Göttingen		Germany	D-37075

Sponsors and Collaborators

Medtronic Bakken Research Center

Investigators

Principal Investigator: S Andreas, Prof. Dr, Georg-August-Universität, Göttingen, Department of Cardiology and Pneumology, Robert-Koch Str. 40, 37075 Göttingen, Germany