Gastroesophageal Reflux Disease, Hiatal Hernia
Conditions
Keywords
GERD, Esophagitis, Fundoplication, Anti-reflux surgery, PPI dependent
Brief summary
The objective of the study is to evaluate the relative merits, safety and effectiveness of the EsophyX transoral device in performing an advanced TIF procedure in patients with troublesome symptoms as defined by the Montreal consensus definition while on PPIs compared with sham and placebo controls.
Detailed description
Primary Effectiveness Endpoint: A clinically significant reduction in GERD symptoms, specifically Troublesome regurgitation with or without heartburn assessed by the Reflux Disease Questionnaire (RDQ). Troublesome symptoms are those which occur a minimum of 2 days a week and are at least moderate in severity. Secondary Effectiveness Endpoint: The normalization of esophageal acid exposure at 6 months and a clinically significant reduction in PPI usage at 12 months.
Interventions
DEVICETIF Transoral Fundoplication
A novel surgical technique that creates a gastric fundoplication and restores competency of the gastroesophageal valve now exists for patients who have limited anatomic defects (small hiatal hernia). This technique is performed transorally using the EsophyX device (EndoGastric Solutions, Inc. Redmond, WA, USA) recreates a gastric fundoplication at the gastroesophageal junction by creating a flap valve at the intersection of the stomach and the esophagus by deploying polypropylene SerosaFuse fasteners (EndoGastric Solutions)
OTHERSham placebo procedure
The Sham Procedure (control) will consist of an upper GI endoscopy that will be conducted under general anesthesia in an operating room. The surgical team will follow the same steps before, during, and after the sham procedure similar to the TIF procedure, except they will never insert the EsophyX device into the patient. The endoscope will be manipulated for 30-45 min as if the device were around it to simulate the effect of many rotations and manipulations on the esophagus.
Sponsors
EndoGastric Solutions
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age 18-80 years * Dependent upon daily PPIs for \> 6 months * Troublesome symptoms, specifically heartburn or regurgitation, while on 40 mg of omeprazole or equivalent. Troublesome heartburn or regurgitation symptoms are those which occur a minimum of 2-3 days a week and are at least moderate in severity. * Abnormal ambulatory pH study off PPI therapy for 7 days. * Normal or near normal esophageal motility (by manometry) * Hiatal hernia axial height is no larger than 2 cm and the transverse dimension should not exceed 2.5 cm * Patient willing to cooperate with post-operative dietary recommendations and assessment tests * Signed informed consent
Exclusion criteria
* BMI \> 35 * Hiatal hernia \> 2 cm * Esophagitis Los Angeles grade C or D * Esophageal ulcer * Esophageal stricture * Esophageal motility disorder * Pregnancy or plans for pregnancy in the next 12 months (in females) * Immunosuppression * ASA \> 2 * Portal hypertension and/or varices * History of previous resective gastric or esophageal surgery, cervical spine fusion, Zenker's diverticulum, esophageal epiphrenic diverticulum, achalasia, scleroderma or dermatomyositis, eosinophilic esophagitis, or cirrhosis * Active gastro-duodenal ulcer disease * Gastric outlet obstruction or stenosis * Severe gastroparesis or delayed gastric emptying confirmed by solid-phase gastric emptying study if patient complains of postprandial satiety during assessment * Coagulation disorders * Interprocedural determination of anatomical presentation which in the opinion of the surgeon does not allow safe device introduction.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With a Clinically Significant Reduction in Gastroesophageal Reflux Disease (GERD) Symptoms (Specifically Troublesome Regurgitation With or Without Heartburn as Assessed by the RDQ Per the Montreal Consensus Definition, | 6 month follow up | Primary efficacy Hypothesis 1: At 6-month follow-up, the proportion of Transesophageal Incisionless Fundoplication (TIF)2+Placebo pts who are free of troublesome symptoms will be statistically significantly larger than those randomized to the Sham+PPI (Proton Pump Inhibitor) treatment group. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score | 6 months post procedure | DeMeester Score is a composite score taking into consideration reflux episodes, percentage of time pH is \< 4 and others. DMS was first reported in 1974 by Johnson and DeMeester. It is a composite score that measures acid exposure during prolonged ambulatory pH monitoring. The parameters that constitute the score are: 1. total number of episodes of reflux, - reflux is undesirable, therefore lower numbers are better, higher numbers are worse. Ideally there would be zero reflux episodes. 2. % total time esophageal pH \< 4, upright position and supine position, respectively - pH \< 4 is undesirable, therefor lower percentages are better 3. number of episodes longer than 5 minutes, - lower is better 4. maximal reflux duration, (reflux is undesirable - lower is better 5. total percentage of time with pH below 4 - below 4 is undesirable - lower is better The composite score can be obtained by adding the scores calculated for each of the six components. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham Placebo Procedure Sham Procedure: SHAM/PPI's An upper GI Endoscopy is performed with a standard endoscope, during 30-45 minutes. The patient is under general anesthesia. EGD explores the esophagus, the stomach, and the GEJ.
Sham placebo procedure: The Sham Procedure (control) will consist of an upper GI endoscopy that will be conducted under general anesthesia in an operating room. The surgical team will follow the same steps before, during, and after the sham procedure similar to the TIF procedure, except they will never insert the EsophyX device into the patient. The endoscope will be manipulated for 30-45 min as if the device were around it to simulate the effect of many rotations and manipulations on the esophagus. | 42 |
| TIF Transoral Fundoplication Intervention: TIF 2.0/Placebo TIF Transoral Incisionless Fundoplication: A fundoplication of 270 degrees and 3cm in length was created. The EsophyX device is introduced over a standard endoscope, through the mouth, into the stomach.
TIF Transoral Fundoplication: A novel surgical technique that creates a gastric fundoplication and restores competency of the gastroesophageal valve now exists for patients who have limited anatomic defects (small hiatal hernia). This technique is performed transorally using the EsophyX device (EndoGastric Solutions, Inc. Redmond, WA, USA) recreates a gastric fundoplication at the gastroesophageal junction by creating a flap valve at the intersection of the stomach and the esophagus by deploying polypropylene SerosaFuse fasteners (EndoGastric Solutions) | 87 |
| Total | 129 |
Baseline characteristics
| Characteristic | Sham Placebo Procedure | TIF Transoral Fundoplication | Total |
|---|---|---|---|
| Age, Continuous | 55 years | 52 years | 53 years |
| Region of Enrollment United States | 42 participants | 87 participants | 129 participants |
| Sex: Female, Male Female | 26 Participants | 40 Participants | 66 Participants |
| Sex: Female, Male Male | 16 Participants | 47 Participants | 63 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 42 | 0 / 87 |
| other Total, other adverse events | 0 / 42 | 4 / 87 |
| serious Total, serious adverse events | 1 / 42 | 3 / 87 |
Outcome results
Primary
Number of Participants With a Clinically Significant Reduction in Gastroesophageal Reflux Disease (GERD) Symptoms (Specifically Troublesome Regurgitation With or Without Heartburn as Assessed by the RDQ Per the Montreal Consensus Definition,
Primary efficacy Hypothesis 1: At 6-month follow-up, the proportion of Transesophageal Incisionless Fundoplication (TIF)2+Placebo pts who are free of troublesome symptoms will be statistically significantly larger than those randomized to the Sham+PPI (Proton Pump Inhibitor) treatment group.
Time frame: 6 month follow up
Population: Patients completing 6 month post-procedure follow-up
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sham Placebo Procedure | Number of Participants With a Clinically Significant Reduction in Gastroesophageal Reflux Disease (GERD) Symptoms (Specifically Troublesome Regurgitation With or Without Heartburn as Assessed by the RDQ Per the Montreal Consensus Definition, | 17 Participants |
| TIF Transoral Fundoplication | Number of Participants With a Clinically Significant Reduction in Gastroesophageal Reflux Disease (GERD) Symptoms (Specifically Troublesome Regurgitation With or Without Heartburn as Assessed by the RDQ Per the Montreal Consensus Definition, | 54 Participants |
p-value: <0.028Chi-squared
Secondary
Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score
DeMeester Score is a composite score taking into consideration reflux episodes, percentage of time pH is \< 4 and others. DMS was first reported in 1974 by Johnson and DeMeester. It is a composite score that measures acid exposure during prolonged ambulatory pH monitoring. The parameters that constitute the score are: 1. total number of episodes of reflux, - reflux is undesirable, therefore lower numbers are better, higher numbers are worse. Ideally there would be zero reflux episodes. 2. % total time esophageal pH \< 4, upright position and supine position, respectively - pH \< 4 is undesirable, therefor lower percentages are better 3. number of episodes longer than 5 minutes, - lower is better 4. maximal reflux duration, (reflux is undesirable - lower is better 5. total percentage of time with pH below 4 - below 4 is undesirable - lower is better The composite score can be obtained by adding the scores calculated for each of the six components.
Time frame: 6 months post procedure
Population: Patients that completed 6 month follow-up. NOTE: greater than 14.72 is considered abnormal, 14.72-50 is regarded as mild GERD, 51-100 is regarded as moderate GERD, and greater than 100 is regarded as severe GERD.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Sham Placebo Procedure | Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score | Pre-Procedure DeMeester Score | 30.9 Composite DeMeester Score |
| Sham Placebo Procedure | Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score | 6 month post-procedure DeMeester Score | 32.7 Composite DeMeester Score |
| TIF Transoral Fundoplication | Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score | Pre-Procedure DeMeester Score | 33.6 Composite DeMeester Score |
| TIF Transoral Fundoplication | Normalization of Esophageal Acid Exposure - as Measured by DeMeester Score | 6 month post-procedure DeMeester Score | 23.9 Composite DeMeester Score |