Chest Pain Rule Out Myocardial Infarction Clinical Trial
Official title:
Proton Pump Inhibitor (PPI's) and Selective Serotonin Reuptake Inhibitor Therapy (SSRI's) for the Management of Non Cardiac Chest Pain (NCCP)
Non cardiac chest pain (NCCP) is defined as recurring, angina-like, retrosternal chest pain
of non cardiac origin. Annual prevalence of NCCP in the general population of the western
world ranges from 25-35%. Of those patients presenting to an emergency room with chest pain,
a cardiac etiology is ultimately found in only 11-39%. Several conditions are associated with
NCCP, with gastroesophageal reflux disease (GERD) being the most prevalent, constituting up
to 60% of cases. However, NCCP is considered a disorder of heterogenous nature and several
other conditions, apart of GERD, such as esophageal dysmotility and esophageal
hypersensitivity have been implicated.
Treatment of NCCP remains a real challenge due to the diverse underlying mechanisms
responsible for patients' symptoms. Given the fact that GERD is by far the most common
etiology, proton pump inhibitor (PPI) therapy has been tried extensively; however, after 6
weeks of treatment complete resolution of symptoms occurs in only 30% of patients, the
optimal duration of PPI administration is not known, while the best maintenance dose has
never been determined. Although the administration of selective serotonin reuptake inhibitors
(SSRIs) could theoretically benefit those patients with esophageal hypersensitivity, the
trials that have been published so far have included small number of patients and reported
conflicting results, while the co-administration of PPIs with SSRIs has not been evaluated so
far. Furthermore, data on treatment of patients with functional chest pain are lacking.
We have therefore designed a prospective study in order to evaluate the effect of PPI and
SSRI therapy for different subtypes of NCCP patients using multichannel intraluminal
impedance and pH (MII-pH) monitoring.
METHODS
Patients with non cardiac chest pain symptoms presenting to the participating centres, will
be prospectively screened for entry into the study.
They should have undergone a comprehensive diagnostic evaluation by cardiologists in order to
exclude a cardiac source for their chest pain. Patients recruited in the study should have
either a normal coronary angiogram or lack of ischemic heart disease on exercise treadmill or
stress thallium testing
Inclusion criteria i) patients should have at least 3 episodes of chest pain per week in the
previous 3 months.
The exclusion criteria will be:
i) thoracic, esophageal or gastric surgery ii) primary or secondary esophageal motility
disorders iii) use of non-steroidal anti-inflammatory drugs and aspirin iv) presence of
Barrett's esophagus, erosive esophagitis, peptic stricture and duodenal or gastric ulcer on
upper endoscopy v) eosinophilic esophagitis vi) underlying psychiatric illness vii) pregnancy
in women viii) refusal to participate.
Study protocol
All subjects who will agree to participate in the study should undergo an upper endoscopy to
assess the presence or absence of esophageal mucosal injury. Patients with Barrett's
esophagus and erosive esophagitis will not be included in the present study. Furthermore,
biopsies will be taken and patients with eosinophilic esophagitis will also be excluded.
All patients will also be subjected to stationary esophageal manometry and those with
motility abnormalities will be excluded. During esophageal manometry the lower esophageal
sphincter (LES) will be located.
Esophageal impedance-pH monitoring will be performed in all participating subjects using an
ambulatory multichannel intraluminal impedance (MII) and pH monitoring system (Sleuth;
Sandhill Scientific, Inc. Higland Ranch, CO, USA). During the test, each subject will eat
three standard meals, while the beginning and ending times of every meal will be indicated in
a diary. Subjects will also be instructed to press the event marker button on the data logger
whenever they experience chest pain. Data recording will be concluded after 24 hours, when
patients will return to the endoscopy unit for the catheter removal.
The impedance and pH data will be used to determine in each patient the number and type of
reflux episodes and the total 24-hour esophageal acid exposure, defined as the total time at
pH below 4 divided by the time monitoring. Total distal esophageal acid exposure (i.e., %
time pH < 4) less than 4.2% over 24 hours will be considered normal.
In each patient we will calculate the symptom index (SI) for chest pain. Bioview analysis
software will be used for the calculation of SI. According to the setting of this software
the symptoms will be considered as being related to reflux if they occur within a 2-min time
window after the onset of the reflux episode. SI will be defined as the number of symptoms
associated with reflux divided by the total number of symptoms. A positive SI is declared if
≥ 50% (i.e, at least half of the symptoms are associated with reflux).
Treatment
Patients will abnormal distal acid esophageal exposure will receive PPI twice daily for 8
weeks .
Patients with positive symptom index for chest pain will receive citalopram 20 mg once daily
and PPI once daily for 8 weeks.
Patients with a negative symptom index for chest pain will receive citalopram 20mg once daily
for 8 weeks.
All patients will be evaluated at the end of the 8-week period and will be asked about the
presence or absence of chest pain. Treatment success will be defined as the complete
disappearance of the chest pain, while the presence of mild or infrequent symptoms will be
considered as treatment failure.
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| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT02056964 -
HEART Pathway Implementation
|