POEM-F for Achalasia

Recruiting at 6 trial locations

Overseen By Hon Chi Yip, FRCSEd

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Chinese University of Hong Kong

Disqualifiers: Previous esophageal surgery, Obesity, Pregnancy, others

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

Compensation: Varies

Number of Visits: 2

Duration: 1 day

81 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Per-oral endoscopic myotomy (POEM) has emerged as the endoscopic treatment of choice for achalasia, offering comparable symptom relief with laparoscopic Heller's cardiomyotomy. The main concern with POEM is the higher incidence of post-procedure gastroesophageal reflux disease (GERD), occurring in up to 50-60% of patients. In order to reduce the risk of GERD, endoscopic fundoplication has been developed as a novel procedure mimicking surgical anterior partial fundoplication that can be performed in the same session as POEM (POEM-F). Case series of POEM-F in patients with achalasia reported encouraging outcomes of low GERD rate of \~12% at 1 year. Prospective comparative data between POEM-F and conventional POEM on post-procedure GERD is current lacking. The investigators therefore designed an international multicenter prospective randomized study to investigate the efficacy of POEM-F. The investigators postulate that POEM-F could reduce the incidence of post-procedure GERD when compared with conventional POEM. This is an international multicenter randomized controlled trial conducted between high volume expert centers from Hong Kong SAR, China, India and United States of America. Adult patients with manometry confirmed achalasia would be randomised to undergo POEM-F or POEM. The procedure would be performed by experts with vast experience in POEM. The primary outcome is the incidence of post-procedure GERD at 1 year, defined by the updated Lyon consensus. Secondary outcomes include technical and clinical success rates, adverse events, post-POEM endoscopic and manometry findings as well as patients' symptom scores. Sample size calculation Based on existing pilot comparative data on POEM-F and POEM, it is estimated that 84 patients would be required to demonstrate a difference in post-procedure GERD of 47.6% to 18.2%, with 80% power and false positive rate of 0.05, accounting for 10% loss to follow-up. Purpose and potential The current study proposal could demonstrate the superiority of POEM-F over POEM in reducing post-procedural GERD. It would also demonstrate the safety and reproducibility of the technique in expert centers across the globe. It could potentially replace conventional POEM as the preferred minimally invasive endoscopic treatment for achalasia.

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 the POEM procedure generally safe for humans?

The POEM procedure, used to treat achalasia, is generally considered safe, but it can lead to reflux-related symptoms over time. A large study analyzed adverse events in 1826 patients, indicating that while safety is still debated, it is a widely used treatment with a focus on understanding and managing potential risks. ^{1 2 3 4 5}

How is the POEM-F treatment for achalasia different from other treatments?

POEM-F is unique because it combines the POEM procedure, which is a minimally invasive endoscopic technique to treat achalasia, with fundoplication to reduce the risk of GERD (acid reflux) that can occur after the procedure. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment POEM-F for Achalasia?

Research indicates that adding fundoplication (a procedure to prevent acid reflux) to the standard POEM treatment may help reduce the risk of GERD (acid reflux) after the procedure, which is a common concern with POEM alone. Early studies in the U.S. show that this combined approach is technically feasible and safe. ^{1 6 10 11 12}

Who Is on the Research Team?

Hon Chi Yip, FRCSEd

Principal Investigator

Chinese University of Hong Kong

Are You a Good Fit for This Trial?

Adults aged 18-65 with symptomatic achalasia types I or II, who are either treatment-naive or have had unsuccessful balloon dilation. Excluded are those with prior esophageal surgery, significant comorbidities preventing anesthesia, obesity (BMI ≥ 30), pregnancy, breastfeeding, large hiatal hernias, or certain blood conditions.

Inclusion Criteria

Capability of understanding and complying with the study requirements, including filling the Eckardt Score, GERD-HRQL and RSI questionnaire and signing the informed consent form

I have achalasia and haven't been treated or my previous treatments didn't work.

Exclusion Criteria

I have damage to the lining of my lower esophagus, like ulcers or scars.

My BMI is 30 or higher.

I have serious heart or lung conditions that make anesthesia risky for me.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo either POEM-F or conventional POEM procedure

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including assessment of GERD and other outcomes

1 year

Multiple visits (in-person and virtual) at 1 month, 3 months, 6 months, and 1 year

Long-term Follow-up

Extended monitoring of GERD and other outcomes beyond the primary follow-up period

Additional 6 months

What Are the Treatments Tested in This Trial?

Interventions

• Conventional POEM
• POEM-F

Trial Overview The trial compares two procedures for achalasia: conventional POEM and a new method called POEM-F which includes an endoscopic fundoplication to potentially reduce gastroesophageal reflux disease (GERD) after the procedure. It's an international study measuring GERD incidence one year post-treatment.

How Is the Trial Designed?

Group I: Per-oral endoscopic myotomy with fundoplication Experimental Treatment 1 Intervention

The detail of the procedure has been reported in the literature. After completion of myotomy as per conventional anterior POEM, a serosal incision would be made at the level of the GE junction below the diaphragmatic crus. The peritoneal cavity would then be entered and the anterior gastric wall could be identified. A detachable endoloop would be introduced alongside the endoscope with the guidance of endoscopic clip. Three to four clips would be applied to the anterior gastric fundus while additional 3-4 clips would be applied to the edge of the submucosal tunnel, all anchoring to the endoloop. Upon tightening of the endoloop the anterior fundus would be approximated to the esophagogastric junction and thus completing the partial anterior fundoplication. Abdominal paracentesis to treat capnoperitoneum would be performed as required based on patient's clinical condition.

Group II: Conventional POEM Active Control 1 Intervention

Conventional per-oral endoscopic myotomy An anterior POEM would be performed per usual manner described in the literature. The procedure would be performed under general anaesthesia by expert endoscopists with at least 50 case experience of conventional POEM and 5 cases experience of POEM-F. The requirement of POEM experience is based on a recent multicenter study of learning curve by Fujiyoshi Y, et al. The procedure would follow the current recommendations from expert panel in reducing GER, including avoidance of excessive gastric myotomy and preservation of the sling fibers are the gastric cardia. The length of the esophageal and gastric myotomy is standardized at 5cm and 2cm respectively

Conventional POEM is already approved in European Union, United States, India, China for the following indications:

Approved in European Union as POEM for:

• Esophageal achalasia

Approved in United States as POEM for:

• Esophageal achalasia

Approved in India as POEM for:

• Esophageal achalasia

Approved in China as POEM for:

• Esophageal achalasia

Who Is Running the Clinical Trial?

Chinese University of Hong Kong

Lead Sponsor

Trials

1,387

Recruited

1,372,000+

Deenanath Mangeshkar Hospital and Research Centre

Collaborator

Trials

1

Recruited

80+

Johns Hopkins University

Collaborator

Trials

2,366

Recruited

15,160,000+

Northwestern University Feinberg School of Medicine

Collaborator

Trials

42

Recruited

15,500+

Asian Institute of Gastroenterology, India

Collaborator

Trials

99

Recruited

63,500+

Post Graduate Institute of Medical Education and Research, Chandigarh

Collaborator

Trials

311

Recruited

118,000+

Nanfang Hospital, Southern Medical University

Collaborator

Trials

571

Recruited

4,591,000+

Post Graduate Institute of Medical Education and Research, Chandigarh

Collaborator

Trials

2

Recruited

180+

Published Research Related to This Trial

The peroral endoscopic myotomy with fundoplication (POEM-F) procedure was technically feasible in a study of 20 patients, achieving an 85% technical success rate and a median procedure time of 118 minutes.

While POEM-F showed reasonable short-term outcomes, including 58.8% of patients off proton pump inhibitors, concerns about the durability of the fundoplication and complications like fundal wrap loosening and ulceration highlight the need for further long-term studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Early outcomes of peroral endoscopic myotomy with fundoplication for achalasia cardia - Is it here to stay? Patil, G., Dalal, A., Maydeo, A.[2021]

In a study of 31 patients undergoing per oral endoscopic myotomy (POEM) for achalasia, the procedure showed significant improvement in symptoms, with average preoperative Eckardt scores of 6.3 dropping to 2.2 after one year, indicating effective treatment.

The multidisciplinary approach to POEM resulted in a low average hospital stay of 1.3 days and a low complication rate, demonstrating both safety and efficiency in adopting this technique for achalasia management.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per oral endoscopic myotomy: early experience and safety of a multispecialty approach. Arshava, EV., Marchigiani, RJ., Gerke, H., et al.[2019]

The study involved 21 patients undergoing a new procedure called POEM+F, which combines peroral endoscopic myotomy with endoscopic fundoplication to address gastroesophageal reflux (GER) after standard POEM treatment.

POEM+F was successfully performed in all cases without any immediate or delayed complications, suggesting it is a safe and effective minimally invasive option for treating achalasia while potentially reducing the risk of GER.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peroral endoscopic myotomy and fundoplication: a novel NOTES procedure. Inoue, H., Ueno, A., Shimamura, Y., et al.[2023]

Using optical coherence tomography (OCT) before per-oral endoscopic myotomy (POEM) in 51 patients significantly reduced procedural bleeding compared to a control group, with only 8% experiencing bleeding versus 43% in the control group.

The use of OCT also led to a shorter procedural time, averaging 85.8 minutes compared to 121.7 minutes in the control group, indicating that OCT can enhance the safety and efficiency of the POEM procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Optical coherence tomography (OCT) prior to peroral endoscopic myotomy (POEM) reduces procedural time and bleeding: a multicenter international collaborative study. Desai, AP., Tyberg, A., Kedia, P., et al.[2018]

The study of six patients undergoing peroral endoscopic myotomy with fundoplication (POEM-F) for achalasia showed that the procedure was technically successful in all cases, indicating its feasibility.

No major adverse events occurred within 30 days post-procedure, and significant improvements in symptoms were observed, with a marked reduction in the Eckardt score, suggesting effective treatment with a low risk of complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Technical details and outcomes of peroral endoscopic myotomy with fundoplication: the first U.S. experience (with video). Shrigiriwar, A., Zhang, LY., Ghandour, B., et al.[2023]

In a study of 1,826 patients undergoing peroral endoscopic myotomy (POEM), the overall prevalence of adverse events (AEs) was found to be 7.5%, with severe AEs occurring in only 0.5% of cases, indicating that POEM is relatively safe when performed by experienced endoscopists.

Factors such as having a sigmoid-type esophagus, the endoscopist's experience (less than 20 cases), and the type of knife and electrosurgical current used were identified as significant predictors of AEs, highlighting the importance of technique and expertise in minimizing risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comprehensive Analysis of Adverse Events Associated With Per Oral Endoscopic Myotomy in 1826 Patients: An International Multicenter Study. Haito-Chavez, Y., Inoue, H., Beard, KW., et al.[2022]

The study demonstrated that the combined procedure of per-oral endoscopic myotomy with fundoplication (POEM+F) was successfully performed on three patients with achalasia, indicating its technical feasibility.

No major adverse events were reported during or after the procedure, and the maintenance of the surgical wrap was confirmed at one-month follow-up, suggesting a promising approach to reduce reflux symptoms associated with traditional POEM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per oral endoscopic myotomy with fundoplication is a technically feasible NOTES for achalasia cardia. Mandavdhare, HS., Samanta, J., Varma, P., et al.[2022]

Per-oral endoscopic myotomy (POEM) demonstrated a high treatment success rate of over 90% at 12 months, although this decreased to 84% at 24 months, indicating it is an effective long-term treatment for achalasia.

However, more than one-third of patients experienced mild reflux symptoms or esophagitis post-procedure, highlighting the need for monitoring and potential management of reflux after POEM.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety. Martinek, J., Svecova, H., Vackova, Z., et al.[2019]

In a study of 33 patients undergoing peroral endoscopic myotomy (POEM) for esophageal motility disorders, 92% of achalasia patients and 75% of non-achalasia patients experienced significant improvement in dysphagia, demonstrating the efficacy of POEM in treating these conditions.

The procedure was found to be safe, with no mortality and a low complication rate (5.7%), while also allowing for flexible adjustments in the myotomy length and location, making it a versatile option for various esophageal motility issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal motility disorders. Hoppo, T., Thakkar, SJ., Schumacher, LY., et al.[2022]

Per-oral endoscopic myotomy (POEM) is a minimally invasive and effective treatment for achalasia, with clinical remission rates ranging from 82% to 100%, and it shows similar outcomes to laparoscopic Heller myotomy in terms of perioperative and short- to long-term results.

The procedure is generally safe, with no reported deaths and a complication rate comparable to traditional surgery, but it requires specialized training due to its technical complexity and potential risks such as bleeding and perforation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Per-oral endoscopic myotomy (POEM): a new endoscopic treatment for achalasia. Miranda García, P., Casals Seoane, F., Gonzalez, JM., et al.[2018]

Peroral endoscopic myotomy (POEM) is a safe and effective treatment for esophageal achalasia in children, as demonstrated by a study involving three children with an average age of 9.6 years, where no postoperative complications occurred.

After undergoing POEM, the two patients who were followed for 12 months experienced complete relief of symptoms and a significant reduction in lower esophageal sphincter pressure, indicating the procedure's efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peroral endoscopic myotomy for the treatment of achalasia in children. Familiari, P., Marchese, M., Gigante, G., et al.[2022]

In a study of 300 patients who underwent peroral endoscopic myotomy (POEM) for achalasia, routine postoperative chest CT scans revealed a high frequency of minor findings, such as pneumomediastinum (48%) and pneumoperitoneum (37%), which were often clinically irrelevant.

Only a small percentage of patients required intervention for complications, with 5.6% needing treatment for pneumothorax and 0.7% for pleural effusion, suggesting that routine CT scans may not be necessary after POEM, especially when using CO2 instead of air to minimize risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Thoracic CT after peroral endoscopic myotomy for the treatment of achalasia. Cai, MY., Zhou, PH., Yao, LQ., et al.[2016]

Citations

1. Australia pubmed.ncbi.nlm.nih.gov

Early outcomes of peroral endoscopic myotomy with fundoplication for achalasia cardia - Is it here to stay? [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Per oral endoscopic myotomy: early experience and safety of a multispecialty approach. [2019]

3. Germany pubmed.ncbi.nlm.nih.gov

Peroral endoscopic myotomy and fundoplication: a novel NOTES procedure. [2023]

4. Germany pubmed.ncbi.nlm.nih.gov

Optical coherence tomography (OCT) prior to peroral endoscopic myotomy (POEM) reduces procedural time and bleeding: a multicenter international collaborative study. [2018]

5. United States pubmed.ncbi.nlm.nih.gov

Technical details and outcomes of peroral endoscopic myotomy with fundoplication: the first U.S. experience (with video). [2023]

6. United States pubmed.ncbi.nlm.nih.gov

Comprehensive Analysis of Adverse Events Associated With Per Oral Endoscopic Myotomy in 1826 Patients: An International Multicenter Study. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Per oral endoscopic myotomy with fundoplication is a technically feasible NOTES for achalasia cardia. [2022]

8. Germany pubmed.ncbi.nlm.nih.gov

Per-oral endoscopic myotomy (POEM): mid-term efficacy and safety. [2019]

9. Germany pubmed.ncbi.nlm.nih.gov

A utility of peroral endoscopic myotomy (POEM) across the spectrum of esophageal motility disorders. [2022]

10. Spain pubmed.ncbi.nlm.nih.gov

Per-oral endoscopic myotomy (POEM): a new endoscopic treatment for achalasia. [2018]

11. United States pubmed.ncbi.nlm.nih.gov

Peroral endoscopic myotomy for the treatment of achalasia in children. [2022]

12. United States pubmed.ncbi.nlm.nih.gov

Thoracic CT after peroral endoscopic myotomy for the treatment of achalasia. [2016]