Botox vs. Pyloromyotomy for Esophageal Cancer Surgery

(EMPTY Trial)

Overseen By Andrew Conner, MD

Age: 18+

Sex: Any

Trial Phase: Phase 2 & 3

Sponsor: The Cleveland Clinic

Disqualifiers: Neuromuscular disease, Pregnancy, Allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: During surgery

170 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if Botox (Botulinum Toxin A) can match the effectiveness of pyloromyotomy (a surgical cut to ease stomach drainage) in aiding proper stomach emptying after esophageal cancer surgery. Both treatments are tested to prevent delayed gastric emptying, which can cause post-surgery discomfort. Suitable candidates for this trial include those planning elective esophagectomy (surgery to remove part of the esophagus) and who can receive either Botox or pyloromyotomy during the procedure. Participants will be randomly assigned to one of the treatments and will complete follow-ups to monitor their symptoms over time. As a Phase 2, Phase 3 trial, this research measures the treatment's effectiveness in an initial, smaller group and represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking medical advancements.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Botox is generally safe for medical use. One study found that Botox injections for throat issues did not cause serious problems like ulcers or tears. Another review demonstrated that Botox worked well for conditions similar to those in this trial.

Pyloromyotomy has a long history of use, especially in stomach surgeries. As a standard procedure, its safety is well-established. Experienced surgeons performing it face no unexpected risks.

Both Botox and pyloromyotomy are well-tolerated in patients undergoing esophagus surgery. Evidence suggests that both treatments are safe, with Botox showing promise as an equally effective option. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the Botox and pyloromyotomy treatments for esophageal cancer surgery because they offer innovative approaches to managing postoperative complications. Unlike traditional pyloric drainage procedures, the Botox treatment involves injecting Botox directly into the pylorus, which may help relax the muscles and improve gastric emptying without the need for surgical incision. This minimally invasive approach could potentially reduce recovery time and surgical risks. On the other hand, pyloromyotomy, while a more traditional surgical method, is being directly compared to Botox to establish efficacy and safety, providing valuable insights that could refine standard care practices.

What evidence suggests that this trial's treatments could be effective for preventing delayed gastric emptying?

This trial will compare the use of Botox with pyloromyotomy during esophageal cancer surgery. Studies have shown that using Botox during surgeries like esophagectomies can help manage symptoms by assisting with stomach drainage. Botox relaxes muscles, aiding the stomach in emptying food more effectively. However, research suggests that Botox might not be as effective for some conditions compared to other treatments. Alternatively, pyloromyotomy, a surgical procedure, has traditionally improved stomach drainage by cutting the muscles at the stomach's exit point. This method has a proven track record for treating delayed stomach emptying. The trial will compare both treatments to determine if Botox can match pyloromyotomy in relieving symptoms after esophageal surgery. ^{1 2 4 6 7}

Who Is on the Research Team?

Siva Raja, MD

Principal Investigator

The Cleveland Clinic

Are You a Good Fit for This Trial?

This trial is for patients having elective esophagectomy due to benign or malignant esophageal conditions. They should not have other factors that could affect gastric emptying. Participants will be chosen randomly to receive either Botox injections or pyloromyotomy during surgery and will complete follow-up surveys.

Inclusion Criteria

I am undergoing surgery to reconstruct my digestive tract.

Willing and able to participate in long-term follow up including study visits and surveys

Willing and able to provide informed consent

Exclusion Criteria

I am having urgent surgery for a torn esophagus.

I have not had a specific type of stomach surgery called Sweet esophagectomy.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo esophagectomy with either intrapyloric Botox injection or pyloromyotomy for pyloric drainage

During surgery

1 visit (in-person, surgical procedure)

Immediate Post-operative Follow-up

Monitoring for complications such as anastomotic leaks, aspiration, and pneumonia within 30 days post-operatively

30 days

Follow-up

Participants are monitored for symptoms of delayed gastric emptying and quality of life at 3 months, 6 months, 1 year, and 2 years postoperatively

24 months

Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

• Botulinum Toxin A (Botox)
• Pyloromyotomy

Trial Overview

The study compares two stomach drainage methods after esophagectomy: intrapyloric Botox injection versus pyloromyotomy. It aims to determine if Botox is just as effective as pyloromyotomy in preventing delayed gastric emptying post-surgery.

How Is the Trial Designed?

Group I: Botox Experimental Treatment 1 Intervention

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.

Group II: Pyloromyotomy Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

The Cleveland Clinic

Lead Sponsor

Trials

1,072

Recruited

1,377,000+

Published Research Related to This Trial

In a study of 146 patients who underwent minimally invasive esophagectomy for esophageal cancer, the use of intraoperative pyloric procedures (pyloroplasty, pyloromyotomy, or botulinum toxin injections) did not show a clear advantage in reducing the need for postoperative endoscopic interventions, with 26% of patients requiring such interventions within six months.

Interestingly, while botulinum toxin injections were associated with the highest percentage of patients needing postoperative interventions, when adjusted for the type of esophagectomy performed, both the botulinum toxin and no intervention groups had lower rates of multiple postoperative interventions, suggesting that the choice of pyloric procedure may not significantly impact postoperative outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Do intraoperative pyloric interventions predict the need for postoperative endoscopic interventions after minimally invasive esophagectomy? Giugliano, DN., Berger, AC., Meidl, H., et al.[2017]

In a study of 71 patients undergoing minimally invasive esophagectomies, the use of botulinum toxin for chemical pyloroplasty did not significantly reduce the incidence of delayed gastric emptying compared to patients who did not receive the intervention, with rates of 8.6% and 5.6% respectively.

The study suggests that chemical pyloroplasty may not be necessary for improving outcomes in minimally invasive esophagectomy, as there were no significant differences in complications like aspiration pneumonia or the need for further pyloric interventions between the two groups.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is Chemical Pyloroplasty Necessary for Minimally Invasive Esophagectomy? Stewart, CL., Wilson, L., Hamm, A., et al.[2018]

In a study of 15 patients who underwent esophagectomy, injecting the pylorus with botulinum toxin was found to be a safe alternative to traditional pyloric drainage methods, with no cases of delayed gastric emptying or aspiration pneumonia in the perioperative period.

Most patients showed significant improvement in gastric emptying and were able to resume a regular diet, suggesting that botulinum toxin injection could effectively manage gastric outlet obstruction after esophagectomy, although further long-term studies are needed to assess its durability compared to conventional techniques.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A pilot study of botulinum toxin injection for the treatment of delayed gastric emptying following esophagectomy. Kent, MS., Pennathur, A., Fabian, T., et al.[2022]

Intrapyloric botulinum toxin injection significantly reduced operative time compared to standard procedures like pyloromyotomy and pyloroplasty, with mean times of 239 minutes versus 312 and 373 minutes, respectively.

However, patients receiving botulinum injections experienced more postoperative reflux symptoms (32% vs. 12% and 13%), required more promotility agents (22% vs. 5% and 15%), and had a higher need for endoscopic interventions, indicating that it may not be a safe or effective alternative to standard drainage procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intrapyloric botulinum injection increases postoperative esophagectomy complications. Eldaif, SM., Lee, R., Adams, KN., et al.[2014]

In a study of 25 patients undergoing esophagectomy for cancer, preoperative endoscopic pyloric balloon dilatation (EPBD) was performed without any complications, and no patients required additional surgery for gastric outlet obstruction postoperatively.

The results suggest that preoperative EPBD may effectively prevent pyloric stenosis, as only one patient needed a postoperative EPBD, indicating that this approach could eliminate the need for pyloroplasty during esophagectomy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endoscopic pyloric balloon dilatation obviates the need for pyloroplasty at esophagectomy. Swanson, EW., Swanson, SJ., Swanson, RS.[2021]

Pyloroplasty following elective esophagectomy appears to reduce the risk of gastric outlet obstruction and enhances gastric emptying, based on a review of one meta-analysis and six randomized controlled trials.

The procedure has a low incidence of complications, but its impact on other important outcomes like mortality, nutrition, and anastomotic leakage remains unclear.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Does pyloroplasty following esophagectomy improve early clinical outcomes? Khan, OA., Manners, J., Rengarajan, A., et al.[2007]

A simple risk score was developed to predict surgical mortality in esophageal cancer patients undergoing esophagectomy, based on an analysis of 3,592 patients across four cohorts, highlighting factors like age and comorbidities.

The score showed good calibration with observed mortality rates but had low discrimination, indicating it can help assess risk but may not be perfect in predicting individual outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Surgical mortality in patients with esophageal cancer: development and validation of a simple risk score. Steyerberg, EW., Neville, BA., Koppert, LB., et al.[2022]

In a study of 2,027 patients with T1 thoracic esophageal cancer, surgical treatment did not significantly improve survival compared to those who received radiotherapy (P=0.79).

Radiotherapy emerged as a significant independent prognostic factor for better outcomes in these patients (P=0.00059), suggesting it may be a more effective treatment option than surgery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Prognostic risk factors for T1 thoracic esophageal cancer: a retrospective cohort study. Wei, L., Xu, C., Gao, L., et al.[2022]

Involving trainees in esophagectomy procedures at high-volume centers can lead to acceptable clinical outcomes, with comparable preoperative characteristics and hospital stays for patients, indicating that training can be effectively integrated into surgical practice.

While there was a higher rate of anastomotic leaks in surgeries primarily performed by trainees (10.4%) compared to those by consultants (6.3%), this did not significantly impact overall morbidity or survival, suggesting that supervised trainee involvement does not adversely affect patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Impact of trainee involvement in esophagectomy on clinical outcomes: a narrative systematic review of the literature. Prasad, P., Navidi, M., Immanuel, A., et al.[2020]

In a study of 110 patients undergoing esophagectomy for esophageal cancer, the posterior mediastinal reconstruction route resulted in a significantly lower leakage rate (7.1%) compared to the retrosternal route (39%), indicating a safer option for surgical reconstruction.

Adjuvant radiotherapy did not affect the quality of life or postoperative functions of the gastric conduit in either reconstruction group, suggesting that the choice of reconstruction route is more critical for patient outcomes than the effects of radiotherapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reconstruction after esophagectomy for esophageal cancer: retrosternal or posterior mediastinal route? Chan, ML., Hsieh, CC., Wang, CW., et al.[2022]

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