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

NCT06721520 | Recruiting Phase 2 FDA Drug

• 1 other identifier: 24-898
• Study Type: interventional
• Target: 170
• Locations: 1 country
• Sites: 1

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.

Conditions

Esophageal Achalasia; Pylorus Dysfunction; Esophageal Dysmotility; Esophageal Cancer Surgery; Esophagectomy; Delayed Gastric Emptying Following Procedure; Esophageal Diseases

Keywords

Esophagectomy; Delayed gastric emptying; Delayed conduit emptying; Botox; botulinum toxin; Pyloromyotomy; Pyloric drainage

Outcome Measures

Primary Outcomes (1)

• Gastroparesis Cardinal Symptom Index (GCSI) total score at 6 months postoperatively or prior to the first reintervention (which ever 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.

  6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)

Secondary Outcomes (4)

• 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)

• Gastric emptying at 6 months postoperatively, measured by gastric emptying scintigraphy study (GES)

  6 months postoperatively

• 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)

• Pyloric reinterventions by 24 months post-operatively

  24 months postoperatively

Study Arms (2)

Botox

EXPERIMENTAL

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.

Biological: Botulinum Toxin A (Botox )

Pyloromyotomy

ACTIVE COMPARATOR

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.

Procedure: Pyloromyotomy

Interventions

Botulinum Toxin A (Botox ) BIOLOGICAL

Patients randomized for intrapyloric Botox injection will undergo the following standard procedure: 100 units of Botox are dissolved in 10 mL normal saline. After identifying the pylorus, the 10 mL of 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.

Botox

Pyloromyotomy PROCEDURE

Patients randomized for pyloromyotomy will undergo standard pyloromyotomy as follows: after identifying the pylorus, a 2-cm longitudinal incision is made with Metzenbaum or Mayo scissors on the anterior pylorus, centered on the pyloric ring. The incision extends through the serosa and muscular layers to expose the submucosa and mucosa, which is left intact. The cut muscle is spread apart until the submucosa bulges up to the level of the cut serosa. Care is taken to avoid perforation, and the surgeon confirms no mucosal perforation at the end of the procedure. If a perforation is encountered, it will be repaired primarily.

Pyloromyotomy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

RECRUITING

Related Publications (20)

• Khan OA, Manners J, Rengarajan A, Dunning J. Does pyloroplasty following esophagectomy improve early clinical outcomes? Interact Cardiovasc Thorac Surg. 2007 Apr;6(2):247-50. doi: 10.1510/icvts.2006.149500. Epub 2006 Dec 18.

  PMID: 17669829 BACKGROUND

• Urschel JD, Blewett CJ, Young JE, Miller JD, Bennett WF. Pyloric drainage (pyloroplasty) or no drainage in gastric reconstruction after esophagectomy: a meta-analysis of randomized controlled trials. Dig Surg. 2002;19(3):160-4. doi: 10.1159/000064206.

  PMID: 12119515 BACKGROUND

• Fok M, Cheng SW, Wong J. Pyloroplasty versus no drainage in gastric replacement of the esophagus. Am J Surg. 1991 Nov;162(5):447-52. doi: 10.1016/0002-9610(91)90258-f.

  PMID: 1951907 BACKGROUND

• Deng B, Tan QY, Jiang YG, Zhao YP, Zhou JH, Chen GC, Wang RW. Prevention of early delayed gastric emptying after high-level esophagogastrostomy by "pyloric digital fracture". World J Surg. 2010 Dec;34(12):2837-43. doi: 10.1007/s00268-010-0766-z.

  PMID: 20734044 BACKGROUND

• Arya S, Markar SR, Karthikesalingam A, Hanna GB. The impact of pyloric drainage on clinical outcome following esophagectomy: a systematic review. Dis Esophagus. 2015 May-Jun;28(4):326-35. doi: 10.1111/dote.12191. Epub 2014 Feb 24.

  PMID: 24612489 BACKGROUND

• Sutcliffe RP, Forshaw MJ, Tandon R, Rohatgi A, Strauss DC, Botha AJ, Mason RC. Anastomotic strictures and delayed gastric emptying after esophagectomy: incidence, risk factors and management. Dis Esophagus. 2008;21(8):712-7. doi: 10.1111/j.1442-2050.2008.00865.x. Epub 2008 Oct 1.

  PMID: 18847448 BACKGROUND

• Benedix F, Willems T, Kropf S, Schubert D, Stubs P, Wolff S. Risk factors for delayed gastric emptying after esophagectomy. Langenbecks Arch Surg. 2017 May;402(3):547-554. doi: 10.1007/s00423-017-1576-7. Epub 2017 Mar 21.

  PMID: 28324171 BACKGROUND

• Hajibandeh S, Hajibandeh S, McKenna M, Jones W, Healy P, Witherspoon J, Blackshaw G, Lewis W, Foliaki A, Abdelrahman T. Effect of intraoperative botulinum toxin injection on delayed gastric emptying and need for endoscopic pyloric intervention following esophagectomy: a systematic review, meta-analysis, and meta-regression analysis. Dis Esophagus. 2023 Oct 27;36(11):doad053. doi: 10.1093/dote/doad053.

  PMID: 37539558 BACKGROUND

• Konradsson M, Nilsson M. Delayed emptying of the gastric conduit after esophagectomy. J Thorac Dis. 2019 Apr;11(Suppl 5):S835-S844. doi: 10.21037/jtd.2018.11.80.

  PMID: 31080667 BACKGROUND

• Tcherniak A, Kashtan DH, Melzer E. Successful treatment of gastroparesis following total esophagectomy using botulinum toxin. Endoscopy. 2006 Feb;38(2):196. doi: 10.1055/s-2006-925148. No abstract available.

  PMID: 16479431 BACKGROUND

• Stewart CL, Wilson L, Hamm A, Bartsch C, Boniface M, Gleisner A, Mitchell JD, Weyant MJ, Meguid R, Gajdos C, Edil BH, McCarter M. Is Chemical Pyloroplasty Necessary for Minimally Invasive Esophagectomy? Ann Surg Oncol. 2017 May;24(5):1414-1418. doi: 10.1245/s10434-016-5742-x. Epub 2017 Jan 5.

  PMID: 28058546 BACKGROUND

• Giugliano DN, Berger AC, Meidl H, Pucci MJ, Rosato EL, Keith SW, Evans NR, Palazzo F. Do intraoperative pyloric interventions predict the need for postoperative endoscopic interventions after minimally invasive esophagectomy? Dis Esophagus. 2017 Apr 1;30(4):1-8. doi: 10.1093/dote/dow034.

  PMID: 28375478 BACKGROUND

• Tham JC, Nixon M, Ariyarathenam AV, Humphreys L, Berrisford R, Wheatley T, Sanders G. Intraoperative pyloric botulinum toxin injection during Ivor-Lewis gastroesophagectomy to prevent delayed gastric emptying. Dis Esophagus. 2019 Jun 1;32(6):doy112. doi: 10.1093/dote/doy112.

  PMID: 30561584 BACKGROUND

• Cerfolio RJ, Bryant AS, Canon CL, Dhawan R, Eloubeidi MA. Is botulinum toxin injection of the pylorus during Ivor Lewis [corrected] esophagogastrectomy the optimal drainage strategy? J Thorac Cardiovasc Surg. 2009 Mar;137(3):565-72. doi: 10.1016/j.jtcvs.2008.08.049.

  PMID: 19258066 BACKGROUND

• Martin JT, Federico JA, McKelvey AA, Kent MS, Fabian T. Prevention of delayed gastric emptying after esophagectomy: a single center's experience with botulinum toxin. Ann Thorac Surg. 2009 Jun;87(6):1708-13; discussion 1713-4. doi: 10.1016/j.athoracsur.2009.01.075.

  PMID: 19463583 BACKGROUND

• Bagheri R, Fattahi SH, Haghi SZ, Aryana K, Aryanniya A, Akhlaghi S, Riyabi FN, Sheibani S. Botulinum toxin for prevention of delayed gastric emptying after esophagectomy. Asian Cardiovasc Thorac Ann. 2013 Dec;21(6):689-92. doi: 10.1177/0218492312468438. Epub 2013 Jul 11.

  PMID: 24569327 BACKGROUND

• Eldaif SM, Lee R, Adams KN, Kilgo PD, Gruszynski MA, Force SD, Pickens A, Fernandez FG, Luu TD, Miller DL. Intrapyloric botulinum injection increases postoperative esophagectomy complications. Ann Thorac Surg. 2014 Jun;97(6):1959-64; discussion 1964-5. doi: 10.1016/j.athoracsur.2013.11.026. Epub 2014 May 1.

  PMID: 24793689 BACKGROUND

• Marchese S, Qureshi YA, Hafiz SP, Dawas K, Turner P, Mughal MM, Mohammadi B. Intraoperative Pyloric Interventions during Oesophagectomy: a Multicentre Study. J Gastrointest Surg. 2018 Aug;22(8):1319-1324. doi: 10.1007/s11605-018-3759-0. Epub 2018 Apr 17.

  PMID: 29667092 BACKGROUND

• Fuchs HF, Broderick RC, Harnsberger CR, Divo FA, Coker AM, Jacobsen GR, Sandler BJ, Bouvet M, Horgan S. Intraoperative Endoscopic Botox Injection During Total Esophagectomy Prevents the Need for Pyloromyotomy or Dilatation. J Laparoendosc Adv Surg Tech A. 2016 Jun;26(6):433-8. doi: 10.1089/lap.2015.0575. Epub 2016 Apr 4.

  PMID: 27043862 BACKGROUND

• Kent MS, Pennathur A, Fabian T, McKelvey A, Schuchert MJ, Luketich JD, Landreneau RJ. A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Surg Endosc. 2007 May;21(5):754-7. doi: 10.1007/s00464-007-9225-9. Epub 2007 Feb 16.

  PMID: 17458616 BACKGROUND

MeSH Terms

Conditions

Esophageal Diseases; Esophageal Achalasia; Esophageal Motility Disorders; Gastroparesis

Interventions

Botulinum Toxins, Type A; Pyloromyotomy

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases; Deglutition Disorders; Stomach Diseases; Paralysis; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Botulinum Toxins; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors; Endoscopy, Gastrointestinal; Endoscopy, Digestive System; Digestive System Surgical Procedures; Surgical Procedures, Operative; Gastrectomy; Myotomy

Study Officials

• Siva Raja, MD

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Andrew Conner, MD

CONTACT

216-316-6644; connera5@ccf.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 3, 2024
• First Posted: December 6, 2024
• Study Start: December 3, 2024
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): May 31, 2028
• Last Updated: February 25, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)