Clinical Literature

The following is a sampling of published clinical data and abstracts on the Plicator® procedure. To request a copy of a specific paper, please send an email request to info@ndosurgical.com.

Endoscopic Full-Thickness Plication for the Treatment of GERD: A Randomized, Sham-Controlled Trial

Endoscopic Full-Thickness Plication for the Treatment of GERD: Long-Term Multicenter Results

The Plicator™ Procedure for the Treatment of GERD: 12-month Multicenter Results

Endoscopic Full-Thickness Plication for the Treatment of GERD: 12-month Follow-Up for the North American Open-Label Trial

Objective Improvements Following Full-Thickness Gastric Cardia Plication for Complicated GERD

Endoluminal GERD Treatments: Critical Appraisal of Current Literature with Evidenced-Based Medicine Instruments

Endoscopic Full-Thickness Plication for the Treatment of GERD: A Randomized, Sham-Controlled Trial

Richard Rothstein, Dartmouth Hitchcock Medical Center Charles Filipi, Creighton University Medical Center, Karel Caca, University of Leipzig, Ronald Pruitt, Nashville Gastrointestinal Specialists, Klaus Mergener, Digestive Health Specialists, Alfonso Torquati, Vanderbilt University, Gregory Haber, Lenox Hill Hospital, Yang Chen, University of Colorado Health Sciences Center, Kenneth Chang, University of California at Irvine Medical Center, David Wong, Tri Valley Gastroenterology, Jacques Deviere, Erasme Hospital, Douglas Pleskow, Beth Israel Deaconess Medical Center, Charles Lightdale, Columbia University Medical Center, Alain Ades, Seacoast Gastroenterology, Richard Kozarek, Virginia Mason Medical Center, Anthony Lembo, Beth Israel Deaconess Medical Center

Aim: To determine the effectiveness of endoscopic full-thickness plication for the treatment of GERD in comparison to a sham procedure.

Methods: Patients with symptomatic GERD requiring maintenance proton pump inhibitor therapy were entered into a randomized, single-blind, prospective, multicenter trial. Seventy-eight patients were randomly assigned to undergo endoscopic full-thickness restructuring of the gastric cardia with transmural suture. Eighty-one patients underwent a sham procedure. Group assignments were revealed following the 3-month evaluation. The primary endpoint was ≥ 50% improvement in GERD-HRQL score. Secondary endpoints included medication use and esophageal acid exposure.

Results: At 3-months, the proportion of patients achieving ≥ 50% improvement in GERD-HRQL score was significantly greater in the active group (65%) compared to the sham group (20%), (p<0.001). Complete PPI cessation was higher among patients in the active group than in the sham group (57% vs. 25%, p<0.001). Median % time pH<4 was significantly reduced in the active group (10 vs. 7, p<0.001), but not in the sham group (10 vs. 10, p=0.309). Between-group analysis revealed the active therapy to be superior the sham in improving median % time pH<4 (p=0.008). Analysis by intention-to-treat for primary and secondary endpoints remained significant. Preliminary interim analysis of the 6-month data demonstrates that patients in the treatment group continue to have a sustained response in PPI cessation and GERD-HRQL scores There were no perforations or deaths.

Conclusions: Endoscopic full-thickness plication more effectively reduces GERD symptoms, PPI use, and esophageal acid exposure than a sham procedure. The effects appear durable, and need to be studied in longer-term follow-up. Gastroenterology 2006; 131: 704 – 712.

Endoscopic Full-Thickness Plication for the Treatment of GERD: Long-Term Multicenter Results

Douglas Pleskow, Beth Israel Deaconess Medical Center, Richard Rothstein, Dartmouth Hitchcock Medical Center, Richard Kozarek, Virginia Mason Medical Center, Gregory Haber, Lenox Hill Hospital, Christopher Gostout, Mayo Clinic, Anthony Lembo, Beth Israel Deaconess Medical Center

Background: The Plicator (NDO Surgical, Inc., Mansfield, MA) delivers a transmural suture through the gastric cardia to restructure the anti-reflux barrier. Published reports have shown the Plicator procedure to be effective in reducing GERD symptoms and medication use at 1-year post-plication.

Aim: To assess the long-term safety and efficacy of endoscopic full-thickness plication for the treatment of symptomatic GERD.

Methods: In a prospective multicenter trial, 64 patients with chronic heartburn requiring maintenance daily anti-secretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1cm below the GE junction. Re-treatments were not permitted. Patients were evaluated at baseline and 12-months for GERD symptoms and medication use. Long-term subject follow-up was completed under a study extension to evaluate safety, efficacy and durability of the procedure in a subset of the original cohort.

Results: Twenty-nine patients completed the long-term follow-up (median follow-up interval: 36.4 months, range: 31.2-43.9). All procedure-related adverse events occurred acutely, as previously reported, and no new adverse events were observed during extended follow-up. At 36-months post-procedure, 61% (17/28) of baseline PPI dependent patients remained off daily PPI therapy. Treatment effect remained stable from the 12- to 36-month follow-up intervals, with 21/29 patients off daily PPI at 12 months compared to 18/29 patients at 36-months. Median GERD-HRQL scores remained significantly improved at 36-months versus baseline off-meds scores (8 vs. 19, p<0.001). In addition, the proportion of patients achieving ≥ 50% improvement in GERD-HRQL score was consistent from 12-months (59%) to 36-months (55%).

Conclusions: Endoscopic full-thickness plication can effectively reduce GERD symptoms and medication use for at least 3-years post-procedure. Treatment effect is stable from 1 to 3-years and there are no long-term procedural adverse effects. Surgical Endoscopy 2007; 21: 439-444.

The Plicator™ Procedure for the Treatment of GERD: 12-month Multicenter Results

Gregory Haber, Lenox Hill Hospital, Paulo Sakai, Eduardo Moura, Fauze Maluf-Filho, Hospital das Clinicas Robert Enns, St. Paul’s Hospital, Douglas Pleskow, Anthony Lembo, Beth Israel Deaconess Medical Center

Background: The Plicator (NDO Surgical Inc., Mansfield, MA) is a unique endoscopic suturing device which delivers a transmural suture. The ability to achieve serosal tissue apposition allows for restructuring of the cardia and reshaping of the valvular mechanism at the gastro-esophageal junction (GEJ).

Aim: To assess the safety and 12-month efficacy of endoscopic full-thickness suturing using a second generation, reduced diameter Plicator.

Methods: Thirty-six patients with chronic heartburn requiring maintenance anti-secretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1cm below the GEJ. Study exclusions included hiatal hernia >2cm, Grades III and IV esophagitis, and Barrett’s esophagus. At baseline and 12-months post-plication, patients were evaluated for GERD symptoms and medication use. Ambulatory 24-hr pH studies were conducted at baseline and repeated between 6 and 12-months post-plication.

Results: Thirty-six patients underwent endoscopic full-thickness plication with two patients lost to follow-up. There were no serious adverse events. Common side effects included sore throat (23%) and epigastric pain (21%) which resolved spontaneously. Two patients were admitted overnight for observation. One year post-plication, 68% (23/34) of PPI dependent patients remained off daily PPI therapy; with an additional 12% (4/34) able to reduce their PPI dose by at least 50%. Median GERD-HRQL scores were improved versus baseline off-meds (16.0 vs. 7.0) and were comparable to baseline on-meds values (7.0 vs. 5.0). Twenty-six subjects underwent post-procedure ambulatory pH studies (mean follow-up 9.5 months). Of these, 73% demonstrated an improvement in distal esophageal acid exposure. Median % time pH<4 decreased 29% (9.9 to 8.1) with 23% of patients experiencing pH normalization.

Conclusions: Endoscopic full-thickness suturing with the reduced diameter Plicator was found to be a safe procedure that can effectively reduce symptoms, medication use and esophageal acid exposure associated with GERD. Gastrointest Endosc 2005; 61: 5, AB17.

Endoscopic Full-Thickness Plication for the Treatment of GERD: 12-month Follow-Up for the North American Open-Label Trial

Douglas Pleskow, Beth Israel Deaconess Medical Center, Richard Rothstein, Dartmouth Hitchcock Medical Center, Simon Lo, Cedars Sinai Medical Center, Robert Hawes, Medical University of South Carolina, Richard Kozarek, Virginia Mason Medical Center, Gregory Haber, St. Michael's Hospital, Christopher Gostout, Mayo Clinic, Anthony Lembo, Beth Israel Deaconess Medical Center

Background: The aim of this study was to assess the intermediate-term (12-month) safety and efficacy of endoscopic full-thickness plication in patients with symptomatic GERD.

Methods: Sixty-four patients with chronic heartburn that required maintenance anti-secretory therapy received a single, endoscopically placed, full-thickness plication in the gastric cardia 1 cm distal to the gastroesophageal junction. At baseline and 12 months after plication, patients completed the GERD Health Related Quality of Life questionnaire, Gastrointestinal Symptom Rating Scale, and SF-36 Health Survey, as well as a medication use diary. Ambulatory 24-hour pH monitoring and esophageal manometry were obtained at baseline and 3 months after plication. At 6 months after plication, the 24-hour pH study was repeated.

Results: Of the 57 patients who completed the 12-month follow-up, 40 (70%) were no longer taking a proton pump inhibitor. Median GERD Health Related Quality of Life scores were improved compared with baseline while taking medication (19.0 vs. 5.0; p < 0.0001) and while not taking medication (13.0 vs. 5.0; p < 0.002). At 6 months after the procedure, an improvement in distal esophageal acid exposure was demonstrated in 40 of 51 patients (80%), with a decrease of 39% in the median percentage of time the pH was less than 4 (p < 0.0001). Normal pH scores were observed in 30% of patients. All procedure-related adverse events occurred acutely, as previously reported, and no new adverse event was observed during extended follow-up.

Conclusions: Full-thickness plication at the gastroesophageal junction is an effective endoscopic procedure for treatment of patients with symptoms caused by GERD. It reduces reflux symptoms and anti secretory medication use over at least a 1-year period. Gastrointest Endosc 2005; 61: 6, 643-9.

Objective Improvements Following Full-Thickness Gastric Cardia Plication for Complicated GERD

Edward Lin, C. Daniel Smith, Emory University School of Medicine, Shahriar Sedghi, Mercer University School of Medicine

Background: Single full-thickness (transmural) plication of the proximal gastric cardia performed endoscopically has been proposed as a method of creating an intraluminal barrier against gastric reflux into the esophagus. We report 10 patients with complicated GERD (3 with BMI > 50 and high dose medication requirements; 2 with hiatal hernia >2cm; 3 failed prior anti-reflux surgery; 2 failed endoscopic mucosal suturing) who have undergone treatment with the Plicator device (NDO Surgical, Mansfield, Mass).

Methods: Prior to the procedure, all patients had objective testing (pH, endoscopy, contrast esophagrams, motility studies). Clinical outcomes were monitored for anti-secretory medication use and symptom scores. Eight patients had objective post-procedure evaluations in the first 2 months after the procedure. Video documentation ensured consistent procedure application.

Results: Symptom scores improved for chest pain, heartburn, regurgitation, voice symptoms and cough in all patients. Complete symptom resolution in at least one category was observed in 70%. The reduction in medication use was reported in 80%, with 50% of the patients discontinuing medications completely. Amelioration of reflux was demonstrated in 6 of 8 contrast esophagrams, and 4 of 5 pH studies (3 completely normalized). All procedures were performed in the outpatient setting. There were no complications.

Conclusions: Endoscopic full-thickness plication of the gastric cardia may offer surgeons another alternative for treating selected patients with complicated GERD. This is also the first report of employing endoscopic plication in patients who failed anti-reflux surgery with favorable early objective outcomes. SAGES 2005; Abstract S040.

Endoluminal GERD Treatments: Critical Appraisal of Current Literature with Evidenced-Based Medicine Instruments

Alfonso Torquati, William O. Richards, Department of Surgery, Vanderbilt University School of Medicine

Background: The literature of endoluminal treatment of gastroesophageal reflux disease (GERD) widely varies in the level of evidence presented for analysis. Therefore there is a need for a comprehensive evidenced-based medicine (EBM) analysis of the current literature evidence of the three FDA-approved modalities used for endoluminal treatment of GERD.

Search Strategy: In January 2007, the MEDLINE database was searched for randomized control trials (RCTs), and controlled clinical trials of currently available endoluminal treatment of GERD. Database searches combined the specific endoluminal device keywords with the condition- specific keyword (e.g., GERD).

Data Collection and Analysis: All relevant studies have been categorized according to the evidence they provide according to the guidelines for Levels of Evidence and Grades of Recommendation supplied by the Oxford Centre for Evidence-Based Medicine.

Main Results and Authors Conclusions: Sixteen studies met the inclusion criteria, representing 787 patients. The methodological quality of most of the included studies was average; four studies were grade 1b (individual randomized trial), 10 were grade 2b (individual cohort study), and two were grade 3b (individual case-control study). There is grade 1b and 2b evidence demonstrating the EndoCinch plication is effective in reducing GERD symptoms at short-term follow up. However, in the majority of the studies analyzed, the procedure does not significantly reduce the acid exposure in the distal esophagus. The majority of studies with long-term outcome showed disappointing outcomes, probably due to suture loss in the majority of patients. There is grade 1b and 2b evidence demonstrating that the Stretta procedure is effective in reducing GERD symptoms at short- and mid-term follow up. However, in the majority of the studies analyzed, the procedure did not reduce significantly the acid exposure in the distal esophagus. There is grade 1b and 2b evidence demonstrating that full-thickness plication is effective in reducing GERD symptoms, and acid exposure in the distal esophagus. Surgical Endoscopy, 2007, Vol. 21, pp.697-706.