LINX Reflux Management System Clinical Study Protocol

Study Overview
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Brief Summary
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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
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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.

Official Title
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LINX Reflux Management System Clinical Study Protocol

Conditions
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Gastroesophageal Reflux

Intervention / Treatment
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* Device: Magnetic Sphincter Augmentation


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Magnetic Sphincter Augmentation<br>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. | Device: Magnetic Sphincter Augmentation<br>* 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.<br>* Other names: Magnetic Esophageal Sphincter;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of Occurrence for Device and Procedure Related Serious Adverse Events (SAEs). | 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. | through 24 months | 
| 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. | The analysis cohort for the primary efficacy analysis was the treated population which includes all implanted subjects and was determined through esophageal pH testing. | 12 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| At Least a 50% Reduction in Gastroesophageal Reflux Disease-Health-Related Quality of Life (GERD-HRQL) Total Score Compared to Baseline |  | 12 months | 
| Average Daily Proton-pump Inhibitor (PPI) Dosage Reduced by at Least 50% Compared to Baseline |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Gastroesophageal Reflux