A Study to Determine the Effectiveness of Endoscopic Full-Thickness Plication for the Treatment of GERD

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

The aim of this study was to determine the effectiveness of endoscopic full-thickness plication (Plicator; NDO Surgical, Inc., Mansfield, MA) for the treatment of GERD in comparison to a sham procedure.

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.

Patients achieving ≥ 50% improvement in GERD-HRQL score at 3-months versus baseline off-meds were considered responsive to their assigned procedure. Patients who failed to reach this level of improvement at 3-months were considered non-responders. Analysis of these dichotomized variables (responder/non-responder) was done using Fisher's exact test comparing the proportion of responders between the active and sham groups. Intent-to-treat analysis was also performed. The null hypothesis was that the proportion of responders was the same in both the active and sham groups. Testing was done at the 5% level of significance (alpha=0.05).

Study Overview

• Status: Terminated
• Conditions: Gastroesophageal Reflux Disease (GERD)
• Intervention / Treatment: Device: NDO Full-thickness Plicator; Device: Sham Control

• Study Type: Interventional
• Enrollment (Actual): 159
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Erasme Hospital
• Germany
  • Heidelberg, Germany, 71640
    • Klinikum Ludwigsburg, University of Heidelburg
• United States
  • California
    • Orange, California, United States, 92868
      • University of California at Irvine Medical Center
    • San Ramon, California, United States, 94583
      • Tri Valley Gastroenterology
  • Colorado
    • Denver, Colorado, United States, 80010
      • University of Colorado Health Science Center
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Beth Israel Deaconess Medical Center
  • Nebraska
    • Omaha, Nebraska, United States, 68131
      • Creighton University Medical Center
  • New Hampshire
    • Exeter, New Hampshire, United States, 03833
      • Seacoast Gastroenterology
    • Lebanon, New Hampshire, United States, 03756
      • Dartmouth Hitchcock Medical Center
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
    • New York, New York, United States, 10021
      • Lenox Hill Hospital
  • Tennessee
    • Nashville, Tennessee, United States, 37240
      • Vanderbilt University Medical Center
    • Nashville, Tennessee, United States, 37205
      • Nashville Medical Research and the Maria Nathanson Center of Excellence
  • Washington
    • Seattle, Washington, United States, 98101
      • Virginia Mason Medical Center
    • Tacoma, Washington, United States, 98405
      • Digestive Health Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Patients 18 years or older with a history of heartburn or regurgitation symptoms requiring daily PPI therapy were recruited.

Inclusion Criteria:

• GERD-HRQL score ≥ 15 while off PPI therapy, and at least 6 points higher than on-PPI score
• Pathologic esophageal acid exposure, defined as pH<4.0 ≥ 4.5% of a 24- or 48-hour monitoring period or a DeMeester score > 14.7
• Lower esophageal resting pressure of at least 5mmHg; and
• Suitability for surgery (American Society of Anesthesiologists Physical Status Classification I or II).

Exclusion Criteria:

• Significant esophageal dysmotility as determined by manometry
• Esophagitis grade III or IV (Savary-Miller)
• Barrett's epithelium
• Hiatus hernia > 2cm
• Persistent dysphagia, weight loss, esophageal bleeding, vomiting, gas or bloating
• Esophageal or gastric varices
• Previous endoscopic or surgical anti-reflux procedure
• Other esophageal or gastric surgery
• Chronic use of anticoagulant or platelet anti-aggregation therapy (other than for cardiac prophylaxis); and
• Pregnancy.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1; NDO Endoscopic Full-thickness Plicator procedure	Device: NDO Full-thickness Plicator; A low-profile (≤6mm) gastroscope was advanced and an EGD followed by Savary wire placement was performed. The gastroscope was then removed and the Plicator was advanced directly over the wire and into the stomach. The gastroscope was re-introduced through the Plicator, and the Plicator was retroflexed under direct endoscopic visualization to the anterior gastric cardia, approximately 1cm below the gastroesophageal (GE) junction. The Plicator arms were opened and the endoscopic tissue retractor was advanced deeply into the gastric cardia. The gastric wall was then retracted into the open arms of the Plicator. The arms were closed and a single, transmural pledgeted suture was deployed. The Plicator and gastroscope were then removed and the gastroscope re-inserted to evaluate the post-plication GE junction.; Other Names: Active Plicator procedure
Sham Comparator: 2; Sham control procedure	Device: Sham Control; The sham procedure was identical to the treatment procedure through the positioning of the retroflexed Plicator 1cm below the GE junction. The Plicator instrument remained in this position for 15 minutes, based on average procedure times established in previous studies. During the sham procedure, physician investigators were required to talk through the procedure steps to maintain the patient blind.; Other Names: Sham control procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
>/=50% improvement in GERD-Health Related Quality of Life Score	3-months post-procedure

Secondary Outcome Measures

Outcome Measure	Time Frame
GERD medication use	3-months post-procedure
Esophageal acid exposure	3-months post-procedure
Heartburn score as measure by visual analog scale	3-months post-procedure
Quality of Life as measure by SF-36	3-months post-procedure

Collaborators and Investigators

• Sponsor: NDO Surgical, Inc.
• Investigators: Principal Investigator: Douglas Pleskow, MD, Beth Israel Deaconess Medical Center, Boston MA; Principal Investigator: Richard Kozarek, MD, Virginia Mason Medical Center, Seattle, WA; Principal Investigator: Richard Rothstein, MD, Dartmouth-Hitchcock Medical Center, Lebanon, NH; Principal Investigator: Charles Filipi, MD, Creighton University Medical Center, Omaha, NE; Principal Investigator: Karel Caca, MD, Klinikum Ludwigsburg, University of Heidelburg, Heidelburg, Germany; Principal Investigator: Ronald Pruitt, MD, Nashville Medical Research and the Maria Nathanson Center of Excellence, Nashville, TN; Principal Investigator: Klaus Mergener, MD, Digestive Health Specialists, Tacoma, WA; Principal Investigator: Alfonso Torquati, MD, Vanderbilt University Medical Center, Nashville, TN; Principal Investigator: Gregory Haber, MD, Lenox Hill Hospital, New York, NY; Principal Investigator: Yang Chen, MD, University of Colorado Health Science Center, Denver, CO; Principal Investigator: Kenneth Chang, MD, University of California at Irvine Medical Center, Orange, CA; Principal Investigator: David Wong, MD, Tri Valley Gastroenterology, San Ramon, CA; Principal Investigator: Jacques Deviere, MD, Erasme Hospital, Brussels, Belgium; Principal Investigator: Charles Lightdale, MD, Columbia University Medical Center, New York, NY; Principal Investigator: Alain Ades, MD, Seacoast Gastroenterology, Exeter, NH

Publications and helpful links

General Publications

• Rothstein R, Filipi C, Caca K, Pruitt R, Mergener K, Torquati A, Haber G, Chen Y, Chang K, Wong D, Deviere J, Pleskow D, Lightdale C, Ades A, Kozarek R, Richards W, Lembo A. Endoscopic full-thickness plication for the treatment of gastroesophageal reflux disease: A randomized, sham-controlled trial. Gastroenterology. 2006 Sep;131(3):704-12. doi: 10.1053/j.gastro.2006.07.004.

Study record dates

Study Major Dates

• Study Start: January 1, 2005
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: December 14, 2007
• First Submitted That Met QC Criteria: December 17, 2007
• First Posted (Estimate): December 18, 2007

Study Record Updates

• Last Update Posted (Estimate): July 16, 2008
• Last Update Submitted That Met QC Criteria: July 15, 2008
• Last Verified: May 1, 2008

More Information

Terms related to this study

• Keywords: GERD; Sham; Randomized Controlled Study; Endoscopic Full-thickness Plication; Plicator
• Additional Relevant MeSH Terms: Digestive System Diseases; Gastrointestinal Diseases; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastroesophageal Reflux
• Other Study ID Numbers: 135-01885