LINX Reflux Management System Clinical Study Protocol

Tracking Information
First Submitted Date ICMJE	October 20, 2008
First Posted Date ICMJE	October 22, 2008
Results First Submitted Date	April 25, 2012
Results First Posted Date	November 13, 2013
Last Update Posted Date	May 4, 2018
Study Start Date ICMJE	November 2008
Actual Primary Completion Date	December 2010 (Final data collection date for primary outcome measure)
Current Primary Outcome Measures ICMJE; (submitted: September 9, 2013)	Rate of Occurrence for Device and Procedure Related Serious Adverse Events (SAEs). [ Time Frame: through 24 months ]SAE was defined as any untoward medical occurrence, whether related to the study device or procedure or not, that meets one or more of the following criteria: Results in death Is life-threatening Requires subject hospitalization > 24 hours Requires prolongation of an existing hospitalization Results in persistent or significant disability/incapacity Results in fetal distress, fetal death, or a congenital anomaly or birth defect Requires intervention to prevent permanent impairment or damage. Outcome measure reports number of subjects with reported events.; Normalization of Esophageal Acid Exposure Time or Reduced Total Acid Exposure Time of at Least 50% Compared to the Subject's Baseline Measurement by Esophageal pH Testing. [ Time Frame: 12 Months ]The analysis cohort for the primary efficacy analysis was the treated population which includes all implanted subjects and was determined through esophageal pH testing.
Original Primary Outcome Measures ICMJE	Not Provided
Change History	Complete list of historical versions of study NCT00776997 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures ICMJE; (submitted: September 9, 2013)	At Least a 50% Reduction in Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) Total Score Compared to Baseline [ Time Frame: 12 months ]; Average Daily Proton-pump Inhibitor (PPI) Dosage Reduced by at Least 50% Compared to Baseline [ Time Frame: 12 months ]
Original Secondary Outcome Measures ICMJE	Not Provided
Current Other Outcome Measures ICMJE	Not Provided
Original Other Outcome Measures ICMJE	Not Provided
Descriptive Information
Brief Title ICMJE	LINX Reflux Management System Clinical Study Protocol
Official Title ICMJE	LINX Reflux Management System Clinical Study Protocol
Brief Summary	The purpose of the study is to evaluate the safety and effectiveness of the LINX Reflux Management System in the treatment of Gastroesophageal Reflux Disease (GERD).
Detailed Description	At present, the primary alternative for GERD patients with an incomplete symptomatic response to proton-pump inhibitors (PPIs) is laparoscopic Nissen fundoplication. This surgical procedure continues to be the prevalent non-medical treatment option for GERD patients, despite several important limitations. First, it is a very traumatic procedure, requiring portions of the stomach to be dissected and then wrapped around the tubular esophagus, creating permanent anatomic alterations. Secondly, it can create significant side effects, such as gas bloat syndrome, the inability to belch and the inability to vomit. The intent of the LINX System is to allow a surgeon, using existing laparoscopic techniques and instruments, to augment a weak LES and restore the defective barrier at the gastroesophageal junction (GEJ). This defect of the GEJ is the source of abnormal reflux. The LINX device is an expandable string of individual titanium beads with magnetic cores. The device is laparoscopically placed as a ring around the lower esophageal sphincter. The magnetic attraction of the beads augments the esophageal sphincter's ability to resist gastric pressures that cause reflux. At rest, the LINX device encircles the sphincter with each bead resting against an adjacent bead, to avoid compression of the tubular esophagus. When swallowing, higher pressures are created, allowing the magnetic bond between beads to break, and the LINX implant to expand radially. This serves to preserve swallow and other physiologic functions, such as belching and vomiting, and avoids the side effect of post-prandial bloating. The device can be placed with minimal dissection, preserving anatomy, and is also removable, if necessary. This provides important benefits as it preserves the native anatomy, unlike the Nissen procedure.
Study Type ICMJE	Interventional
Study Phase	Not Applicable
Study Design ICMJE	Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
Condition ICMJE	Gastroesophageal Reflux
Intervention ICMJE	Device: Magnetic Sphincter Augmentation; The area of the lower esophageal sphincter (LES) is accessed using a standard laparoscopic approach. The tubular esophagus, in the area of the LES, is sized and the appropriately sized sphincter augmentation device is placed circumferentially around the esophagus in the area of the LES. After confirming proper placement, the ends of the device are secured. At this point, the implant procedure is complete, laparoscopic instruments are withdrawn and access points are closed.; Other Names: LINX Reflux Management System; Magnetic Esophageal Sphincter
Study Arms	Magnetic Sphincter Augmentation; Single-arm study: all subjects were treated with magnetic sphincter augmentation. A subject's baseline measurements prior to sphincter augmentation were compared to post-sphincter augmentation measurements. Subjects served as their own control.; Intervention: Device: Magnetic Sphincter Augmentation
Publications *	Ganz RA, Edmundowicz SA, Taiganides PA, Lipham JC, Smith CD, DeVault KR, Horgan S, Jacobsen G, Luketich JD, Smith CC, Schlack-Haerer SC, Kothari SN, Dunst CM, Watson TJ, Peters J, Oelschlager BK, Perry KA, Melvin S, Bemelman WA, Smout AJ, Dunn D. Long-term Outcomes of Patients Receiving a Magnetic Sphincter Augmentation Device for Gastroesophageal Reflux. Clin Gastroenterol Hepatol. 2016 May;14(5):671-7. doi: 10.1016/j.cgh.2015.05.028. Epub 2015 Jun 2.; Ganz RA, Peters JH, Horgan S, Bemelman WA, Dunst CM, Edmundowicz SA, Lipham JC, Luketich JD, Melvin WS, Oelschlager BK, Schlack-Haerer SC, Smith CD, Smith CC, Dunn D, Taiganides PA. Esophageal sphincter device for gastroesophageal reflux disease. N Engl J Med. 2013 Feb 21;368(8):719-27. doi: 10.1056/NEJMoa1205544.
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status ICMJE	Completed
Actual Enrollment ICMJE; (submitted: April 20, 2012)	100
Original Enrollment ICMJE	Not Provided
Actual Study Completion Date	September 2011
Actual Primary Completion Date	December 2010 (Final data collection date for primary outcome measure)
Eligibility Criteria ICMJE	Inclusion Criteria: Subject must be at least 18 years of age and at least the minimum Age of Majority according to applicable State or Country Law and must be less than 75 years of age, with a life expectancy > 3 years; Subject is a suitable surgical candidate, i.e. is able to undergo general anesthesia and laparoscopic surgery; Documented typical symptoms of gastroesophageal reflux disease (GERD) for longer than 6 months (regurgitation or heartburn which is defined as a burning epigastic or substernal pain which responds to acid neutralization or suppression); Patient requires daily proton pump inhibitor or other anti-reflux drug therapy; Total Distal Ambulatory Esophageal pH must meet the following criteria: pH< 4 for ≥ 4.5% of the time Note: Subjects shall have discontinued any GERD medications for at least 7 days prior to testing.; Subjects with symptomatic improvement on proton-pump inhibitor (PPI) therapy demonstrated by a GERD-Health-Related Quality of Life (GERD-HRQL) score of ≤ 10 on proton-pump inhibitors and ≥ 15 off PPIs, or subjects with a ≥ 6 point improvement when comparing their on PPI and off PPI GERD-HRQL score; GERD symptoms, in absence of PPI therapy (minimum 7 days); If the subject is of child bearing potential must have a negative pregnancy test within one week prior to implant and must agree to use effective means of birth control during the course of the study; Subject is willing and able to cooperate with follow-up examinations; Subject has been informed of the study procedures and the treatment and has signed an informed consent form Exclusion Criteria: The procedure is an emergency procedure; Currently being treated with another investigational drug or investigational device; History of gastroesophageal surgery, anti-reflux procedures, or gastroesophageal/gastric cancer; Any previous endoscopic anti-reflux intervention for GERD; Suspected or confirmed esophageal or gastric cancer; Any size hiatal hernia >3cm as determined by endoscopy; Distal esophageal motility (average of sensors 3 and 4) is less than 35 mmHg peristaltic amplitude on wet swallows or <70% (propulsive) peristaltic sequences; Esophagitis - Grade C or D (LA Classification); Body Mass Index (BMI)>35; Symptoms of dysphagia more than once per week within the last 3 months.; Diagnosed with Scleroderma; Diagnosed with an esophageal motility disorder such as but not limited to Achalasia, Nutcracker Esophagus, or Diffuse Esophageal Spasm or Hypertensive LES; Subject has a history of or known esophageal stricture or gross esophageal anatomic abnormalities (Schatzki's ring, obstructive lesions, etc.); Subject has esophageal or gastric varices; Subject has history of or known Barrett's esophagus; Cannot understand trial requirements or is unable to comply with follow-up schedule; Pregnant or nursing, or plans to become pregnant during the course of the study; Medical illness (i.e. congestive heart failure) that may cause the subject to be non-compliant with or able to meet the protocol requirements or is associated with limited life expectancy (i.e. less than 3 years); Diagnosed psychiatric disorder (e.g. bipolar, schizophrenia, etc.), subjects that exhibit depression that are on appropriate medication(s) are allowable.; Suspected or known allergies to titanium, stainless steel, nickel or ferrous materials; Subject has an electrical implant or metallic, abdominal implants
Sex/Gender	Sexes Eligible for Study: All
Ages	18 Years to 75 Years (Adult, Senior)
Accepts Healthy Volunteers	No
Contacts ICMJE	Contact information is only displayed when the study is recruiting subjects
Listed Location Countries ICMJE	Netherlands, United States
Removed Location Countries
Administrative Information
NCT Number ICMJE	NCT00776997
Other Study ID Numbers ICMJE	1802
Has Data Monitoring Committee	No
U.S. FDA-regulated Product	Not Provided
IPD Sharing Statement	Not Provided
Responsible Party	Torax Medical Incorporated
Study Sponsor ICMJE	Torax Medical Incorporated
Collaborators ICMJE	Not Provided
Investigators ICMJE	Not Provided
PRS Account	Torax Medical Incorporated
Verification Date	March 2018
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP