RELIEF: LINX Reflux Management System in Subjects With GERD Who Have Previously Undergone a Laparoscopic Sleeve Gastrectomy

• Sponsor: Torax Medical Incorporated (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02429830
• Collaborator: (none)
• Enrollment: 30
• Locations: 12
• Arm: 1
• Actual Duration (Months): 50.1
• Patients Per Site: 2.5
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the LINX device in patients who have previously undergone laparoscopic sleeve gastrectomy (LSG) for obesity and have chronic gastroesophageal reflux disease (GERD). The study will monitor safety and changes in reflux symptoms.

Condition or Disease	Intervention/Treatment	Phase
GERD; Gastroesophageal Reflux Disease	Device: LINX device	N/A

Detailed Description

The objective of this study is to confirm safety and efficacy after laparoscopic sleeve gastrectomy (LSG) in subjects indicated for LINX is similar to the outcomes that formed the basis for the LINX Premarket Approval to support modification of the current labeling. Presently, there is a precautionary statement that safety and effectiveness of the LINX has not been established for prior esophageal or gastric surgery or endoscopic intervention.

Patients with GERD that have undergone a LSG procedure have limited surgical treatment options if they are looking for an alternative to continuous acid suppression therapy (i.e. proton pump inhibitors or equivalent). One procedure, fundoplication, is extremely difficult to perform as LSG patients have a limited amount of fundus tissue remaining after sleeve surgery. Roux-en-Y gastric bypass (RYGB) may be chosen as a conversion procedure but is more invasive with the potential for serious complications. LINX may be considered as an alternative and less invasive option that may potentially have few complications compared to RYGB.

The study is an observational, multicenter, single-arm study with prospective enrollment. Based on the observational status of the study, no formal statistical hypothesis tests will be conducted. Up to 30 patients meeting the eligibility requirements will be implanted with LINX and followed through 12-months after implant. Up to twelve (12) clinical sites will enroll subjects. Safety evaluations will be ongoing throughout the duration of the study, starting at the implant procedure. Efficacy endpoints will be evaluated at the 12-month visit.

Safety will be evaluated based on the rate of serious device and procedure related adverse events (AEs). Safety will also be evaluated by endoscopy to assess the mucosa and x-rays to verify device location at 12 months post implant. Efficacy will be measured at 12 months (compared to baseline) by examining 3 variables: normalization of total distal acid exposure or at least a 50% reduction, at least a 50% reduction in total GERD-HRQL scores and at least a 50% reduction in average daily PPI dosage.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Prospective, Multicenter Study of REflux Management With the LINX® System for Gastroesophageal REFlux Disease After Laparoscopic Sleeve Gastrectomy
• Actual Study Start Date: Apr 5, 2017
• Actual Primary Completion Date: Jun 8, 2021
• Actual Study Completion Date: Jun 8, 2021

Arms and Interventions

Arm	Intervention/Treatment
Other: Single arm study Previous LSG patient will be treated with the LINX device and serve as their own control	Device: LINX device; The LINX device is a permanent implant placed at the area of the lower esophageal sphincter (LES) and is designed to augment a weak LES and minimize or eliminate GERD-related symptoms.

Outcome Measures

Primary Outcome Measures

1. Percentage of Participants Reporting Greater Than or Equal to (>=) 50 Percent (%) Reduction in Total Gastroesophageal Reflux Disease (GERD)- Health-Related Quality of Life (HRQL) Score Compared to Baseline (Off GERD Medications) at the 12-month Follow-up [Up to 12 Months]

   Percentage of participants reporting >=50% reduction in total GERD-HRQL score compared to baseline (off GERD Medications) at the 12-month follow-up were reported. The GERD-HRQL score consisted of 10 questions, where participants were required to answer each question on a scale of 0 to 5 (0: no symptoms; 1: symptoms noticeable but not bothersome; 2: symptoms noticeable and bothersome but not every day; 3: symptoms bothersome every day; 4: symptoms affect daily activity; 5: symptoms are incapacitating, unable to do activities). The total score was derived by simply adding the individual score of each question. The total score ranged from 0 to 50 where a higher score indicated more severe disease. The best possible total GERD-HRQL score was 0 (asymptomatic in all questions) and the worst possible score was 50 (incapacitated in all questions).

2. Percentage of Participants Reporting Normalization of Total Distal Acid Exposure Time or at Least a 50% Reduction in Total Distal Acid Exposure Time Compared to Baseline at the 12-month Follow-up [Up to 12 months]

   Percentage of participants reporting normalization of total distal acid exposure time or at least a 50% reduction in total distal acid at the 12-month follow-up were reported. The testing was performed by a reflux sensing implantable capsule (for example, Bravo) or via a trans-nasal catheter. Success of the LINX device in decreasing abnormal levels of gastric acid in the esophagus was defined as normalization of distal acid exposure time (pH less than [<] 4 for greater than or equal to [>=] 4.5% of monitoring time) or at least 50% reduction in distal acid exposure time compared to baseline.

3. Percentage of Participants Reporting >=50% Reduction in Average Daily Protocol Pump Inhibitors (PPIs) Dosage Compared to Baseline at the 12-month Follow-up [Up to 12 months]

   Percentage of participants reporting >=50% reduction in average daily protocol pump inhibitors (PPIs) dosage compared to baseline at the 12-month follow-up were reported.

4. Number of Participants Experiencing Serious Device and/or Procedure Related Adverse Events After LINX Placement Out to 12 Months [Up to 12 months]

   Number of participants experiencing serious device and/or procedure related adverse events after LINX placement out to 12 months were reported. SAE is any AE that results in: requires subject hospitalization greater than (>) 24 hours; is life-threatening or results in death; 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 of body function or structure; other serious important medical events that do not fit in the other outcomes and may jeopardize the participant and may require medical or surgical intervention to prevent one of the other outcomes.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 22 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

INCLUSION CRITERIA

Subjects included in the study must meet all the following criteria:

1. Age >22 years

2. Laparoscopic sleeve gastrectomy (LSG) for obesity >12 months prior to proposed device implantation date.

3. Subject is a surgical candidate, i.e. is able to undergo general anesthesia and laparoscopic surgery.

4. Documented typical symptoms of GERD for longer than 6 months (regurgitation or heartburn which is defined as a burning epigastric or substernal pain which responds to acid neutralization or suppression).

5. Subject requires daily proton pump inhibitor or other anti-reflux drug therapy.

6. 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, with the exception of antacids up to the morning of testing.

1. Subjects with symptomatic improvement on PPI therapy demonstrated by a GERD-HRQL score of <10 on PPI and >15 off PPI, or subjects with a >6 point improvement when comparing their on PPI and off PPI GERD-HRQL scores.

2. GERD symptoms, in absence of PPI therapy (minimum 7 days).

3. 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.

4. Subject is willing and able to cooperate with follow-up examinations

5. Subject has been informed of the study procedures and the treatment and has signed an informed consent form.

EXCLUSION CRITERIA

Subjects should be excluded from the study based on the following criteria:

1. The procedure is an emergency procedure.

2. Suspected or known allergies to titanium, stainless steel, nickel, or ferrous materials.

3. Presence of ˃3 cm hiatal hernia as determined by endoscopy or barium esophagram.

4. Subject had any major complications related to the laparoscopic sleeve gastrectomy that may interfere with, or increase the risks of the LINX procedure (such as, but not limited to, leaks from the gastric remnant and infection at the sleeve gastrectomy)

5. Plans to surgically revise the gastric pouch (either known preoperatively or decided intraoperatively)

6. Currently being treated with another investigational drug or investigational device.

7. Suspected or confirmed esophageal or gastric cancer or prior gastric or esophageal surgery or endoscopic intervention for GERD (with the exception of sleeve gastrectomy).

8. Distal amplitude <35 mmHg or <70% peristaltic sequences (if using Conventional Manometry). -or- If using High Resolution Manometry (exclude for any of the following):

• Distal Contractile Integral (DCI) ≤ 450 mmHg·s·cm or

• ≥ 50% ineffective swallows or

• ≥ 50% fragmented swallows (Fragmented swallows are defined as those with a ≥ 5cm break [large] in peristaltic integrity).

1. Presence of esophagitis - Grade C or D (LA Classification).

2. BMI >35.

3. Symptoms of dysphagia more than once per week within the last 3 months.

4. Diagnosed with Scleroderma.

5. Diagnosed with an esophageal motility disorder such as but not limited to achalasia, nutcracker esophagus, or diffuse esophageal spasm or hypertensive LES.

6. Subject has a history of or known esophageal stricture or gross esophageal anatomic abnormalities (Schatzki's ring, obstructive lesions, etc.)

7. Subject has esophageal or gastric varices

8. History of/or known Barrett's esophagus. Note: The diagnosis of Barrett's esophagus requires both endoscopic and histologic evidence of metaplastic columnar epithelium. Endoscopically, there must be columnar epithelium within the esophagus. Histologically, the epithelium must be metaplastic, as defined by the presence of goblet cells.by

9. Subject cannot understand trial requirements or is unable to comply with follow-up schedule

10. Pregnant or nursing, or plans to become pregnant during the course of the study.

11. Any reason which the Investigator believes may cause the subject to be non-compliant with or unable to meet the protocol requirements.

12. Subject has an electrical implant or metallic, abdominal implants.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Northwest Allied Bariatric & Foregut Surgery	Tucson	Arizona	United States	85741
2	Mercy Health Northwest Arkansas	Rogers	Arkansas	United States	72758
3	Keck Medical Center of USC	Los Angeles	California	United States	90033
4	Institute of Esophageal and Reflux Surgery	Englewood	Colorado	United States	80113
5	RWJBH Univ. Hospital Somerset/Advanced Surgical and Bariatrics of NJ, PA	Somerset	New Jersey	United States	08873
6	Buffalo General Medical Center	Buffalo	New York	United States	14203
7	Adirondack Surgical Group	Saranac Lake	New York	United States	12983
8	East Carolina University	Greenville	North Carolina	United States	27834
9	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106
10	Coastal Carolina Bariatric & Surgical Center	Summerville	South Carolina	United States	29485
11	Panhandle Weight Loss Center	Amarillo	Texas	United States	79106
12	Gunderson Health System	La Crosse	Wisconsin	United States	54601

Sponsors and Collaborators

• Torax Medical Incorporated

Investigators

• Study Director: William J. Petraiuolo, MD, Ethicon Endo-Surgery

Study Documents (Full-Text)

• Study Protocol - Jul 25, 2018
• Statistical Analysis Plan - Sep 15, 2021

More Information

Publications

None provided.

• Responsible Party: Torax Medical Incorporated
• ClinicalTrials.gov Identifier: NCT02429830
• Other Study ID Numbers: 4600; TRX_2016_01
• First Posted: Apr 29, 2015
• Last Update Posted: Aug 10, 2022
• Last Verified: Aug 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes
• Keywords provided by Torax Medical Incorporated: gastroesophageal reflux disease; GERD; obesity; LSG; Laparoscopic Sleeve Gastrectomy
• Additional relevant MeSH terms: Gastroesophageal Reflux; Esophagitis, Peptic

Study Results

Participant Flow

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Period Title: Overall Study
STARTED	30
COMPLETED	27
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	47.1 (12.1)
Sex: Female, Male (Count of Participants)
Female	27 90%
Male	3 10%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	2 6.7%
Not Hispanic or Latino	28 93.3%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	2 6.7%
White	27 90%
More than one race	0 0%
Unknown or Not Reported	1 3.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Reporting Greater Than or Equal to (>=) 50 Percent (%) Reduction in Total Gastroesophageal Reflux Disease (GERD)- Health-Related Quality of Life (HRQL) Score Compared to Baseline (Off GERD Medications) at the 12-month Follow-up
Description	Percentage of participants reporting >=50% reduction in total GERD-HRQL score compared to baseline (off GERD Medications) at the 12-month follow-up were reported. The GERD-HRQL score consisted of 10 questions, where participants were required to answer each question on a scale of 0 to 5 (0: no symptoms; 1: symptoms noticeable but not bothersome; 2: symptoms noticeable and bothersome but not every day; 3: symptoms bothersome every day; 4: symptoms affect daily activity; 5: symptoms are incapacitating, unable to do activities). The total score was derived by simply adding the individual score of each question. The total score ranged from 0 to 50 where a higher score indicated more severe disease. The best possible total GERD-HRQL score was 0 (asymptomatic in all questions) and the worst possible score was 50 (incapacitated in all questions).
Time Frame	Up to 12 Months

Outcome Measure Data

Analysis Population Description

The Full Analysis Set (FAS) consisted of participants who met all eligibility criteria, provided informed consent, completed baseline assessments, and underwent a LINX procedure. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Measure Participants	26
Number [Percentage of participants]	80.8 269.3%

2. Primary Outcome

Title	Percentage of Participants Reporting Normalization of Total Distal Acid Exposure Time or at Least a 50% Reduction in Total Distal Acid Exposure Time Compared to Baseline at the 12-month Follow-up
Description	Percentage of participants reporting normalization of total distal acid exposure time or at least a 50% reduction in total distal acid at the 12-month follow-up were reported. The testing was performed by a reflux sensing implantable capsule (for example, Bravo) or via a trans-nasal catheter. Success of the LINX device in decreasing abnormal levels of gastric acid in the esophagus was defined as normalization of distal acid exposure time (pH less than [<] 4 for greater than or equal to [>=] 4.5% of monitoring time) or at least 50% reduction in distal acid exposure time compared to baseline.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

The FAS consisted of participants who met all eligibility criteria, provided informed consent, completed baseline assessments, and underwent a LINX procedure. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Measure Participants	27
Number [Percentage of participants]	44.4 148%

3. Primary Outcome

Title	Percentage of Participants Reporting >=50% Reduction in Average Daily Protocol Pump Inhibitors (PPIs) Dosage Compared to Baseline at the 12-month Follow-up
Description	Percentage of participants reporting >=50% reduction in average daily protocol pump inhibitors (PPIs) dosage compared to baseline at the 12-month follow-up were reported.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

The FAS consisted of participants who met all eligibility criteria, provided informed consent, completed baseline assessments, and underwent a LINX procedure. Here, 'N' (Number of participants analyzed) included all participants evaluable for this outcome measure.

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Measure Participants	24
Number [Percentage of participants]	95.8 319.3%

4. Primary Outcome

Title	Number of Participants Experiencing Serious Device and/or Procedure Related Adverse Events After LINX Placement Out to 12 Months
Description	Number of participants experiencing serious device and/or procedure related adverse events after LINX placement out to 12 months were reported. SAE is any AE that results in: requires subject hospitalization greater than (>) 24 hours; is life-threatening or results in death; 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 of body function or structure; other serious important medical events that do not fit in the other outcomes and may jeopardize the participant and may require medical or surgical intervention to prevent one of the other outcomes.
Time Frame	Up to 12 months

Outcome Measure Data

Analysis Population Description

The FAS consisted of participants who met all eligibility criteria, provided informed consent, completed baseline assessments, and underwent a LINX procedure.

Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
Measure Participants	30
Count of Participants [Participants]	2 6.7%

Adverse Events

Time Frame	Up to 12 months
Adverse Event Reporting Description	Full Analysis Set (FAS) consisted of participants who met all eligibility criteria, provided informed consent, completed baseline assessments, and underwent a LINX procedure.
Arm/Group Title	LINX Device
Arm/Group Description	Participants with gastroesophageal reflux disease (GERD) who previously underwent a laparoscopic sleeve gastrectomy were treated with the LINX Reflux Management System, a laparoscopic, fundic-sparing anti-reflux device designed to augment a weak lower esophageal sphincter (LES) and minimize or eliminate GERD-related symptoms.
All Cause Mortality
	LINX Device
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Serious Adverse Events
	LINX Device
	Affected / at Risk (%)	# Events
Total	2/30 (6.7%)
Gastrointestinal disorders
Dysphagia	1/30 (3.3%)	1
Surgical and medical procedures
Pain	1/30 (3.3%)	1
Other (Not Including Serious) Adverse Events
	LINX Device
	Affected / at Risk (%)	# Events
Total	15/30 (50%)
Gastrointestinal disorders
Dysphagia	5/30 (16.7%)	5
Nausea	2/30 (6.7%)	2
Diarrhea	1/30 (3.3%)	1
Esophageal spasm	1/30 (3.3%)	1
Epigastric pain and bloating	1/30 (3.3%)	1
Esophagitis	1/30 (3.3%)	1
General disorders
Vomiting, pain in chest and nausea	1/30 (3.3%)	1
Respiratory, thoracic and mediastinal disorders
Pneumothorax	1/30 (3.3%)	1
Foam pooling in throat	1/30 (3.3%)	1
Pleural effusion	1/30 (3.3%)	1
Post-Op Atelectasis & pleural effusion	1/30 (3.3%)	1
Skin and subcutaneous tissue disorders
Face tingling and pain	1/30 (3.3%)	1
Hypersensitivity to Dermabond	1/30 (3.3%)	1
Surgical and medical procedures
Pain	3/30 (10%)	3

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Neither the complete nor any part of the results of the study carried out under this protocol, nor any of the information provided by the Sponsor for the purposes of performing the study, will be published or passed on to any third party without the written consent of Sponsor. Any Investigator involved with this study is obligated to provide the Sponsor with complete test results and all data derived from the study.