Valvuloplasty as Alternative to Toupet Fundoplication for GERD

Study Overview
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Brief Summary
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This monocenter randomized controlled trial aims to compare postoperative outcomes of a laparoscopic valvuloplasty with a Toupet fundoplication in patients with GERD with a maximum hiatal hernia of 3cm. In addition, an economic evaluation of the new intervention will be done in order to determine cost-effectiveness and costs per quality-adjusted life-year (QALY).

Detailed Description
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This is a prospective, interventional, double-blinded, monocenter randomized controlled trial comparing a laparoscopic gastroesophageal valvuloplasty to laparoscopic Toupet fundoplication in patients with proven GERD with a maximum hiatal hernia of 3cm. In this design, both patient and researcher are blinded to the treatment allocation. Block randomization will be used to ensure an equal number in each treatment arm. Block randomization works by randomizing participants within blocks such that an equal number are assigned to each treatment. To reduce selection bias by predictability of the treatment allocation, random block sizes are used. Also the investigator is kept blind to the size of each block. A computer is used to generate 15 blocks for each participating center with random block sizes of 4, 8 and 12. Allocation proceeds by randomly selecting one of the orderings and assigning the next block of participants to study groups according to the specified sequence. Patients will be included during a two-year period and followed for a minimum of one year. When a patient is referred to a participating surgeon for antireflux surgery, he or she will receive study information to give them sufficient time for consideration. The surgeon will ensure all required pre-operative diagnostic tests are performed and that the indication for surgery is valid. During a follow-up visit, the surgeon ascertains that the patient complies with all inclusion criteria and does not meet any of the exclusion criteria. Study participation will be discussed and after informed consent is obtained, the patient will be included in the trial. After inclusion, the patient is immediately randomized but treatment allocation is not yet shared with the surgeon. The patient will receive validated questionnaires to record the pattern of symptoms, quality of life, medication and medical care usage. Data from the pre-operative tests will be recorded. On the day of surgery, the surgeon will be able to see treatment allocation and after performing the appropriate surgical procedure, records the course and specifics of the surgical procedure. Patients will receive a diary to record their meals and symptoms. Follow-up in the outpatient clinic will take place at the surgeon's discretion. At fixed moments: 3, 6 and 12 months after surgery, the patients will once more receive validated questionnaires. Also at about three months, a follow-up manometry and 24-hour pH and/or impedance monitoring will be performed. A power analysis was performed to calculate the sample size. Our primary aim was to compare the effect of both surgical procedures. Based upon the current medical literature, the objective/subjective success rate for the laparoscopic Toupet fundoplication is around 88%. Pilot data from a retrospective cohort of patients that underwent valvuloplasty report a subjective success rate of 96%. Our hypothesis was that the gastroesophageal valvuloplasty is not inferior to the Toupet fundoplication when comparing its effects on acid control. To prove non-inferiority of the valvuloplasty regarding acid reflux control, using a non-inferiority limit of 5%, 73 patients are required in each group. In all power calculations, a significance of 5% and power of 90% was used. To accommodate for a loss to follow-up of up to 10 percent, a total sample size of 160 was chosen.

Official Title
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Valvuloplasty as Alternative to Toupet Fundoplication for the Minimal Invasive Treatment of Gastroesophageal Reflux Disease: A Randomized Controlled Trial

Conditions
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Gastroesophageal Reflux, Hernia, Hiatal

Intervention / Treatment
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* Procedure: Laparoscopic gastroesophageal valvuloplasty
* Procedure: Laparoscopic Toupet fundoplication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Objectively proven GERD (by gastroscopy and/or 24-hour pH and/or impedance monitoring) Age ≥18 Written informed consent for study participation Exclusion Criteria: BMI ≥ 30 Hiatal hernia >3cm Achalasia Previous gastric surgery Previous esophageal surgery Inability to understand the Dutch language Inability to understand and/or fill in the questionnaires

Ages Eligible for Study
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Minimum Age: 18 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Laparoscopic valvuloplasty<br>Via laparoscopy, using three sutures a part of the esophagus is folded (similar to the way parts of a telescope slide in each other) into the stomach, creating a valve on the inside to prevent gastric acid to enter the esophagus. | Procedure: Laparoscopic gastroesophageal valvuloplasty<br> <br> |
| Active Comparator: Laparoscopic Toupet fundoplication<br>Via laparoscopy, the entire stomach is mobilized and folded around itself posteriorly, creating a partial (270 degrees) fundoplication. | Procedure: Laparoscopic Toupet fundoplication<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate, objective | Defined as % of patients with normal values of reflux measured by pH and impedance monitoring | 3 months post-operative | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Success rate, subjective | Defined as % of patients with Visick score I or II | 3 months post-operative, 1 year post-operative | 
| Percent of patients with complaints of functional dysphagia according to the Rome III criteria | % of patients with complaints of functional dysphagia according to the Rome III criteria. | 3 months post-operative, 1 year post-operative | 
| Cost-effectiveness | Cost-effectiveness will be calculated by comparing the direct and indirect medical cost related to both strategies up until one years after the operation. | 1 year post-operative | 
| Mortality rate | Defined as in-hospital mortality or out of hospital mortality within 30 days | 30 days | 
| Complication rate | Intra-operative complication rate | During surgery | 
| Conversion rate |  | During surgery | 
| Disease related reoperation rate | % of patients requiring redo surgery for persisting complaints or recurrence | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Valvuloplasty, Fundoplication, Acid reflux, GERD, Reflux disease, Hiatal hernia