Evaluation of sham-CPAP as a placebo in CPAP intervention studies

Abstract

Study objectives: To evaluate the use of sham-continuous positive airway pressure (CPAP) treatment as a placebo intervention.

Design and setting: Analysis of polysomnograms performed in fixed order without sham-CPAP and on the first night of the sham-CPAP intervention in participants in the CPAP Apnea Trial North American Program (CATNAP), a randomized, placebo controlled trial evaluating the effects of CPAP treatment on daytime function in adults with newly diagnosed mild to moderate obstructive sleep apnea (apnea hypopnea index (AHI) 5-30).

Participants: The first 104 CATNAP participants randomized to the sham-CPAP intervention arm.

Measurements and results: Compared to the polysomnographic measures without sham-CPAP, the study on the first night with sham-CPAP had statistically significant differences that suggested a decrease in sleep quality: decreased sleep efficiency, increased arousal index, increased time in stage 1 NREM sleep, and prolonged latency to REM sleep. However, all of these differences had a relatively small effect size. Compared to the polysomnogram without sham-CPAP, the number of hypopneas on the sham-CPAP polysomnogram was significantly increased and the number of apneas significantly decreased. Relatively minor differences in AHI with and without sham-CPAP were present and were dependent on the criteria used to score hypopneas.

Conclusion: Comparison of polysomnograms with and without sham-CPAP revealed differences that, although statistically significant, were small in magnitude and had relatively low effect sizes suggesting minimal clinical significance. The results support the use of sham-CPAP as a placebo intervention in trials evaluating the effects of CPAP treatment in patients with obstructive sleep apnea.

Clinical trial information: This paper was a secondary analysis of clinical trial data. CATNAP: CPAP Apnea Trial North American Program, the trial from which the data were obtained, is registered with clinicaltrial.gov. Registration #NCT00089752.

Figure 1

Exhalation connectors inserted between the mask interface and tubing in the active and sham-CPAP circuits. Figure 1a shows the inner part of the exhalation connector used in the active CPAP (left) and sham-CPAP (right) circuits. The inner part of the exhalation connector used in the sham-CPAP circuit had an enlarged port for expiratory airflow. This modification was not noticeable when the connector was fully assembled (Fig. 1b, active connector on left, sham-CPAP connector on right).

Figure 2

Orifice restrictor used in the sham-CPAP circuit. During the sham-CPAP polysomnograms, the orifice restrictor was inserted between the laboratory's remotely controlled CPAP machine and tubing. A port on the side of the orifice restrictor was occluded by a white plastic cap. For the device that the participants used at home, the orifice restrictor was located within the CPAP machine. Placement of the orifice restrictor and exhalation connector with enlarged air leak into the CPAP circuit, with the machine set at 10 cm H₂O, resulted in a pressure at the mask interface less than 1 cm H₂O.