Pneumodilation Or Endoscopic Myotomy in Achalasia trial

Achalasia is a rare motility disorder of the oesophagus that is characterised
by aperistalsis of the oesophageal body and dysrelaxation of the lower
oesophageal sphincter caused by progressive destruction and degeneration of the
neurons in the myenteric plexus. This leads to subsequent retention of food and
saliva in the oesophagus, resulting in the typical symptoms of achalasia such
as dysphagia, chest pain, regurgitation of undigested food and weight loss. The
cause of the neuronal degeneration found in achalasiais is unknown.
Treatment of achalasia is focused on symptom relief, which is obtained by
destroying the occluding function of the spastic lower oesophageal sphincter.
Treatment options are endoscopic dilatation by a pneumatic balloon, the golden
standard, or Heller myotomie a surgical treatment performed by laparoscopy.
Endoscopic pneumodilatation can be complicated by a perforation and there is a
relative high chance of symptom recurrence which requires subsequent treatment
sessions. The surgical treatment can also be associated with severe
complications, like a perforation, and is more invasive. Currently endoscopic
pneumodilatation is the first choice of treatment in patients with achalasia
and surgical myotomy is generally performed in case of symptom recurrence after
initial pneumodilatation. The recent developments on minimal invasive surgical
techniques has led to the development of per-oral endoscopic submucosal myotomy
(POEM) for the treatment of achalasia. The first results of the POEM are very
pe and suggest that this treatment is better than the endoscopic
pneumodilation, the golden standard.

To compare the efficacy of POEM to the efficacy of endoscopic pneumodilatation
as the initial treatment of symptomatic idiopathic achalasia. The treatment
succes is defined as symptom relief based on a Eckhardt score of 3 or less at 3
months, 1 year and 5 year after treatment. Furthermore there is an absence of
severe complications associated with the treatment and there is no need for
endoscopic or surgical retreatment between the first treatment en the primary
endpoint at two years after treatment.

Multicentre randomised clinical trial.

Study subjects undergo a POEM or endoscopic pneumodilatation

Per-oral endoscopic submucosal myotomy (POEM): The POEM tehcnique is entirely
endoscopic. Using an endoscopic knife, an entry to the submucosal space is made
in the oesophagus and after creating a submucosal tunnel towards the lower
oesophageal sphincter the circular muscle layers are cut. At the end of the
procedure the mucosal opening is closed with clips.

Endoscopic pneumodilatation: Endoscopic dilatation of the lower oesophageal
sphincter is performed by a Rigiflex balloon of 30mm and in case a second
dilatation is necessary a Rigiflex balloon of 35mm is used. A second dilatation
is performed if the Eckhardt symptomscore is above 3, three weeks after the
first dilatation or if at the the high resolution manometry the integrative
relaxation pressure (IRP4) is above the 10mmHg. A second dilatation within 6
weeks is not considered a failure but considered as a part of the regular
treatment.

For this study patients will be treated with a per-oral endoscopic submucosal
myotomy (POEM) or endoscopic pneumodilatation for the treatment of achalasia.
Both procedures are associated with risks, including a bleeding during or after
treatment, a perforation of the oesopahgus or stomach during the treatment and
an infection after treatment. These complications could be severe and need in
some cases immediately treatment. This may imply additional endoscopic or
surgical procedures with extension of admission time.

To determine long term effectiveness patients are followed for a period of five
years and need to undergo different oesophageal examinations like a
gastroscopy, a timed barium oesophagogram, high resolution manometry and a 24
hour pH-impedance monitoring. Furthermore they need to fill out questionnaires
regularly. After initial procedure study subjects need to visit the outpatient
clinic five times for follow-up.

The first results of the POEM are very promising and suggest that this
treatment is better than the endoscopic pneumodilation, the golden standard.
The risks of both procedures are the same. Furthermore patients that are not
participating in the trial will undergo a treatment anyway, in most cases this
will be endoscopic pneumodilatation.