POEM-F for Achalasia International Study

Achalasia Clinical Trial

Official title:

Per-oral Endoscopic Myotomy With Fundoplication for Achalasia - an International Multicenter Randomized Controlled Trial

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06042127
• Other study ID #: 2023 145-T
• Status: Not yet recruiting
• Phase: N/A
• Start date: November 1, 2023
• Est. completion date: October 31, 2026

Study information

• Verified date: September 2023
• Source: Chinese University of Hong Kong
• Contact: Hon Chi Yip, FRCSEd
• Phone: 35052627
• Email: hcyip[@]surgery.cuhk.edu.hk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

Achalasia is the most common esophageal motility disorder worldwide, with an annual incidence of 1.6 per 100'000 individual and prevalence of 10 per 100'000 population. The incidence of achalasia has been dramatically rising over the past decade. A study conducted in Chicago suggested that over the 10 years from 2004 to 2014, the incidence and prevalence of achalasia were two- to threefold greater than estimates would have predicted. The likely explanation to the rise in incidence is an increased awareness of this condition and widespread availability of accurate diagnostic test with high resolution manometry. The cardinal features of achalasia include failed relaxation of lower esophageal sphincter and absent esophageal peristalsis. Owing to the benign nature of the disease, patients suffering from it would experience longstanding debilitating symptoms of dysphagia, chest pain, regurgitation, resulting in poor quality of life. In the past, laparoscopic Heller's cardiomyotomy with partial fundoplication and endoscopic pneumatic dilatation were considered as treatment options for achalasia.

In the past 10 years, per-oral endoscopic myotomy (POEM) has emerged as the incisionless minimally invasive endoscopic treatment of choice for achalasia. This Natural Orifice Transluminal Endoscopic Surgical (NOTES) technique involves mucosal incision and creation of a submucosal tunnel in the distal esophagus down to gastric cardia, followed by esophageal and gastric myotomy. Since the procedure was first reported by Inoue H, et al in 2010, it has seen worldwide acceptance as first-line therapy. POEM has been associated with excellent relief of dysphagia and achalasia-related symptoms with a low and acceptable adverse event rate of 0.5%. In a previous randomised controlled trial, POEM had a higher treatment success rate than pneumatic dilatation. When compared with laparoscopic Heller's cardiomyotomy, POEM was associated with at least similar treatment efficacy and a trend towards reduced short term adverse event. POEM could perform even better than surgical myotomy in patients with type III achalasia.

The main limitation of POEM is the incidence of gastroesophageal reflux disease (GERD) post-POEM. Kumbhari et al. looked at rates of GERD after POEM on patients who underwent subsequent objective pH testing. A total of 282 patients were included in this analysis from multiple centers in America, Asia, and Europe. About 58% of patients had objective evidence of abnormal acid exposure, with 23% showing evidence of esophagitis. More concerning, however, was that 60% of the patients with GERD were completely asymptomatic. This highlights an important issue at hand that many patients, either related to the propensity of GERD to be silent or the nature of achalasia to develop and insensate esophagus, do not report symptoms while showing high rates of GERD. POEM has been found to be consistently associated with higher rate of GERD than conventional Heller's cardiomyotomy or pneumatic dilatation across multiple studies.

Supported by evidence demonstrating the efficacy of partial fundoplication during Heller's operation, there has been a significant interest in performing fundoplication after POEM during the same session to prevent the development of post-POEM GERD. Inoue et al. pioneered the technique of POEM-F that mimics the surgical Dor (anterior partial fundoplication) procedure. In the pilot study, technical success was achieved in all 21 patients, and all but one had an intact fundoplication wrap on upper endoscopy at a 1-month follow-up. Four more studies conducted in Japan and India have reported good early outcomes with POEM-F (Technical success of 85-100%) for achalasia. No severe adverse event has been reported in these studies which reiterates the safety of this procedure. In the longest follow-up study on POEM-F, GERD diagnosed by an abnormal esophageal acid exposure was seen in 11.1% of the 21 cases at one-year follow-up: comparable (8.8%) to a large meta-analysis of 4871 Heller's cardiomyotomy with fundoplication procedures.

To date, no prospective multicenter randomised study has been conducted to compare the efficacy of POEM-F with conventional POEM in reducing post-procedure GERD. Therefore, in this study, the investigators aim to evaluate the of POEM-F in patients with achalasia through an international multicenter randomized controlled trial.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 81
• Est. completion date: October 31, 2026
• Est. primary completion date: October 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

Inclusion criteria:

1. Adult patient (age =18 and =65 years-old) and with symptomatic achalasia type I or II.

2. 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.

3. Patients with achalasia type I, II or III who are one of the following:

• Treatment naïve, or

• Failed prior through-the-scope balloon dilation, Savary or pneumatic dilation

Exclusion criteria:

1. Patients unable or unwilling to provide consent.

2. Previous esophageal or gastric surgery.

3. Prior achalasia treatment including Heller myotomy, POEM.

4. Sigmoid achalasia, or significant esophageal dilatation >6cm in lower esophagus

5. Disrupted mucosal integrity at the distal esophagus, eg. Ulcer, fibrotic scars etc

6. Patients with large hiatal hernias (axial length > 2 cm and Hill grade >2).

7. Patients with significant cardiorespiratory comorbidities which may limit their ability to undertake general anesthesia for the procedure, including ASA grade III or above.

8. Patients with obesity (Body Mass Index (BMI) = 30).

9. Pregnant women or those planning pregnancy or breastfeeding women.

10. Uncorrectable coagulopathy defined by international normalized ratio (INR) > 1.5 or platelet count < 50000/µl.

Related Conditions & MeSH terms

• Achalasia
• Esophageal Achalasia

Intervention

Procedure:
• POEM-F
POEM-F would be performed as described in the arms section
• Conventional POEM
Anterior POEM performed as described in the arms section

Locations

Country	Name	City	State
China	Nanfang Hospital, Southern Medical University	Guangzhou
Hong Kong	The Chinese University of Hong Kong	Hong Kong
India	Post Graduate Institute of Medical Education and Research	Chandigarh
India	Asian Institute of Gastroenterology	Hyderabad
India	Baldota Institute of Digestive Sciences	Mumbai
India	Deenanath Mangeshkar Hospital & Research Center	Pune
United States	Johns Hopkins Hospital	Baltimore	Maryland

Sponsors (7)

Lead Sponsor	Collaborator
Chinese University of Hong Kong	Asian Institute of Gastroenterology, India, Deenanath Mangeshkar Hospital and Research Centre, Johns Hopkins University, Nanfang Hospital, Southern Medical University, Northwestern University Feinberg School of Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh

Countries where clinical trial is conducted

United States,  China,  Hong Kong,  India, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Post-procedure rate of gastroesophageal reflux	Defined by updated Lyon 2.0 consensus as fulfilling one or more of the criteria: Endoscopic erosive esophagitis, LA grade B or above; Long segment Barrett's esophagus; Peptic esophageal stricture; 24-hour pH study with acid exposure time >6% Both endoscopy and pH study to be performed with proton pump inhibitor stopped for 4 weeks	1 year
Secondary	Clinical success rate of procedure	Post-treatment Eckhardt score <=3	1 year
Secondary	Adverse event of procedure	frequency of severe adverse events with probable or definite attribution to the procedure based on the American Society of Gastrointestinal Endoscopy (ASGE) lexicon as well as Clavien Dindo classification	30 day
Secondary	Technical success rate of procedure	Completing all steps of the intended procedure successfully in the same session	1 day
Secondary	Procedure time	Procedure time of the intended procedure in minutes	1 day
Secondary	Erosive esophagitis on post-procedure endoscopy	The presence of erosive esophagitis as well as the grading on post-procedure endoscopy	1 year
Secondary	Fundoplication wrap integrity on post-procedure endoscopy	Endoscopic appearance of fundoplication wrap on retroflexion in the stomach.; Intact - wrap is completely visualised; Indistinct - wrap is visualised but appears to be loosened; Absent - the wrap is completely not visible	1 year
Secondary	Distensibility index on EndoFLIP, premyotomy	Distensibility index (mm2/mmHg) using EndoFLIP	During index procedure, before myotomy
Secondary	Distensibility index on EndoFLIP, post myotomy	Distensibility index (mm2/mmHg) using EndoFLIP	During index procedure, after myotomy
Secondary	Distensibility index on EndoFLIP, post fundoplication	Distensibility index (mm2/mmHg) using EndoFLIP	During index procedure, after fundoplication
Secondary	Distensibility index on EndoFLIP, on follow-up	Distensibility index (mm2/mmHg) using EndoFLIP, at follow-up endoscopy	1 year
Secondary	Maximum diameter on EndoFLIP, premyotomy	Maximum diameter (mm) on EndoFLIP	During index procedure, before myotomy
Secondary	Maximum diameter on EndoFLIP, post-myotomy	Maximum diameter (mm) on EndoFLIP	During index procedure, after myotomy
Secondary	Maximum diameter on EndoFLIP, post-fundoplication	Maximum diameter (mm) on EndoFLIP	During index procedure, after fundoplication
Secondary	Maximum diameter on EndoFLIP, on follow-up	Maximum diameter (mm) on EndoFLIP, at follow-up endoscopy	1 year
Secondary	GERD-HRQL score	Symptom and quality of life score relating to GERD The score ranged from 0-50 with higher score signifying more severe GERD symptom / worse quality of life	1 month, 3 month, 6 month and 1 year
Secondary	GERD-RSI score	Symptom and quality of life score relating to GERD The score ranged from 0-45 with higher score signifying more severe GERD symptom	1 month, 3 month, 6 month and 1 year
Secondary	GERD-Q score	Symptom and quality of life score relating to GERD The score is ranged from 0-18 with the higher score signifying more symptom of GERD	1 month, 3 month, 6 month and 1 year
Secondary	Use of proton pump inhibitor post-procedure	Number of participants who are on regular / as required / not on PPI	1 month, 3 month, 6 month, and 1 year