To compare the efficacy of balloon dilatation (BD) and per oral endoscopic myotomy (POEM) in improving the symptoms of children with achalasia in short and long term Presently most guidelines such as American Society for Gastrointestinal Endoscopy (ASGE) or European Society for Gastrointestinal Endoscopy (ESGE) recommend POEM or LHM or BD for the management of achalasia cardia based on the institutional expertise and patient preference. Only the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) recommend POEM or LHM over PBD for the management of achalasia in children. This is due to the lack of pediatric randomised control trial comparing the efficacy and safety of the two methods both in long and short term.

Children 3-18 years of age diagnosed as a case of achalasia cardia Place of trial: Department of medical gastroenterology, AIG Hospitals, Gachibowli and Somajiguda/Banjara Hills Duration of the trial: 3-4 years Sample size: 70 (35 each arm) Inclusion criteria: All children diagnosed as a case of achalasia cardia aged 3-18 years Exclusion criteria: Children who have undergone prior BD or POEM or Heller's myotomy. Type 3 achalasia cardia. Prior oesophageal/gastric surgery. Coagulopathy. Patients refusing consent for the trial.

Primary outcome: Percentage of children with achalasia cardia achieving a clinical success of BD and POEM at 12 months post intervention (clinical success is Eckardt score ≤ 3 and timed barium esophagogram (TBE) showing a holdup at gastroesophageal junction of <5cm at 5 minutes without requirement of further intervention) Secondary outcomes: Major and minor treatment complications, percentage patients developing gastroesophageal reflux disease, procedure time and improvement in growth Randomization: A stratified block randomization shall be performed using computer generated random number tables BD arm: Children <7 years of age will under 1-2 sessions of BD 1month apart with CRE 20mm balloon. Children 7-17 years of age will undergo 1-2 sessions of BD with Rigiflex II, Achalasia balloon dilator (30mm followed by 35mm).

POEM arm: Children 3-17 years of age will undergo 1 session of POEM as per the unit protocol.

Outcomes will be assessed at 3,6,12 months of the index procedure Crossover: If Eckardt score >3 and TBE showing a stasis of >5cm at 5 minutes, treatment is considered to have failed and crossover will be offered Endpoints: One year of follow up from the initial intervention or one year of follow up of the crossover intervention (in case of treatment failure), major complications.

Interim analysis: Following completion of follow up of 50% of the trial participants Early termination of trial: In case of any treatment modality having >10% major complications or during interim analysis one treatment modality significantly better than other (p<0.003)

To compare the efficacy of balloon dilatation (BD) and per oral endoscopic myotomy (POEM) in improving the symptoms of children with achalasia in short and long term

Background:

Achalasia means "failure to relax". Achalasia cardia is a rare oesophageal motility disorder that occurs due to degeneration of the inhibitory myentric plexus of neurons of the oesophagus. This disorder is characterised by failure of relaxation of the lower oesophageal sphincter (LES), increased basal tone of the LES and absence of peristalsis in the oesophagus. All of these result in difficulty in passage of a food bolus from the oesophagus into stomach. Achalasia occurs in 0.1-0.18/100,000 per children per year.(1,2) Most patients present with symptoms of vomiting, dysphagia, chest pain and regurgitation. However, in children extra oesophageal symptoms such as chronic cough or aspiration is common. Smaller children may present with refusal to feed and failure to thrive. Achalasia cardia is a component of Allgrove syndrome and presents at an early age.(3) Treatment options for achalasia cardia include calcium channel blockers, botulinum injection, pneumatic balloon dilatation (BD), laparoscopic Hellers myotomy (LHM) and peroral endoscopic myotomy (POEM). BD, LHM and POEM are superior to the other therapies and should be offered to the patients when they are fit for the procedure. The type of achalasia, expertise of the centre and the patient preference should be taken into consideration before deciding on the modality of the treatment.(4) For type 3 achalasia cardia, POEM has been found to be superior when compared to BD or LHM.(4-7) However, for the other 2 types most guidelines don't provide a clear preference of one modality over the other. Major differences in the outcomes were not identified in between LHM and POEM in the systematic reviews and randomised control trials among type 1 and 2 achalasia.(8,9) Randomised control trials in adults have shown POEM to be superior to BD.(10,11) However, prospective comparative trials in children are lacking. A retrospective study by Tan Y et al showed BD to be as effective as POEM in short term (upto 1 year) but POEM was more effective on longer follow up.(12) Due to limited clinical trials and small sample sizes most guidelines advocate either of BD, LHM, POEM as the first line treatment modality for managing a patient with achalasia cardia on a case to case basis.(4-6) However, Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) recommends for POEM or LHM as the preferred modality over BD even in type 1 and 2 achalasia cardia. SAGES guidelines though recognises the lack of pediatric randomised trials comparing the three modalities of treatment and recommends for comparative pediatric studies in the future.(7) BD is also not standardised in children and there is no recommendation on the size of balloon to be used at a particular age. Commonly most studies treat children more than 6 years of age similar to adults. There is a lack of clarity on the treatment of children below this age. Multiple studies have used different balloons of different sizes with varying success. The absence of standard Rigiflex balloon smaller than 30mm complicates the matter. POEM however, has been found to be safe in children and has been performed in smaller children with good success.(13-20) However, due to technical difficulty it is not yet being performed as a standard of care at all centres. Thus, with these deficiencies in the literature, we planned for a randomised control trial to compare the outcomes of BD and POEM in children.

Rationale Presently most guidelines such as American Society for Gastrointestinal Endoscopy (ASGE) or European Society for Gastrointestinal Endoscopy (ESGE) recommend POEM or LHM or BD for the management of achalasia cardia based on the institutional expertise and patient preference. Only the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) recommend POEM or LHM over PBD for the management of achalasia in children. This is due to the lack of paediatric randomised control trial comparing the efficacy and safety of the two methods both in long and short term.

Study participants Children 3-18 years of age diagnosed as a case of achalasia cardia Design: Randomized control crossover trial Place of trial: Department of medical gastroenterology, AIG Hospitals, Gachibowli and Somajiguda.

Duration of the trial: 3-4 years Sample size: 70 (35 each arm)

Randomization: A stratified block randomization shall be performed using computer generated random number tables BD arm: Children <7 years of age will under 1-2 sessions of BD 1month apart with CRE 20mm balloon. Children 7-17 years of age will undergo 1-2 sessions of BD with Rig flex II, Achalasia balloon dilator (30mm followed by 35mm).

POEM arm: Children 3-17 years of age will undergo 1 session of POEM as per the unit protocol.

Outcomes will be assessed at 3,6,12 months of the index procedure Crossover: If Eckardt score >3 and TBE showing a stasis of >5cm at 5 minutes, treatment is considered to have failed and crossover will be offered Endpoints: One year of follow up from the initial intervention or one year of follow up of the crossover intervention (in case of treatment failure), major complications.

Interim analysis: Following completion of follow up of 50% of the trial participants Early termination of trial: In case of any treatment modality having >10% major complications or during interim analysis one treatment modality significantly better than other (p<0.003)

Inclusion Criteria:

-> All children of age 3-17 years diagnosed as a case of achalasia cardia

Exclusion Criteria:

• Children who had previously underwent BD, LHM or POEM
• Type 3 achalasia cardia. In children in whom HRM is not possible, if symptoms or barium oesophagogram is classical of type 3 achalasia, they will be excluded.
• Prior history of oesophageal or gastric surgery
• Coagulopathy
• Alternative diagnosis