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Feasibility Study Results
The clinical value of Respiratory Rhythm Management was initially evaluated in a feasibility study designed to study acutely the effectiveness and safety of unilateral phrenic nerve stimulation in patients with periodic breathing. Patients received a temporary stimulation lead and then underwent two consecutive nights of sleep studies, one control night and one therapy night. Therapy was well tolerated and results showed significantly reduced episodes of Central Sleep Apnea and restored natural breathing.
Pilot Study Results
Safety and lasting effectiveness of the remedē® System was tested in a Pilot Study which analyzed the Apnea/Hypopnea Index (AHI) compared to baseline after three months of therapy and six months later. Results of patients with moderate to severe central sleep apnea show:
- Central Apnea Index (CAI) decreased by 84% – improved oxygenation and decreased arousals
- Apnea-Hypopnea Index decreased by 55% – associated with decreased mortality and ventricular arrhythmias
- Oxygen Desaturation Index improved by 52% – decreased inflammation, ischemia and sympathetic drive
- Arousals decreased by 35% – decreased norepinephrine release and sympathetic drive
- Rapid Eye Movement (REM) by 29% – associated with improved parasympathetic control and decreased sympathetic drive
- Abraham WT, Jagielski D, Oldenburg O, Augostini R, Krueger S, Kolodziej A, et al. Phrenic nerve stimulation for the treatment of central sleep apnea. J Am Coll Cardiol – Heart Fail. In press.
Pivotal Trial Results
The remedē System Pivotal Trial was a prospective, multi-center, randomized (1:1) controlled trial that enrolled patients with moderate to severe CSA based on PSGs scored by a blinded core laboratory.
PSG inclusion criteria:
- AHI ≥20
- CAI at least 50% of all apneas with at least 30 central apnea events
- Obstructive Apnea Index ≤20% of the total AHI
151 patients were enrolled at 31 centers in the US and Europe. All patients underwent system implantation and the Control group had therapy initiated after the 6-month effectiveness assessment.
- A significantly higher proportion of patients in the Treatment versus Control Group achieved a ≥50% AHI reduction (Primary Effectiveness Endpoint)
- A 91% 12-month freedom from serious AEs related to the implant procedure, remedē System or delivered therapy (Primary Safety Endpoint)
- A significantly greater improvement in the Treatment versus Control group in all secondary end-points hierarchically tested in the per-protocol population
- The consistency between favorable changes in sleep variables and quality of life measure demonstrates that the therapy produces improvements which are clinically meaningful
- Exploratory analyses have shown improvement in the heart failure cohort which are similar to those observed in the overall study population
Importantly, delivery of the therapy occurs throughout the night and is independent of patients’ adherence.
- Maria Rosa Costanzo, Piotr Ponikowski, Shahrokh Javaheri, Ralph Augostini, Lee Goldberg, Richard Holcomb, Andrew Kao, Rami N Khayat, Olaf Oldenburg, Christoph Stellbrink, William T Abraham, for the remedē System Pivotal Trial Study Group, Lancet 2016; 388: 974–82.