Evaluation of Safety and Effectiveness of the RefluxStop Device in the Management of GERD

• ClinicalTrials.gov Identifier: NCT02759094
• Recruitment Status: Unknown
• First Posted: May 3, 2016
• Last Update Posted: April 6, 2023
• Sponsor: Implantica CE Reflux Ltd.
• Information provided by (Responsible Party): Implantica CE Reflux Ltd.

Tracking Information

• First Submitted Date: April 15, 2016
• First Posted Date: May 3, 2016
• Last Update Posted Date: April 6, 2023
• Actual Study Start Date: December 2016
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: April 12, 2022)

• Primary safety endpoint [ Time Frame: at 6 months ]
  Assessment of incidence of serious adverse device effects (SADEs) and procedure-related serious adverse events (SAEs)
• Primary efficacy endpoint [ Time Frame: at 6 months ]
  Percent reduction from baseline of GERD symptoms based on the GERD-HRQL score (questions 1-10). The data will also be presented as the number of subjects obtaining a 50% improvement of the baseline figures, with success defined as 60% of the subjects to reach such score improvement. Thus, the aim of this analysis is to show that the lower limit of the confidence interval exceeds 60%.

Original Primary Outcome Measures (submitted: April 28, 2016)

• Assessment of incidence of serious adverse device effects (SADEs) and procedure-related serious adverse events (SAEs) [ Time Frame: through study completion, up to 6 months ]
• Assessment of percent reduction from baseline of GERD symptoms based on the GERD-HRQL score (questions 1-10) measured after the procedure [ Time Frame: Change from Baseline GERD symptoms to 6 months ]
  Efficacy endpoint

Current Secondary Outcome Measures (submitted: April 12, 2022)

• Secondary safety endpoint [ Time Frame: at 6 weeks, 3 months, 6 months (ADEs and AEs only) and annually years 1-5 ]
  Assessment of incidence of serious adverse device effects (SADEs) and procedure-related serious adverse events (SAEs). Incidence of adverse device effects (ADEs) and procedure-related adverse events (AEs)
• Secondary efficacy endpoint: HRQL all other timepoints [ Time Frame: measured at baseline, 6 weeks, 3 months and follow-up years 1-5 ]
  Percent reduction from baseline of GERD symptoms based on the GERD-HRQL score (questions 1-10)
• Secondary efficacy endpoint: additional questions [ Time Frame: measured at baseline, 6 weeks, 3 months, 6 months and follow up years 1-5 ]
  Reduction from baseline of GERD symptoms based on the total GERD-HRQL score (questions 1-10) and individual symptom questions
• Secondary efficacy endpoint: 24-hr pH monitoring [ Time Frame: measured at baseline, 6 months, 5 years and if therapy failure ]
  Reduction or normalisation from baseline of the total acid (pH<4) exposure time on 24-hour pH monitoring
• Secondary efficacy endpoint: PPI usage [ Time Frame: measured at baseline, 6 weeks, 3 months, 6 months and follow up years 1-5 ]
  Reduction from baseline of the percentage of subjects with regular daily PPI usage
• Secondary efficacy endpoint: Foregut [ Time Frame: measured at baseline, 6 weeks, 3 months, 6 months and follow up years 1-5 ]
  Reduction from baseline of individual foregut questionnaire scores focusing on regurgitation and additional information on dysphagia and odynophagia reported as AEs, or alternatively GERD-HRQL questions >2 and/or >3
• Secondary efficacy endpoint: Endoscopy [ Time Frame: measured at baseline, 6 months and if therapy failure ]
  Improvement in esophagitis on upper endoscopy
• Secondary efficacy endpoint: device location [ Time Frame: measured at hospital stay, 6 weeks, 6 months, 5 years and if therapy failure ]
  Location and function of the device evaluated by a simplified contrast swallow x-ray with overview pictures of device and LES position during swallowing

Original Secondary Outcome Measures (submitted: April 28, 2016)

• Assessment of incidence of adverse device effects (ADEs) and procedure-related adverse events (AEs) [ Time Frame: through study completion, up to 6 months ]
• Assessment of reduction from baseline of GERD symptoms based on the GERD-HRQL score (questions 1-10) measured after the procedure [ Time Frame: Change from Baseline GERD symptoms to 6 months ]
  Efficacy endpoint
• Assessment of reduction or normalisation from baseline of the total acid (pH<4) exposure time on 24-hour pH monitoring [ Time Frame: Baseline, 3 months FUP ]
  Efficacy endpoint
• Assessment of reduction from baseline in average daily PPI dosage after the procedure [ Time Frame: through study completion, up to 6 months ]
  Efficacy endpoint
• Assessment of reduction from baseline of foregut questionnaire scores after the procedure [ Time Frame: through study completion, up to 6 months ]
  Efficacy endpoint
• Assessment of improvement in oesophagitis on upper endoscopy [ Time Frame: Baseline, 3 months FUP ]
• Assessment of effectiveness of the device by a barium swallow examination [ Time Frame: Baseline, 6 weeks FUP, 6 months FUP ]
• Assessment of effectiveness (location and function) of the device by X-ray [ Time Frame: Baseline and after Implantation ]

Current Other Pre-specified Outcome Measures (submitted: April 12, 2022)

• Secondary efficacy subgroup endpoint [ Time Frame: per patient any point in the study triggered either by regular daily PPI usage or a GERD-HRQL score with less than 50% improvement compared to baseline, and having been verified as therapy failure via 24-hr pH monitoring and x-ray results ]
  Reduction or change comparison based on the following subgroups: age, gender, weight and result of baseline total GERD-HRQL score, comparing the following secondary endpoints: the total acid (pH<4) exposure time on routine 24-hour pH monitoring at month 6 and the number and percentage of subjects having verified therapy failure
• Exploratory endpoint: procedure complications [ Time Frame: during procedure ]
  Assess any procedure-related complications
• Exploratory endpoint: Procedure time [ Time Frame: during procedure ]
  Assess time to perform the procedure
• Exploratory endpoint: length of hospital stay [ Time Frame: from date of admission to date of discharge, assessed up to 100 months ]
  Assess length of the subject's hospital stay

• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Evaluation of Safety and Effectiveness of the RefluxStop Device in the Management of GERD
• Official Title: Evaluation of Safety and Effectiveness of the RefluxStop Device in the Management of Gastroesophageal Reflux Disease (GERD)

Brief Summary

Prospective, open-label, multi-centre, single arm treatment only trial to evaluate the safety and effectiveness of RefluxStop for the treatment of GERD.

The used medical device "RefluxStop" is an implantable single use sterile device to ensure maintenance of gastro oesophageal junction (GEJ) in an intra-abdominal position to reduce or eliminate GERD.

Detailed Description

The study plan will include a screening/baseline visit, a surgical procedure phase with hospital stay until discharge, and study visits at 6 weeks, 3 months and 6 months after device implantation.

A follow-up will be performed annually from years 1-5 to evaluate long-term safety and performance with the intention to collect post-market long-term data using the GERD-HRQL score as a screening tool. Data of subjects who agreed to participate in the long-term safety and performance will be analysed after 1, 2, 3, 4 and 5 years.

At the screening/baseline visit, after signing the informed consent, the eligibility of subjects to receive treatment with the study device will be determined. Eligible subjects will then undergo the device implant procedure.

A standard laparoscopic approach will be used to reposition the lower esophageal sphincter (LES) to its intra-abdominal position. The RefluxStop™ device will then be positioned and fixed in the gastric fundus to ensure intra-abdominal positioning of the GEJ at all time. After confirming proper placement, the laparoscopic implant procedure will be completed and access points will be closed. The procedure will be recorded and saved only with study identification number and without subject ID information. The same applies for images on contrast swallow controlling the device.

Evaluations will be performed daily during hospitalisation and in an additional 3 study visits in the outpatient setting at 6 weeks, 3 months and 6 months. Subjects who have given their consent to participate in the long-term safety and performance follow-up part of the study will be followed annually from year 1-5.

A pathologically low pH in the lower esophagus is correlated to the development of precancerous changes/ Barrett's esophagus and fulminant cancer, as shown in the literature. Barrett's esophagus occurs in 1-2% of the total population while daily acid reflux patients have an incidence of 10-20% depending on the severity of the acid reflux [Modiano, Gerson 2007; Cossentino, Wong 2003]. As many as 48,000 people p.a. die in Europe and the US alone of esophageal adenocarcinoma, the primary cause of which is acid reflux. Therefore, in order to determine whether treatment is maintained in the longer-term, an additional 24-hour pH monitoring and simplified contrast swallow x-ray to verify the position of the device will be performed at 5 years for the benefit of the patients.

These long-term results have also been requested by the U.S. FDA. A quality control of the placement of the device will be categorized for subjects at after surgery, 6 months and 5 year follow-up and at therapy failure.

The position of the device is of utmost importance and will be categorized in the case of therapy failure.

To ensure a proper quality control, the contrast swallow x-ray determining eventual hiatal hernia performed before surgery is repeated at hospital stay after surgery and during the 6-month surgical outcome control and at 5-year follow-up. This x-ray is also used for categorizing the position of the device in a four-graded scale if therapy failure occurs and should be performed by the radiologist using the standard of care post-op contrast swallow.

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: GERD

Intervention

Device: Treatment with RefluxStop

A standard laparoscopic approach will be used to reposition the lower oesophageal sphincter (LES) to its intra-abdominal position. The RefluxStop device will be then positioned and fixed in the gastric funds to ensure intra-abdominal positioning of the GEJ (Gastro-oesophageal Junction) at all time. After confirming proper placement, the laparoscopic implant procedure will be completed and access points will be closed.

Study Arms

Experimental: Treatment with RefluxStop device

All enrolled subjects will receive treatment for their GERD using the RefluxStop device intervention

Intervention: Device: Treatment with RefluxStop

• Publications *: Bjelovic M, Harsanyi L, Altorjay A, Kincses Z, Forsell P; Investigators of the RefluxStop Clinical Investigation Study Group. Non-active implantable device treating acid reflux with a new dynamic treatment approach: 1-year results : RefluxStop device; a new method in acid reflux surgery obtaining CE mark. BMC Surg. 2020 Jul 20;20(1):159. doi: 10.1186/s12893-020-00794-9.

Recruitment Information

• Recruitment Status: Unknown status
• Actual Enrollment (submitted: April 28, 2016): 50
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: December 2023
• Actual Primary Completion Date: March 2018 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• Subject's age >= 18 years and <= 75 years
• Subject is able to undergo general anaesthesia and is a suitable laparoscopic surgical candidate
• Subject is willing and able to participate
• Subject has provided written informed consent after being informed of the study procedure and risks prior to any study-related events
• Subject has documented typical GERD symptoms present for > 6 months which respond to PPIs as anti-GERD medication. Typical symptom of GERD is defined as heartburn, which is a burning epigastric or substernal pain
• Subject requires daily PPI anti GERD medication
• Subject has a 24-hour pH monitoring proven GERD performed taken off any anti reflux medication or after discontinuation for at least 7 days prior to testing. Total distal esophageal pH must be <= 4 for >= 4.5% if time during a 24-hour monitoring

Exclusion Criteria:

• Subject is currently participating in another study involving investigational drugs or devices
• Subject has a history of gastro esophageal surgery, anti-reflux or bariatric procedure
• Subject has a history of endoscopic anti-reflux intervention
• Subject has a history or a suspicion of esophageal or gastric cancer
• Subject has a history of major psychiatric disorder
• Presence of a para-esophageal hernia or sliding hernia of > 3cm determined on endoscopy
• Presence of an esophagitis grade C or D according to the Los Angeles classification
• Presence of esophageal dysmotility disorder such as but not limited to scleroderma, achalasia, Nutcracker oesophagus
• Presence of esophageal stricture or stenosis
• Presence of delayed gastric emptying
• Presence of esophageal or gastric varies
• Subject has a body mass index (BMI) > 35kg/m2
• Female subjects who are pregnant or nursing
• Known sensitivity or allergies to silicone materials
• Subjects who are unable to comply with the protocol requirements
• Subjects with limited life expectancy (< 3 years)
• Intra-operative findings that may preclude conduct of the study procedures

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 75 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Hungary, Serbia

Administrative Information

• NCT Number: NCT02759094
• Other Study ID Numbers: RXI 001
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Implantica CE Reflux Ltd.
• Original Responsible Party: Same as current
• Current Study Sponsor: Implantica CE Reflux Ltd.
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Principal Investigator: László Harsányi, Prof.; Semmelweis University

• PRS Account: Implantica CE Reflux Ltd.
• Verification Date: April 2022