The role of sham continuous positive airway pressure as a placebo in controlled trials: Best Apnea Interventions for Research Trial

Abstract

Study Objectives The main objective of this study was to evaluate the role of sham continuous positive airway pressure (CPAP) compared to conservative medical therapy (CMT) as a control arm in the Best Apnea Interventions for Research (BestAIR) study by assessing differences in subjectively and objectively measured outcomes, adverse events, adherence, and retention rates. Methods BestAIR is a clinical trial aimed to identify important design features for future randomized controlled trials of CPAP. Participants with obstructive sleep apnea were randomized to one of four groups; two control arms (CMT, sham-CPAP) and two active CPAP arms (with and without behavioral interventions). Blood pressure and health-related quality of life outcomes were assessed at baseline, 6 and 12 months. Study outcomes, retention, and adverse event rates were compared between the two control arms. Sham-CPAP adherence and self-efficacy were also compared to active-CPAP adherence (without behavioral intervention). Results Our sample included 86 individuals in the control arms and 42 participants in the active-CPAP arm. There were no differences in longitudinal profiles in blood pressure, health-related quality of life outcomes, dropout rates, or adverse events in sham-CPAP group compared to CMT-only group (all ps > 0.05); standardized differences were generally small and with inconsistent directionality across measurements. When compared to active-CPAP, sham-CPAP was associated with 93 fewer minutes/night of usage over 12 months (p = 0.007) and lower outcome expectations (p < 0.05). Conclusion We observed no evidence of differences in objectively or subjectively measured outcomes with the use of sham-CPAP compared to CMT group. The lower adherence on sham-CPAP and poorer self-efficacy compared to active-CPAP may suggest differences in perceived benefit. Registration NCT 01261390 Best Apnea Interventions for Research (BestAIR) www.clinicaltrials.gov

Propensity score weighting for covariate adjustment in randomized clinical trials

“…The Best Apnea Interventions for Research (BestAIR) trial is an individually randomized, parallel‐group trial designed to evaluate the effect of continuous positive airway pressure (CPAP) treatment on the health outcomes of patients with high cardiovascular disease risk and obstructive sleep apnea but without severe sleepiness 42 . Patients were recruited from outpatient clinics at three medical centers in Boston, Massachusetts, and were randomized in a 1:1:1:1 ratio to receive conservative medical therapy (CMT), CMT plus sham CPAP (sham CPAP is a modified device that closely mimics the active CPAP and serves as the placebo for CPAP RCTs 43 ), CMT plus CPAP, or CMT plus CPAP plus motivational enhancement (ME). We follow the study protocol and pool two subarms into the combined control group (CMT, CMT plus sham CPAP) and the rest subarms into the combined CPAP or active intervention group.…”

Continuous positive airway pressure improves blood pressure and serum cardiovascular biomarkers in obstructive sleep apnoea and hypertension

“…Patients having three or more medications regardless of their clinic BP were recruited in the study, and 27% (table 1) had ambulatory 24-h BP control within the goal and did not fulfil the definition of resistant hypertension (supplementary material) [11]. Our study used controls without CPAP treatment as the comparison group rather than sham-CPAP, in view of the likelihood of poor adherence to sham-CPAP and its lack of a genuine effect on blinding [39]. Follow-up of participants on CPAP has not been extended for further measurements of biomarkers or the occurrence of cardiovascular events.…”

Sleep Apnea and Fetal Growth Restriction (SAFER) study: protocol for a pragmatic randomised clinical trial of positive airway pressure as an antenatal therapy for fetal growth restriction in maternal obstructive sleep apnoea

“…While this could minimise bias in evaluating the effect of PAP, wearing an ineffective mask does increase the risk of discomfort and sleep disturbances for the control group, which potentially biases the results toward the active group. A recent study 53 demonstrated that there was no difference in outcome between sham PAP and a device-free control; however, most subjects in the sham PAP group guessed correctly that they were receiving the placebo intervention.…”

“…Estimates of fetal weight were all based on the Hadlock formula using the standard biometric parameters (biparietal diameter, head circumference, abdominal circumference, femur length) [52,53]. 50 51 However, when converting fetal weight to a calculated percentile, this must reference a 'population or customized standard'.…”