Nonresorbable copolymer implantation for gastroesophageal reflux disease: A randomized sham-controlled multicenter trial
2005; Elsevier BV; Volume: 128; Issue: 3 Linguagem: Inglês
10.1053/j.gastro.2004.12.005
ISSN1528-0012
AutoresJacques Devière, Guido Costamagna, Horst Neuhaus, Winfried A. Voderholzer, Hubert Louis, Andrea Tringali, Michele Marchese, Thomas Fiedler, Patrick Darb-Esfahani, Brigitte Schumacher,
Tópico(s)Helicobacter pylori-related gastroenterology studies
ResumoBackground & Aims: This aim was to determine whether endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA) is a more effective therapy for gastroesophageal reflux disease (GERD) than a sham procedure. Methods: In a randomized, single-blind, prospective, multicenter clinical trial, 64 patients with GERD were enrolled whose symptoms were well controlled by proton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy. Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedure consisting of standard upper endoscopy. Patients in both groups with unsatisfactory symptom relief after 3 months were eligible for re-treatment by Enteryx implantation. The primary study end point was ≥50% reduction in PPI use. Secondary end points included ≥50% improvement in GERD score and the proportion of patients not undergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6 months. Results: The percentage of Enteryx-treated patients achieving a ≥50% reduction in PPI use (81%) was greater than that of the sham group (53%), with a rate ratio of 1.52 (confidence interval [CI], 1.06–2.28; P = .023). A higher proportion of the Enteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI, 1.03–2.80; P = .033). GERD health-related quality of life heartburn score improvement ≥50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rate ratio, 3.05; CI, 1.55–6.33; P < .001). More Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23–9.29; P < .001). Conclusions: Enteryx implantation more effectively reduces PPI dependency and alleviates GERD symptoms than a sham procedure. Background & Aims: This aim was to determine whether endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA) is a more effective therapy for gastroesophageal reflux disease (GERD) than a sham procedure. Methods: In a randomized, single-blind, prospective, multicenter clinical trial, 64 patients with GERD were enrolled whose symptoms were well controlled by proton pump inhibitor (PPI) therapy and rapidly recurred after cessation of PPI therapy. Thirty-two patients were assigned to Enteryx implantation and 32 to a sham procedure consisting of standard upper endoscopy. Patients in both groups with unsatisfactory symptom relief after 3 months were eligible for re-treatment by Enteryx implantation. The primary study end point was ≥50% reduction in PPI use. Secondary end points included ≥50% improvement in GERD score and the proportion of patients not undergoing re-treatment procedure. Follow-up evaluations were performed at 3 and 6 months. Results: The percentage of Enteryx-treated patients achieving a ≥50% reduction in PPI use (81%) was greater than that of the sham group (53%), with a rate ratio of 1.52 (confidence interval [CI], 1.06–2.28; P = .023). A higher proportion of the Enteryx (68%) than sham group (41%) ceased PPI use completely (rate ratio, 1.67; CI, 1.03–2.80; P = .033). GERD health-related quality of life heartburn score improvement ≥50% was achieved by 67% of the Enteryx group versus 22% of the sham group (rate ratio, 3.05; CI, 1.55–6.33; P < .001). More Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (rate ratio, 4.33; CI, 2.23–9.29; P < .001). Conclusions: Enteryx implantation more effectively reduces PPI dependency and alleviates GERD symptoms than a sham procedure. Minimally invasive endoluminal procedures for gastroesophageal reflux disease (GERD) are designed to provide long-lasting symptom relief and abolish or lessen medication dependency.1Johnson D.A. Endoscopic therapy for GERD—baking, sewing, or stuffing: an evidence-based perspective.Rev Gastroenterol Disord. 2003; 3: 142-149PubMed Google Scholar Several endoluminal modalities have now been introduced into clinical practice.2Triadafilopoulos G. DiBaise J.K. Nostrant T.T. Stollman N.H. Anderson P.K. Wolfe M.M. Rothstein R.I. Wo J.M. Corley D.A. Patti M.G. Antignano L.V. Goff J.S. Edmundowicz S.A. Castell D.O. Rabine J.C. Kim M.S. Utley D.S. The Stretta procedure for the treatment of GERD 6 and 12 month follow-up of the U.S. open label trial.Gastrointest Endosc. 2002; 55: 149-156Abstract Full Text Full Text PDF PubMed Scopus (263) Google Scholar, 3Johnson D.A. Ganz R. Aisenberg J. Cohen L.B. Devière J. Foley T.R. Haber G.B. Peters J.H. Lehman G.A. Endoscopic implantation of Enteryx for treatment of GERD 12-month results of a prospective, multicenter trial.Am J Gastroenterol. 2003; 98: 1921-1930Crossref PubMed Scopus (131) Google Scholar, 4Mahmood Z. McMahon B.P. Arfin Q. Byrne P.J. Reynolds J.V. Murphy E.M. Weir D.G. Endocinch therapy for gastro-oesophageal reflux disease a one year prospective follow up.Gut. 2003; 52: 34-39Crossref PubMed Scopus (156) Google Scholar, 5Fockens P. Bruno M.J. Gabbrielli A. Odegaard S. Hatlebakk J. Allescher H.D. Rosch T. Rhodes M. Bastid C. Rey J. Boyer J. Muehldorffer S. van den Hombergh U. Costamagna G. Endoscopic augmentation of the lower esophageal sphincter for the treatment of gastroesophageal reflux disease multicenter study of the Gatekeeper Reflux Repair System.Endoscopy. 2004; 36: 682-689Crossref PubMed Scopus (82) Google Scholar, 6Pleskow D. Rothstein R. Lo S. Hawes R. Kozarek R. Haber G. Gostout C. Lembo A. Endoscopic full-thickness plication for the treatment of GERD a multicenter trial.Gastrointest Endosc. 2004; 59: 163-171Abstract Full Text Full Text PDF PubMed Scopus (113) Google Scholar Among these are lower esophageal sphincter augmentation via endoscopic implantation of a biocompatible nonresorbable copolymer (Enteryx; Boston Scientific Corp, Natick, MA).7Peters J.H. Silverman D.E. Stein A. Lower esophageal sphincter injection of a biocompatible polymer accuracy of implantation assessed by esophagectomy.Surg Endosc. 2003; 17: 547-550Crossref PubMed Scopus (15) Google Scholar The copolymer is injected as a nonviscous liquid and rapidly forms a spongy solid in situ. By 3–6 months, the implant has been shown to undergo fibrous encapsulation in a porcine model.8Mason R.J. Hughes M. Lehman G.A. Chiao G. Devière J. Silverman D.E. DeMeester T.R. Peters J.H. Endoscopic augmentation of the cardia with a biocompatible injectable polymer (Enteryx) in a porcine model.Surg Endosc. 2002; 16: 386-391Crossref PubMed Scopus (74) Google Scholar The durability of the implant for at least 3 years has been demonstrated by spiral computed tomography in a small clinical study.9Louis H. van Gansbeke D. Silverman D. Devière J. Three years follow-up for initial GERD patients injected with EVOH polymer.Gastroenterology. 2003; 124 (abstr): A419Abstract Full Text PDF Google Scholar Lower esophageal sphincter augmentation with Enteryx is believed to derive its effectiveness by modifying the distensibility and compliance at the cardioesophageal junction.8Mason R.J. Hughes M. Lehman G.A. Chiao G. Devière J. Silverman D.E. DeMeester T.R. Peters J.H. Endoscopic augmentation of the cardia with a biocompatible injectable polymer (Enteryx) in a porcine model.Surg Endosc. 2002; 16: 386-391Crossref PubMed Scopus (74) Google ScholarClinical results of Enteryx implantation have been favorable.10Devière J. Pastorelli A. Louis H. de Maertelaer V. Lehman G. Cicala M. Le Moine O. Silverman D. Costamagna G. Endoscopic implantation of a biopolymer in the lower esophageal sphincter for gastroesophageal reflux a pilot study.Gastrointest Endosc. 2002; 55: 335-341Abstract Full Text Full Text PDF PubMed Scopus (110) Google Scholar, 11Johnson D.A. Ganz R. Aisenberg J. Cohen L.B. Devière J. Foley T.R. Haber G.B. Peters J.H. Lehman G.A. Endoscopic, deep mural implantation of enteryx for the treatment of GERD 6-month follow-up of a multicenter trial.Am J Gastroenterol. 2003; 98: 250-258Crossref PubMed Scopus (100) Google Scholar In 2 prospective multicenter cohort trials involving 178 total patients followed up to 12 months, the procedure reduced use of proton pump inhibitors (PPIs) and alleviated symptoms in most patients, and no major complications were encountered.3Johnson D.A. Ganz R. Aisenberg J. Cohen L.B. Devière J. Foley T.R. Haber G.B. Peters J.H. Lehman G.A. Endoscopic implantation of Enteryx for treatment of GERD 12-month results of a prospective, multicenter trial.Am J Gastroenterol. 2003; 98: 1921-1930Crossref PubMed Scopus (131) Google Scholar, 12Schumacher B, Neuhaus H, Ortner M, Laugier R, Benson M, Boyer J, Ponchon T, Hagenmüller F, Grimaud J-C, Rampal P, Rey J-F, Fuchs K-H, Allgaier H-P, Hochberger J, Stein HJ, Armengol JAR, Siersema PD, Devière J. Reduced medication dependency and improved symptoms and quality of life 12 months after Enteryx implantation for gastroesophageal reflux. J Clin Gastroenterol (in press).Google Scholar A preliminary report has indicated continued benefit of the procedure through 24 months of follow-up.13Cohen L.B. Johnson D.A. Ganz R. Aisenberg J. Devière J. Lehman G. Enteryx solution, a minimally invasive injectable treatment for GERD analysis of extended follow-up through 24 months.Am J Gastroenterol. 2003; 98 (abstr): A71Google ScholarThus far unknown is the extent to which the observed benefits may reflect a placebo response. In a meta-analysis of 22 drug trials in patients with erosive/ulcerative esophagitis, 12% of patients receiving placebo had complete disappearance of symptoms compared with 32% of active drug recipients.14Pace F. Maconi G. Molteni P. Minguzzi M. Bianchi Porro G. Meta-analysis of the effect of placebo on the outcome of medically treated reflux esophagitis.Scand J Gastroenterol. 1995; 30: 101-105Crossref PubMed Scopus (22) Google Scholar The proportion of heartburn-free days in the placebo group was 36%–46% as contrasted with 63%–66% of patients receiving 40 mg esomeprazole in 2 randomized, double-blind, multicenter trials.15Katz P.O. Castell D.O. Levine D. Esomeprazole resolves chronic heartburn in patients without erosive oesophagitis.Aliment Pharmacol Ther. 2003; 18: 875-882Crossref PubMed Scopus (48) Google Scholar In a sham-controlled trial of endoluminal radiofrequency energy treatment for GERD, 33% of the sham-treated patients were free of heartburn symptoms versus 61% of the active radiofrequency energy treatment group.16Corley D.A. Katz P. Wo J.M. Stefan A. Patti M. Rothstein R. Edmundowicz S. Kline M. Mason R. Wolfe M.M. Improvement of gastroesophageal reflux symptoms after radiofrequency energy a randomized, sham-controlled trial.Gastroenterology. 2003; 125: 668-676Abstract Full Text Full Text PDF PubMed Scopus (286) Google Scholar There is also the possibility that benefit may be overestimated in noncontrolled trials. The results of a randomized trial comparing Enteryx implantation with a sham procedure are described in this report.Patients and methodsStudy designThis multicenter, parallel-group, patient-blinded, randomized, controlled trial was conducted at 4 centers, 2 in Germany and one each in Belgium and Italy, under ethics committee approval from each center (Figure 1). Patients who had rendered their written informed consent were randomly allocated to Enteryx implantation or a sham procedure by means of a set of individually sealed opaque envelopes prepared at a centralized location. Randomized group assignments were generated by computer with a target ratio of 1:1. Patients were not apprised of their group assignments. They were informed that a second treatment would be offered after the 3-month follow-up visit if their symptoms continued. Patient recruitment commenced in November 2001, and follow-up data were collected through August 2004.End pointsThe primary study end point was ≥50% reduction in PPI use compared with baseline. Secondary end points included ≥50% improvement in GERD health-related quality of life (HRQL) heartburn score17Velanovich V. Vallance S.R. Gusz J.R. Tapia F.V. Harkabus M.A. Quality of life scale for gastroesophageal reflux disease.J Am Coll Surg. 1996; 183: 217-224PubMed Google Scholar and the proportion of patients not undergoing a subsequent Enteryx procedure. Trial sample size was selected to attain 80% power in demonstrating a difference in response rate with respect to the primary end point based on the assumption of a 65% response rate in the Enteryx group and a 15% rate in the sham group.EligibilityNonpregnant patients 18 years of age or older with a history of heartburn, regurgitation, or both and American Society of Anesthesiologists Physical Status Classification I or II were eligible. Patients must also have demonstrated a satisfactory symptomatic response (GERD-HRQL heartburn score ≤11) to a previous course of PPI therapy ≥3 months. On PPI withdrawal for a minimum of 10 days, candidates must have experienced symptomatic relapse (GERD-HRQL heartburn score ≥20) and exhibited excessive lower esophageal acid exposure during prolonged pH-metry >12 hours (pH ≤ 4 for ≥5% of total or ≥3% of supine time). Exclusion criteria included the following: non-GERD esophageal motility disorders; diabetic gastroparesis; significant multisystem disease; prior gastric, esophageal, or GERD surgery; scleroderma, dermatomyositis, calcinosis-Raynaud’s-esophagus-sclerodactyly syndrome, Sjögren’s syndrome, or Sharp’s syndrome; persistent esophagitis greater than or equal to grade III (Savary-Miller); Barrett’s epithelium; hiatus hernia ≥5 cm; body mass index ≥35 kg/m2; autoimmune disorder requiring therapy in the preceding 2 years; suspected or confirmed esophageal or gastric cancer; esophageal or gastric varices; and anticoagulant use other than 300 mg aspirin or equivalent per day.Data collectionPatient history was elicited at the screening visit, after which patients maintained a diary throughout the trial documenting their use of PPIs. GERD-HRQL and 36-item Short-Form Health Survey (SF-36)18Ware Jr, J.E. Sherbourne C.D. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection.Med Care. 1992; 30: 473-483Crossref PubMed Scopus (27626) Google Scholar questionnaires were completed at all visits (Figure 1). In order to exclude patients with motility disorders, dual manometry/pH-metry was performed at the baseline evaluation while patients were off PPI therapy. Prolonged pH-metry (>12 hours) and barium esophagrams were part of the evaluation at baseline while patients were off PPI therapy; prolonged pH-metry was repeated at 6 months, while a barium esophagram was optional at this time point. Chest radiographs were obtained at the 3- and 6-month visits. The percentage of residual Enteryx implant material during follow-up as compared with the day of implantation was estimated by the investigators from radiograph images. Upper gastrointestinal endoscopy could be performed as an option at 6 months. A final follow-up evaluation will be conducted at 12 months.Study procedurePPI therapy was resumed ≥3 days before the study procedure. After an overnight fast, conscious sedation with midazolam or deep sedation with propofol was administered according to the standard practices of the study centers for upper gastrointestinal endoscopy. All patients received 1 mg glucagon and prophylactic antibiotics. Enteryx, which consists of ethylene vinyl alcohol in dimethyl sulfoxide with added radiopaque micronized tantalum powder, was injected either within the muscle layer or into the deep submucosal layer of the distal esophagus and cardia under both fluoroscopic and endoscopic guidance by methods previously described.3Johnson D.A. Ganz R. Aisenberg J. Cohen L.B. Devière J. Foley T.R. Haber G.B. Peters J.H. Lehman G.A. Endoscopic implantation of Enteryx for treatment of GERD 12-month results of a prospective, multicenter trial.Am J Gastroenterol. 2003; 98: 1921-1930Crossref PubMed Scopus (131) Google Scholar Introduced through the working channel of the endoscope, a 4-mm long, 23-gauge sclerotherapy-type needle was used to inject in an antegrade direction at or just below the squamocolumnar junction (Z-line). The target total volume of Enteryx injected was 6–8 mL.The sham group underwent upper gastrointestinal endoscopy only, either with deep propofol-induced sedation or midazolam sedation for a minimum of 15 minutes. For those patients in the sham group receiving midazolam only, attending physicians and staff performed the same procedures used for Enteryx implantation except the actual injection of the copolymer solution. Patients received a 10-day supply of PPI medication and were instructed to discontinue their use of PPIs 10 days following the procedure. Thereafter, they were prescribed PPIs only if necessary and were asked to take only the minimum dosage required to alleviate their symptoms and to record such PPI use.Re-treatmentBoth groups had undergone an Enteryx or sham “treatment” and were eligible for re-treatment if symptom control was unsatisfactory (GERD-HRQL heartburn score >15) at the 3-month visit. Enteryx implantation was the only form of re-treatment offered. Eligible patients were notified of their group assignment so that they could make an informed decision on proceeding with re-treatment, which could be scheduled after the 3-month visit. Before re-treatment, patients who had resumed PPI therapy were required to discontinue this therapy for at least 10 days and complete GERD-HRQL questionnaires.Statistical analysisBinary study end points were analyzed by calculation of rate ratios and exact confidence intervals (CIs) around the rate ratios. The rate ratio was defined as the proportion of total patients in the Enteryx group with the outcome of interest (eg, ≥50% reduction in PPI use) divided by the corresponding proportion in the sham group. A rate ratio of 1 indicates no between-group difference. When the rate ratio differs from 1 and the CI does not contain 1, a significant effect of group assignment can be inferred. Within-group changes in binary outcomes were assessed by exact McNemar test. Exact Clopper-Pearson CIs were calculated for binary proportions. Outcome predictors were evaluated by exact logistic regression.Differences in continuous variables were determined by t test in the case of normally distributed data and by exact Mann-Whitney or Wilcoxon test otherwise. Median within-group changes versus baseline off PPIs were obtained by exact Hodges-Lehmann estimation. Absence of zero from the CI for the difference indicates statistical significance. Baseline PPI use was assessed by exact Wilcoxon-Mann-Whitney test for 2 ordered multinomials.ResultsTwenty-three of the 64 study patients (36%) were enrolled at the Hôpital Erasme (Brussels, Belgium), 16 (25%) at the Policlinico Agostino Gemelli (Rome, Italy), 13 (20%) at the Evangelisches Krankenhaus Düsseldorf (Düsseldorf, Germany), and 12 (19%) at the Universitätsklinikum Charité (Berlin, Germany). Two patients in the sham group and one in the Enteryx group requested to be discontinued from the trial after the 3-month visit (Figure 2). There were no statistically significant between-group differences in baseline patient data (Table 1). In deviation from the protocol, 4 patients entered the trial despite GERD-HRQL heartburn scores >11 at the screening evaluation on PPIs and 5 additional patients entered the trial despite heartburn scores 15), of whom 6 (67%) actually underwent re-treatment (Figure 2). In the sham group, 20 of 23 eligible patients (87%) proceeded to Enteryx implantation as re-treatment. In deviation from the study protocol, 6 additional patients in the sham group underwent re-treatment despite failure to fulfill the heartburn score eligibility requirement. The rate of eligibility for re-treatment was lower in the Enteryx group than in the sham group (rate ratio, 0.42; CI, 0.22–0.73).Significantly more Enteryx-treated (81%) than sham-treated (19%) patients did not undergo re-treatment (Figure 3). With exclusion of the 6 patients in the sham group who underwent re-treatment despite ineligibility, the proportion of the Enteryx group not proceeding to re-treatment remained higher than that of the sham group (rate ratio, 3.52; CI, 1.80–8.59; P < .001). The time elapsed between the original procedure and the re-treatment procedure averaged 136 ± 38 days for the Enteryx group and 120 ± 24 days for the sham group (P = .20).Outcomes at 6 monthsIn the Enteryx group, PPI use and symptoms remained stable at 6 months (Figure 4). Because 26 of the 32 patients in the sham group (81%) had undergone an Enteryx re-treatment procedure after 3 months, the major between-group differences observed at 3 months no longer persisted at 6 months.Figure 4Percentages of patients with (A) PPI use reduction ≥50%, (B) complete cessation of PPI use, and GERD-HRQL (C) heartburn and (D) regurgitation score improvement ≥50%. The majority of patients in the sham group (26 of 32) underwent an Enteryx procedure between the 3- and 6-month evaluations, so that between-group differences were no longer apparent at 6 months. For the 2 PPI use end points, all patients except 1 in the Enteryx group were evaluable at 3 months and all but 1 in the sham group at 6 months. For the 2 symptom end points, all patients except 2 in the Enteryx group were evaluable at 3 months. At 6 months, all but 3 patients in the Enteryx group and 6 patients in the sham group were evaluable with respect to heartburn score and all except 2 and 5 patients, respectively, with regard to regurgitation score. Depicted data are without exclusion of the 6 re-treated patients in the Enteryx group and 6 non-re-treated patients in the sham group. Error bars show exact CI. Indicated P values are for the significance of within-group change from 3 to 6 months by exact McNemar test. Median symptom scores at baseline off PPI therapy appear in Table 1.View Large Image Figure ViewerDownload (PPT)Median heartburn score improvement at 6 months versus baseline off PPIs in the Enteryx group (63%; CI, 50%–75%) was unchanged from that at 3 months. By contrast, in the sham group, heartburn score improvement at 6 months (70%; CI, 52%–82%) was markedly higher than at 3 months due to the crossover of most patients in this group to Enteryx implantation. With exclusion of the 6 patients in the sham group who underwent re-treatment despite ineligibility, heartburn score for the sham group improved by a median of 71% (CI, 52%–82%) at 6 months.At 6 months, significant median SF-36 physical and mental score improvements of 18% (CI, 5%–31%) and 12% (CI, 3%–22%), respectively, persisted in the Enteryx group. The sham group, which exhibited no significant improvements at 3 months, experienced significant median improvements at 6 months in SF-36 physical score of 22% (CI, 12%–33%) and mental score of 8% (CI, 0.1%–22%).The PPI use and heartburn results at 6 months were not substantially affected by the contribution of 6 re-treated patients in the Enteryx group and 6 non-re-treated patients in the sham group. Thus, with these 12 patients excluded, reduction in PPI use ≥50% was attained at 6 months by 85% (CI, 65%–96%) of the Enteryx group and 77% (CI, 56%–91%) of the sham group, complete cessation of PPI use by 69% of the Enteryx group (CI, 48%–86%) and 62% (CI, 41%–80%) of the sham group, and heartburn score improvement ≥50% by 61% of the Enteryx group (CI, 39%–80%) and 73% (CI, 50%–89%) of the sham group. Corresponding values without the exclusions were 84% of the Enteryx group (CI, 67%–95%) and 71% (CI, 52%–86%) of the sham group for reduction in PPI use ≥50%, 66% of the Enteryx group (CI, 47%–81%) and 58% (CI, 39%–75%) of the sham group for complete cessation of PPI use, and 66% (CI, 46%–82%) of the Enteryx group and 73% (CI, 52%–88%) of the sham group for heartburn score improvement ≥50%.For the 6 re-treated patients in the Enteryx group, the rate of PPI use reduction ≥50% at 6 months was 83% (CI, 36%–100%) compared with 50% (CI, 12%–88%) at 3 months. Thus, although this was a small patient subgroup, the results were suggestive of incremental benefit resulting from the repeat Enteryx procedure.pH-metryProlonged pH-metry was not consistently performed at the same follow-up visit, and in some patients this diagnostic monitoring procedure was performed at more than one follow-up evaluation. In Table 2, the baseline percent total time at pH ≤ 4 is compared with results from the final pH-metry in the 39 patients with available data. There were no statistically significant between-group differences in esophageal acid exposure. Because of the incompleteness of the data and varied times of collection, the impact on pH in this study remains indeterminate. A correlation was not apparent between change in total time at pH ≤ 4 and either residual implant volume (P = .19) or change in heartburn score (P = .61).Table 2pH-metryGroupn% Total time at pH < 4PBaselineFinalMedianIQRMedianIQRSham1614.07.1–22.812.77.0–21.3.85Enteryx2313.37.3–20.811.24.1–24.3.94Pooled3913.37.2–22.411.26.6–22.8.87IQR, interquartile range. Open table in a new tab Residual implantAt 3 months, after either an original implantation in the Enteryx group or a re-treatment procedure in either group, the mean estimated residual implant volume was 67% (CI, 54%–79%). This finding remained essentially unchanged at 6 months (66%; CI, 56%–76%).No residual implant could be detected in 2 patients in the Enteryx group. Both patients were completely off PPI therapy at 6 months. Neither had been re-treated.Outcome predictorsPotential outcome predictors were screened in an exact multivariate logistic regression model with randomized group assignment as a covariate. No significant relationship could be detected between PPI dose reduction ≥50% at 3 mont
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