The Evaluation of Effectiveness Between Empirical and Guided Therapy for Unexplained Non-Cardiac Chest Pain
Condition: Non Cardiac Chest Pain
MeSH terms: Chest Pain
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a prospective randomised clinical trial performed in a single center at Hospital
      Universiti Sains Malaysia (USM), Kelantan, Malaysia. Participants will be randomly allocated
      into either the empirical group or guided group for 8 weeks.The effectiveness in relieving
      chest pain (frequency and severity) will assessed after 2 weeks and 8 weeks of therapy with
      Gastroesophageal Reflux Disease Questionnaire (GERDQ) and Quality of Life Reflux and
      Dyspepsia (QOLRAD) questionnaire, and visual analogue scale (VAS) (score 1-10).
    

Detailed description: 
      Non-cardiac chest pain (NCCP) is very common in the general population but symptom alone or
      patient's characteristics do not adequately differentiate cardiac and esophageal cause.
      Cardiologists are usually consulted first to exclude life-threatening acute coronary
      syndrome. Tests that are performed to exclude ischemic heart disease include exercise stress
      test and the more invasive coronary angiography. A negative stress test or angiogram or the
      presence of mild blockage of a single vessel disease will usually be adequate to exclude
      significant ischemia as a cause for chest pain.

      The next most important cause of unexplained chest pain would be gastro-esophageal reflux
      disease (GERD). GERD and its complications of Barrett's oesophagus and oesophageal
      adenocarcinoma have increased markedly in recent decades, not just in the developed countries
      but also in Asia. Although relatively less common among populations in Malaysia, there are
      data to suggest an increasing prevalence of reflux disease largely a result of obesity and
      increased intra-abdominal pressure.

      Dexlansoprazole (Takeda Pharmaceuticals, Japan) is a novel dual delayed release system
      recently approved by the FDA for treatment of heartburn associated with non-erosive and
      erosive reflux disease. It is unknown if dexlansoprazole is effective as an empirical therapy
      for NCCP.

      Another approach would be therapy guided by investigations including high resolution (HR)
      esophageal impedance manometry and 24-hour pH-impedance studies. Study of esophageal function
      has greatly evolved with the recent availability of high resolution multi-channel solid state
      manometer and impedance. Water swallows are commonly used in esophageal manometric studies to
      evaluate for peristaltic abnormalities. Esophageal pH monitoring does not detect all
      gastroesophageal reflux (GER) events but with the combination of impedance, this technique
      allows detection of GER of gas and acid or non-acid liquids. These tests would enable
      diagnosis of GERD and functional chest pain and thereby allow targeted therapy.

      For treatment of GERD, dexlansoprazole is effective and for functional chest pain,
      nonspecific adenosine antagonist, theophylline is proven to improve symptoms in patient with
      hypersensitive esophagus. A selective serotonin reuptake inhibitor (SSRI) is also effective
      for functional chest pain , however it is not known if theophylline is more effective than
      any other SSRIs.It is unknown about the response rates based on the guided therapy approach
      compared to the empirical PPI therapy.

      Therefore, the aim of the intervention is to evaluate the effectiveness of empirical therapy
      vs. guided therapy on symptoms unexplained non-cardiac chest pain.
    

Intervention name(s): Empirical therapy group; Guided therapy group
Intervention type(s): Drug; Drug
Intervention description(s): Receive extended release lansoprazole (Dexlansoprazole, Takeda Pharmaceuticals, Japan) 60 mg daily for 2 weeks.; Receive Dexlansoprazole 30 mg daily for GERD, 60 mg daily for GERD with erosive esophagitis for 8 weeks and Theophylline SR 250 mg daily for functional chest pain for 4 weeks.
Other intervention name(s): Dexlansoprazole; Dexlansoprazole and/or Theophylline SR
Intervention MeSH terms: Theophylline; Dexlansoprazole; Lansoprazole
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomly allocated into either the empirical group or guided group for 8 weeks.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Non cardiac chest pain; Empirical therapy; Guided therapy