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Esophageal Cancer SurgeryPhase 2/3EMPTYNCT06721520

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

A Phase 2/3 study testing Botulinum Toxin A (Botox ) and Pyloromyotomy in people with Esophageal Cancer Surgery and Esophagectomy, run by The Cleveland Clinic at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Botulinum Toxin A (Botox ) and Pyloromyotomy
Could I receive a placebo?
No, everyone receives an active treatment
How many people
170 participants
Where
1 siteUnited States
Study dates
3 Dec 2024to 31 May 2028
Phase
Phase 2/3
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Andrew Conner, MD contact

216-316-6644

connera5@ccf.org

United States1 site, 1 recruiting

  • Cleveland Clinic

    Cleveland, Ohio, 44195

    Andrew Conner, MD, 216-316-6644, connera5@ccf.org

    Recruiting

Other trials in United States

About this study

Official title: Comparative Effectiveness of Intrapyloric Botulinum Toxin Injection Versus Pyloromyotomy for Pyloric Drainage During Esophagectomy: A Registry-Based, Pragmatic Randomized Noninferiority Trial

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?

Read more

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.

Read the 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.

Being tested
Botulinum Toxin A (Botox ), Pyloromyotomy
Keywords
Esophagectomy, Delayed gastric emptying, Delayed conduit emptying, Botox, botulinum toxin, Pyloromyotomy, Pyloric drainage
Medical subject headings
Esophageal Diseases, Esophageal Achalasia, Esophageal Motility Disorders, Gastroparesis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • 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.

  • PyloromyotomyProcedure or surgery

    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.

Study groups in NCT06721520
Study groupRoleWhat they receive
BotoxExperimentalPatients 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.
Receives: Biological: Botulinum Toxin A (Botox )
PyloromyotomyActive comparatorPatients 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.
Receives: Procedure: Pyloromyotomy

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

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

Secondary outcomes (4)

  1. Complications in the immediate post-operative period (within 30 days post-operatively)

    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.

    Measured: 30 days postoperatively or until discharge from the index hospitalization (whichever duration is greater)

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

    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.

    Measured: 6 months postoperatively

  3. Cleveland Clinic Esophageal Questionnaire (CEQ) domain scores at 6-months postoperatively or prior to the first reintervention (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.

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

  4. Pyloric reinterventions by 24 months post-operatively

    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).

    Measured: 24 months postoperatively

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted6 Dec 2024
  2. Study start3 Dec 2024
  3. Primary completion31 Dec 2027 (estimated)
  4. Study completion31 May 2028 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Outcomes assessor
Enrolment
170 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06721520
Sponsor's protocol ID
24-898
Acronym
EMPTY
Status last verified
Feb 2026
First submitted
3 Dec 2024
Last updated
25 Feb 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 17669829

  • 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.

    PubMed 12119515

  • 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.

    PubMed 1951907

  • 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.

    PubMed 20734044

  • 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.

    PubMed 24612489

  • 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.

    PubMed 18847448

  • 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.

    PubMed 28324171

  • 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.

    PubMed 37539558

  • 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.

    PubMed 31080667

  • 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.

    PubMed 16479431

  • 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.

    PubMed 28058546

  • 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.

    PubMed 28375478

  • 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.

    PubMed 30561584

  • 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.

    PubMed 19258066

  • 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.

    PubMed 19463583

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing Botulinum Toxin A (Botox ) and Pyloromyotomy in people with Esophageal Cancer Surgery and Esophagectomy, run by The Cleveland Clinic at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 25 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Andrew Conner, MD (216-316-6644, connera5@ccf.org), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Gastroparesis Cardinal Symptom Index (GCSI) total score at 6 months postoperatively or prior to the first reintervention (which ever comes first) (time frame: 6 months postoperatively or prior to the first pyloric reintervention to treat symptoms of delayed gastric emptying postoperatively (whichever comes first)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06721520, which also lists 20 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Feb 2026.

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