Impact of Head of Bed Elevation in Symptoms of Patients With Gastroesophageal Reflux Disease: a Randomized Single-blind Study

PROBLEM STATEMENT

Gastroesophageal reflux disease (GERD) is a clinical condition characterized by troublesome symptoms and medical complications as a result of reflux of gastric contents into the esophagus. GERD is diagnosed in 4% of primary care outpatient visits and the disease prevalence in Latin-America reaches 12-31%. Nocturnal symptoms have been found in 74% of patients with GERD and are a cause of significant quality of life impairment, when compared with general population and patients with GERD and daytime-only symptoms. Sleep interference secondary to nocturnal retrosternal burning has been associated to lower work productivity, even in patients being treated with proton pump inhibitors (PPI). Due to several physiological factors such as lack of conscious perception of symptoms, reduced salivation and a lower frequency of nocturnal swallowing, a significantly longer acid exposure overnight has been associated to the emergence of complications like esophagitis, more extra-esophageal symptoms and other illnesses such as asthma.

As a low-cost non pharmacological anti-reflux treatment for GERD, head of bed elevation (HBE) is nowadays a moderate-strength recommendation with low level of evidence. Clinical impact of this measure in patients with night-time symptoms remains unknown, due to inconsistent results and methodological limitations among different clinical trials; most of which were performed before the widespread use of proton pump inhibitors in clinical practice. Evidence from several non-randomized studies suggest that HBE could reduce esophageal acid exposure time and could decrease GERD symptoms; however, another study found no significant differences in those same outcomes. On the other hand, all randomized controlled clinical trials published this far show inconsistent results. A study published before widely accepted clinical use of PPI, revealed significant clinical and endoscopic improvement with HBE in patients with GERD and grade C-D esophagitis, when compared to controls. In contrast, a multi-centre clinical trial found no difference in symptom score or antacid use among groups allocated to HBE and control group. All cited studies have methodological limitations and heterogeneity in outcome assessments, which makes difficult conducting a meta-analysis with these data. No published studies evaluating impact of HBE in quality of life or work productivity were found.

SAMPLE SIZE CALCULATION

Sample size was estimated based on the hypothesis that HBE would produce a difference of at least 10% in RDQ and SF-36 scores. Effect size (Cohen d) was calculated as 0,49, keeping in mind an RDQ mean and standard deviation of 3,3±1,0 previously found in Spanish population with symptomatic GERD. An SF-36 mean and standard deviation of 56,9±20,3 reported in Italian population in medical therapy with PPI were also taken into account. The minimally important difference selection was chosen based on the assumption that any difference smaller than 10% would have no clinical relevance. Based on this data, 14 patients per group would yield a power greater than 80% for detection of a minimally important difference as large as or larger than 0,6 points in RDQ questionnaire (range: 1 to 6) and 10 points in SF-36 questionnaire (range: 0 to 100), when using a paired t test. For a complementary analysis of this trial, by using a McNemar test, effect size was recalculated based on published clinical trial data from pre-omeprazole era, according to which 58,8% and 28,6% of patients assigned to placebo improved gastroesophageal reflux symptoms with and without 20 cm HBE, respectively. Based on this data, and maintaining a statistical power of 80%, required sample size was adjusted to a total of 34 patients. G*Power 3.1.9.2 software (Universität Düsseldorf, Düsseldorf, Germany). Finally, estimated sample size was incremented by 20% to avoid that eventual losses of follow-up may alter study power. Therefore, final sample size was 42 patients, 21 patients per group.