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Comparison of CPAP vs. C-Flex
for the Treatment of Obstructive Sleep Apnea
A Summary of Two Independent Studies

C-Flex therapy is defined as CPAP with the C-Flex therapy feature enabled.
 Comparison of CPAP vs. C-Flex
for the Treatment of Obstructive Sleep Apnea

Introduction

Despite nearly 100% efficacy as a treatment for obstructive sleep apnea (OSA), conventional continuous positive airway
pressure (CPAP) adherence is known to be only 40% to 70%. The sensation of being unable to fully exhale against CPAP
or pressure intolerance is a frequent complaint of non-adherent patients. A novel positive pressure mode, C-Flex, was
developed to provide a base pressure to abolish pharyngeal collapse, as well as decrease the cumulative pressure during
exhalation. C-Flex therapy allows for pressure reduction at the start of exhalation followed by a sinusoidal rise in pressure as
exhalation ends.

Two independent studies were performed by board certified sleep clinicians in AASM accredited sleep centers comparing
C-Flex to CPAP. The first study was conducted at Lehigh Valley Hospital Sleep Disorder Center in Allentown, PA, under
the direction of principal investigator Dr. Richard Strobel. The second study was conducted at the Swedish Sleep Medicine
Institute at Swedish Medical Center in Seattle, WA, under the direction of principal investigator Dr. Daniel Loube.

C-Flex Description

C-Flex represents a revolutionary new method for delivering positive airway pressure (PAP) for the treatment of
obstructive sleep apnea (OSA). A typical complaint by those using conventional CPAP is that it is difficult to breathe out
against continuous positive pressure. This often results in short usage patterns and frequent awakenings, resulting in sleep
fragmentation and occasional discontinuation of therapy. C-Flex is designed to provide pressure relief during expiration,
while maintaining optimal pneumatic splinting for effective therapy. To establish the optimal C-Flex pressure, C-Flex
therapy is titrated in the same way as conventional CPAP. However, during use, C-Flex technology monitors the patients
airflow during expiration and reduces expiratory pressure proportional to expiratory flow. The relief pressure varies on a
breath-to-breath basis, depending on the actual patient airflow. Prior to the end of expiration and start of each inspiration,
there is a return to the prescribed therapeutic CPAP pressure, providing optimal therapeutic support to the airway. The figure
below shows a schematic representation of patient flow and the resulting pressure delivered with C-Flex. Expiratory pressure
relief during exhalation is shown, with the pressure returning to base pressure prior to the initiation of inspiration.

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Purpose

The aim of these studies was to assess whether: 1) C-Flex is an effective method to treat adult OSA, and 2) the C-Flex
therapy pressure profile minimizes sleep apnea and provides sleep quality that is equivalent to standard treatment.
Parameters assessed include Apnea Hypopnea Index (AHI), oxygen saturation (SpO2), sleep efficiency (SE%), arousal index
(AI), and snoring index.

STUDY 1 LEHIGH VALLEY HOSPITAL, ALLENTOWN, PA

Methods

The study was performed under an IRB approved protocol. All patients provided informed consent. The study population
included 30 individuals on CPAP therapy for at least six months of clinically demonstrated successful therapy. Inclusion
criteria were age 18 years, diagnosis of OSA/H by PSG and successful titration PSG for clinically effective CPAP within
the past year. Exclusion criteria included inability to wear the mask, excessive arousals or sleep disturbance associated
with other sleep problems, tracheotomy, use of supplemental oxygen during sleep, hospitalization within the past three
months (for cardiac or pulmonary disease), upper airway, throat, or nose surgery, psychiatric disorders, or restrictive lung
disorders (e.g., neuro-muscular or muscular-skeletal). Subjects underwent a single night of polysomnography (PSG) in
a single-blind, non-randomized split format, receiving CPAP and C-Flex therapy. CPAP and each of the three C-Flex
comfort levels (1 minimum, 2 moderate, and 3 maximum) were studied for equal time periods of 60 minutes in
30-minute increments.

Summary of Results

The data shows that C-Flex provides therapy that is as, if not more, effective as traditional CPAP. C-Flex produced similar
or better AHI compared to that seen with CPAP. All three levels of C-Flex produced statistically significant improvement
in sleep efficiency, as compared to conventional CPAP. For arousal index, C-Flex levels 1 and 3, compared to CPAP,
demonstrated statistically significant improvements. There was no statistically significant difference between CPAP
and C-Flex for oxygen saturation or snore index. C-Flex therapy provided successful positive airway pressure therapy.
The C-Flex results were comparable to the CPAP results.

Statistical Analysis

CPAP followed by three levels of C-Flex therapy in two non-randomized rounds, resulting in eight segments, were
evaluated. CPAP was always given first followed by C-Flex levels 1, 2, and 3. The analysis was done by the mixed
models procedure in SAS. The variables analyzed include apnea-hypopnea index (AHI), oxygen saturation (Sp02),
sleep efficiency (SE%), arousal index (AI), and snore index (Snore). Patient age and body mass index (BMI) were
also evaluated. Statistical significance was assessed at a P-value 0.10.

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 Descriptive Statistics for AHI, Sp02, SEI, AI, and Snore
The following tables and graphs illustrate the descriptive statistics.

Apnea Hypopnea Index (AHI)

Therapy Mean SD
CPAP 2.71 5.96
C-Flex 1 2.95 7.05
C-Flex 2 2.54 6.01
C-Flex 3 2.61 6.92

Oxygen Saturation (Sp02)

Therapy Mean SD
CPAP 93% 3%
C-Flex 1 94% 3%
C-Flex 2 93% 4%
C-Flex 3 94% 3%

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Sleep Efficiency (SE)

Therapy Mean SD
CPAP 0.88 0.16
C-Flex 1 0.92 0.11
C-Flex 2 0.91 0.13
C-Flex 3 0.90 0.17

Arousal Index (AI)

Therapy Mean SD
CPAP 16.14 19.76
C-Flex 1 12.40 15.13
C-Flex 2 11.32 14.90
C-Flex 3 9.50 10.30

These results indicate there is a statistically significant difference between CPAP and C-Flex levels 1 and 3 for AI.
The analysis of AI demonstrated significant improvements using C-Flex levels 1 and 3 compared to conventional
CPAP [C-Flex 1 (P=0.0648), C-Flex 2 (P=0.1493) and C-Flex 3 (P=0.0054)].

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 Snore

Therapy Mean SD
CPAP 62.5 102.93
C-Flex 1 59.9 107.94
C-Flex 2 59.02 108.05
C-Flex 3 53.58 100.15

There were no statistically significant differences between CPAP and C-Flex for the snore analysis, although the
comparison with C-Flex 2 and C-Flex 3 were close to significance (C-Flex 2 and CPAP, p = 0.1318 and C-Flex 3
and CPAP, p = 0.1239).

Conclusion

When compared to conventional CPAP, C-Flex at all three comfort levels is either equivalent to or superior than
conventional CPAP. There were no statistically significant differences between CPAP and C-Flex for snore,
apnea/hypopnea index, and oxygen saturation. For sleep efficiency, there were statistically significant improvements
seenat all three C-Flex comfort levels and, for arousal index, there were statistically significant improvements seen at
C-Flex comfort levels 1 and 3 when compared to CPAP.

Based on this analysis, C-Flex is as equivalent or superior than CPAP in reducing sleep disordered breathing events
and improving sleep efficiency in patients with obstructive sleep apnea/hypopnea syndrome.

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STUDY 2 SWEDISH MEDICAL CENTER, SEATTLE, WA
Methods

Study was performed under an IRB approved protocol, after subjects had signed informed consent. Prospective, randomized
double-blind study of 16 patients recently diagnosed with OSA who received a successful CPAP titration study. Patients
with other concomitant sleep disorders were excluded. OSA patients had an apnea/hypopnea index (AHI) > 10 events/hr
and did not have predominately REM-related or position dependent OSA. These patients underwent a split-night, in-lab
titration study during which CPAP and C-Flex therapy were compared. C-Flex expiratory pressure relief was applied at
various settings and each was compared to CPAP with respect to the AHI, total arousal index (AI), sleep efficiency (SE)
and other measurements derived from nocturnal polysomnography. Results were compared between conventional CPAP
and C-Flex and pressure relief settings using ANOVA statistical methods and linear mixed effects.

Summary of Results

These data demonstrate that there is no statistically significant difference in the AHI, AI, or sleep efficiency for OSA
patients using CPAP or C-Flex at each of the pressure relief settings.

Baseline CPAP C-Flex 1 C-Flex 2 C-Flex 3

AHI 40.3 5.1 5.5 4.6 6.8

( 26.2) ( 5.7) ( 9.8) ( 9.4) ( 11.4)

SE 80.2 92.7 94.9 92.1 88.0

( 13.4) ( 9.4) ( 8.3) ( 17.7) ( 21.0)

AI 36.2 19.4 10.5 15.4 20.4

( 13.0) ( 18.9) ( 9.0) ( 23.4) ( 20.0)

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Conclusion

There is no statistically significant difference between CPAP and C-Flex at any of the pressure relief settings, for AHI,
sleep efficiency, or arousal index. C-Flex is as effective as CPAP in abolishing obstructive respiratory events and has
the same immediate effect on sleep.

C-Flex therapy allows for pressure reduction during exhalation without recurrence of obstructive respiratory events
during sleep. Decreased mean mask pressure with the same therapeutic effect suggests possible advantage to adult OSA
patients who are non-compliant with CPAP because of expiratory pressure intolerance.

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