Randomized sham‐controlled trial evaluating efficacy and safety of endoscopic gastric plication for primary obesity: The ESSENTIAL trial

Abstract

Objective: Evaluate safety and efficacy of the pose TM procedure for obesity treatment.Methods: Subjects with Class I to II obesity were randomized (2:1) to receive active or sham procedure, after each investigator performed unblinded lead-in cases. All subjects were provided low-intensity lifestyle therapy. Efficacy end points were the mean difference in percent total body weight loss (%TBWL) at 12 months between randomized groups, and responder rate achieving 5% TBWL. The primary safety end point was incidence of reported adverse events.Results: Three hundred thirty-two subjects were randomized (active, n 5 221; sham, n 5 111); thirty-four subjects were included in the unblinded lead-in cohort. Twelve-month results were mean TBWL 7.0 6 7.4% in lead-in, 4.95 6 7.04% in active, and 1.38 6 5.58% in sham groups, respectively. Responder rate was 41.55% in active and 22.11% in sham groups, respectively (P < 0.0001); mean responder result was 11.5% TBWL. The differences observed between active and sham groups for co-primary end points were statistically significant (P < 0.0001); however, super superiority margin as set forth in the study design was not met. No unanticipated adverse events or deaths occurred. Procedure-related serious adverse event rates were 5.0% (active) and 0.9% (sham), P 5 0.068. Conclusions:The pose procedure was safe and resulted in statistically significant and clinically meaningful weight loss over sham through 1 year.

Randomized sham-controlled trials in endoscopy: a systematic review and meta-analysis of adverse events

“…Finally, some sham controls with partial cross-over design decrease scientific validity by introducing perverse incentives. For example, in the ESSENTIAL trial, subjects were randomized to an endoscopic obesity therapy or a sham procedure, with a partial cross-over for patients initially allocated to the sham arm 23 . The only subjects eligible for the cross-over study were those who did not lose weight.…”

“…It is well known that this adverse event can be associated with significant morbidity and cost to the healthcare system. Studies investigating novel obesity and GERD treatments report placement of large Bougies up to 54F being advanced into the esophagus and rotated at regular intervals to simulate the study intervention, device placement and maneuvering 23,33 . This carries the risk of mucosal abrasion, bleeding, aspiration, and perforation.…”

“…*3 studies in (A) 35,58,60 and 7 studies in (B) 23,35,50,52,53,58,60 were excluded from these figures because the number of events was higher than the total number of subjects or there were zero adverse events reported in both sham and treatment AE categories.…”

Endoscopic bariatric and metabolic therapies: Another tool for the management of diabetes and obesity

“…However, when POSE was compared to sham procedure in the ESSENTIAL trial, mean (±SD) TBWL was reported to be only 4.95 ± 7.04% (n = 220) . These less robust findings could be attributed to a lack of lifestyle intervention in the entire study population, because the mean weight loss in the POSE group was 3.6‐fold that of the sham group . This highlights the importance of intensive lifestyle modifications in conjunction with endoscopic bariatric interventions.…”

“…Primary Obesity Surgery Endolumenal is another gastric remodeling procedure that uses the FDA‐approved Incisionless Operating Platform (IOP; USGI Medical, San Clemente, California) to place 11 to 13 plications in the fundus and distal body using suture anchors. It is hypothesized that these transmural plications function to reduce postprandial accommodation of the fundus to induce early satiety and cause dysmotility of the antrum to delay gastric emptying to ultimately reduce caloric intake . A study by Espinós et al demonstrated a decrease in caloric intake from 901 kcal at baseline to 473 and 574 kcal 2 and 6 months after the procedure, respectively ( P < 0.001; n = 18).…”