Effectiveness of Methods for Pyloric Drainage in esophagecTomY: Botox vs. Pyloromyotomy

Phase 2

Not yet recruiting

• Conditions: Esophageal Cancer Surgery; Esophagectomy; Delayed Gastric Emptying Following Procedure; Esophageal Diseases; Esophageal Achalasia; Pylorus Dysfunction; Esophageal Dysmotility
• Interventions: Biological: Botulinum Toxin A (Botox ); Procedure: Pyloromyotomy

• Registration Number: NCT06721520
• Lead Sponsor: The Cleveland Clinic

Brief Summary

The goal of this pragmatic, registry-based, randomized clinical trial is to find out if using botulinum toxin (Botox) to help drain the stomach during an esophagectomy works as well as a pyloromyotomy in patients undergoing elective esophagectomy for benign or malignant esophageal disease. Both methods are intended to prevent problems with food emptying too slowly from the stomach (delayed gastric emptying), which can cause discomfort after surgery. The main question it aims to answer is:

Is intrapyloric Botox injection as a drainage procedure during esophagectomy non-inferior in preventing symptoms of delayed gastric emptying at 6 months postoperatively compared to pyloromyotomy?

Researchers will compare intrapyloric Botox injection to pyloromyotomy to see if Botox is non-inferior to pyloromyotomy in easing symptoms of delayed gastric emptying.

Participants will:

Be randomized to one of two treatment groups-either intrapyloric Botox injection or pyloromyotomy-during their esophagectomy.

Complete surveys assessing digestive symptoms at standard postoperative follow-up intervals (3 months, 6 months, 1 year, and 2 years postoperatively).

Undergo a standard gastric emptying study at 6 months after surgery.

Detailed Description

This is a single institution, pragmatic, registry-based, prospective, single-blinded, randomized, double-arm, noninferiority clinical trial comparing outcomes of two standard-of-care alternative intraoperative methods of pyloric drainage during esophagectomy. One arm of the study will be patients receiving intervention 1, intrapyloric Botox injection (Botox Group), and the other arm will be patients receiving intervention 2, pyloromyotomy (Pyloromyotomy Group). Participants will be allocated equally to the interventions being compared (allocation ratio 1:1).

Patients randomized for intrapyloric Botox injection will undergo our standard procedure as follows: 100 units of Botox is dissolved in 10 mL normal saline. After identifying the pylorus during esophagectomy, 10 mL of the Botox solution is injected intramuscularly at the anterior pyloric ring in 2 separate areas and in 1 area on each side of the pyloric ring (total 4 areas). Patients randomized for pyloromyotomy will undergo standard pyloromyotomy through a transabdominal, anterior approach.

This study will occur at Cleveland Clinic Foundation in Cleveland, OH. Three staff surgeons will perform these operations.

Study Timeline

• Status Verified: 2024-12
• Study Start: 2024-12-01
• Study First Submitted: 2024-12-03
• Study First Submitted QC: 2024-12-03
• Last Update Submitted: 2024-12-03
• Study First Posted: 2024-12-06
• Last Update Posted: 2024-12-06
• Primary Completion: 2027-12-31
• Study Completion: 2028-05-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 170

Inclusion Criteria

• 18 years of age or older
• Undergoing elective esophagectomy (thoracoabdominal, Ivor-Lewis, McKeown)
• Receiving a gastric conduit for alimentary reconstruction
• Technically able to receive either intrapyloric Botox injection or pyloromyotomy as ultimately determined intraoperatively
• Willing and able to provide informed consent
• Willing and able to participate in long-term follow up including study visits and surveys

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Exclusion Criteria

• Undergoing emergent esophagectomy (e.g., for esophageal perforation)
• Patients with underlying neuromuscular disease as Botox would be contraindicated (amyotrophic lateral sclerosis, myasthenia gravis, muscular dystrophies, Lambert-Eaton syndrome)
• Patients undergoing left thoracoabdominal without left cervical neck incision (i.e., Sweet esophagectomy) - excluded due to the extent of gastric resection
• Pregnancy
• Allergy or hypersensitivity to botulinum toxin
• Cannot feasibly receive both pyloric interventions as determined intraoperatively (e.g., patients with central obesity undergoing thoracoabdominal esophagectomy makes for a technically difficult pyloromyotomy)

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Botox	Botulinum Toxin A (Botox )	Patients will be randomized to the intrapyloric Botox injection intervention arm intraoperatively just after the pylorus is identified and just prior to the time at which pyloric drainage would occur routinely, at which point it is feasible for the surgeon to perform either intervention.
Pyloromyotomy	Pyloromyotomy	Patients will be randomized to the pyloromyotomy intervention arm intraoperatively just after the pylorus is identified and just prior to the time at which pyloric drainage would occur routinely, at which point it is feasible for the surgeon to perform either intervention.

Primary Outcome Measures

Name	Time	Method
Gastroparesis Cardinal Symptom Index (GCSI) total score at 6 months postoperatively or prior to the first reintervention (which ever comes first)	6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)	The GCSI is a validated 9-item instrument used to quantify severity of symptoms associated with delayed gastric emptying. The GCSI is based on three subscales, which measure cardinal symptoms related to delayed gastric emptying: postprandial fullness/early satiety (4 items), nausea/vomiting (3 items), and bloating (2 items). A 6-point Likert-type response scale, ranging from 0 (none) to 5 (very severe) is used for rating the severity of each symptom item, with a recall period of 2 weeks. Subscale scores are calculated by averaging across the item scores within each subscale. The range of subscale scores is 0 to 5, where higher scores reflect perception of worse symptom severity. The GCSI total score is constructed as the average of the three symptom subscales scores. GCSI. GSCI scores will be obtained preoperatively and at 3-month, 6-month, 1-year, and 2-year follow up, with 6 months as the specific time point for our primary endpoint.

Secondary Outcome Measures

Name	Time	Method
Complications in the immediate post-operative period (within 30 days post-operatively)	30 days postoperatively or until discharge from the index hospitalization (whichever duration is greater)	Perioperative complications include gastroesophageal anastomotic leaks, pyloric leaks, aspiration, pneumonia, respiratory failure, cardiac arrhythmia, myocardial infarction, cardiac failure, mortality, and readmission within 30 days for nausea/vomiting or pneumonia. These outcomes are routinely recorded by trained registry personnel at our institution as part of national quality reporting requirements.
Gastric emptying at 6 months postoperatively, measured by gastric emptying scintigraphy study (GES)	6 months postoperatively	At 6 months postoperatively, a 4-hour solid-phase GES, considered the gold standard for assessing gastric motility, will be obtained as per our institute's standard of care and interpreted by Cleveland Clinic radiologists. The study consists of administering a low-fat, egg-white meal containing technetium-99m sulfur colloid labeled egg albumin. Gastric retention of the egg meal is measured at baseline and at 1, 2, and 4 hours after consumption and the results are reported as a retained percentage. Also included in the radiology report is the half-emptying time, or the time the stomach requires to empty 50% of the ingested radiolabeled test solid meal, which is commonly used to assess gastric emptying in post-esophagectomy studies. Due to the non-linear nature of gastric emptying, we will also use the percentage of food retained at 4 hours as an additional measure, which has been a marker of delayed gastric emptying in previous research.
Cleveland Clinic Esophageal Questionnaire (CEQ) domain scores at 6-months postoperatively or prior to the first reintervention (whichever comes first)	6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)	The impact of symptom severity on patient quality of life (QoL) will be assessed by Cleveland Clinic Esophageal Questionnaire (CEQ) raw domain scores. The CEQ is a validated patient-reported outcome measure that allows for quantification of esophageal symptoms and their impact on the patient's quality of life. The CEQ is comprised of 34 items divided into 6 domains: dysphagia (7 items), eating (7 items), pain (5 items), reflux/regurgitation (5 items), dyspepsia (4 items), and dumping (6 items). Each item is accompanied by a question regarding frequency of symptoms, with a 6-point Likert-type response option ranging from 1 (never) to 6 (several times a day) and a question regarding the symptom's impact on quality of life, with a 5-point Likert-type response option ranging from 1 (not at all) to 5 (a lot). We will obtain the raw scores across each domain at baseline preoperatively and at 3-months, 6-months, 1-year, and 2-years follow-up, per our institution's standard of care protocol.
Pyloric reinterventions by 24 months post-operatively	24 months postoperatively	After esophagectomy, patients reporting severe symptoms related to delayed gastric emptying, determined based upon standard clinical evaluation (i.e., patients with a moderate or large amount of retained food on routine, post-operative upper endoscopy after fasting for 8 hours and reporting severe regurgitation or having an aspiration pneumonia event), will be offered further endoscopic treatment of their delayed gastric emptying, per our institute's standard of care protocol. We will compare frequency of reinterventions up until 24-months postoperatively in each arm. Per our institution's protocol, all of these patients, regardless of which treatment arm they are in, initially receive endoscopic Botox injection. If their gastric emptying improves, demonstrated by improvement of GCSI score or decrease in amount of retained food on upper endoscopy, and they do not have symptoms of dumping syndrome, they are then offered gastric per-oral endoscopic pyloromyotomy (G-POEM).

Trial Locations

Locations (1)

Cleveland Clinic; 🇺🇸 Cleveland, Ohio, United States