Clinical trial: A Randomized Trial of Medical and Surgical Treatments for Patients With GERD Symptoms That Are Refractory to Proton Pump Inhibitors (NCT01265550)

Eligibility criteria:
Inclusion Criteria:

          -  Age 18-70 years

          -  History of heartburn (defined as a burning sensation in the retrosternal area of the
             chest) that is refractory to antisecretory medications

          -  Initial GERD-HRQL:

               -  Total score must be at least 6 and at least one of the six heartburn questions
                  must be scored at least 2

          -  GERD-HRQL after two weeks of treatment with omeprazole:

               -  Total score must be >50% of the initial GERD-HRQL score and at least one of the
                  six heartburn questions must be scored at least 2

          -  Either or both of the following by baseline esophageal pH/multichannel intraluminal
             impedance (MII) monitoring in patients on omeprazole 20 mg two times a day (BID):

               -  Positive symptom association probability (SAP) (>95%) for acid reflux, non-acid
                  reflux or all reflux.

               -  Abnormal acid reflux (esophageal pH<4 for at least 4.2% of the 24-hour monitoring
                  period)

        Exclusion Criteria:

          -  Patients who do not have heartburn, defined as a burning sensation in the chest

          -  Patients unwilling or unable to provide informed consent

          -  Pregnancy or women unwilling to use effective contraception

          -  Age <18 or >70 years

          -  History of surgery on the stomach or esophagus

          -  History of seizure disorder

          -  History of heart block

          -  Allergy to or previous inability to tolerate study medications (omeprazole, baclofen,
             desipramine)

          -  Esophageal varices

          -  Cirrhosis

          -  Co-morbidity of sufficient severity to preclude elective surgery (e.g. pulmonary,
             cardiac, renal, liver disease)

          -  History of disorders that can cause medically-refractory "GERD symptoms" (eosinophilic
             esophagitis, neoplasms of the upper gastrointestinal tract, gastroparesis, achalasia)

          -  Myocardial infarction within the past 6 months

          -  History of schizophrenia

          -  Current use of clopidogrel

          -  Patients who have a contraindication to omeprazole or baclofen or who require therapy
             with a medication that has a clinically important drug interaction with omeprazole or
             baclofen.

          -  Patients who, in the judgment of the PI, are not suitable candidates for therapy with
             a study medication (omeprazole, baclofen, desipramine)

          -  Initial GERD-HRQL score: Total score <6 and/or all heartburn scores <2

          -  Inability to tolerate omeprazole during the 2-week treatment phase (before
             randomization)

          -  GERD-HRQL after two weeks of treatment with omeprazole: Total score less than or equal
             to 50% of initial GERD-HRQL score and/or all heartburn scores <2

          -  Laboratory abnormalities including:

               -  Platelet count <100,000

               -  international normalized ratio (INR) >1.5 (off anticoagulants)

               -  Serum creatinine >2.0 mg per deciliter

          -  Endoscopic abnormalities including:

               -  Los Angeles Classification of Oesophagitis (LA grade) C or D reflux esophagitis

               -  Active ulceration of the esophagus that is not due to reflux esophagitis

               -  Candida esophagitis

               -  Esophageal varices

               -  Active ulceration of the stomach and/or duodenum

               -  Neoplasm of the esophagus, stomach or duodenum

               -  Gastric outlet obstruction

               -  Eosinophilic esophagitis at least (15 eosinophils per high power field in any
                  esophageal biopsy specimen)

          -  Manometric abnormalities including:

               -  Achalasia

               -  Complete aperistalsis

          -  Negative SAP ( 95%) for acid reflux, non-acid reflux and all reflux on baseline
             combined esophageal pH/MII monitoring and normal acid reflux (esophageal pH<4 for
             <4.2% of the 24-hour monitoring period)

          -  Study surgeon identifies a contraindication to laparoscopic Nissen fundoplication

          -  Morbid obesity (BMI at least 40)

          -  Large paraesophageal hernia
No condition on gender to be admitted to the trial.
Accepts Healthy Volunteers
Subject must be at least 18 Years old.
Subject must be at most 64 Years

Patient description (medical language): A 48-year-old man comes to the office complaining of heartburn and acid reflux.  He has taken over-the-counter antacids but sees no relief.  Other medical history is unremarkable.  The patient does not use tobacco, alcohol, or illicit drugs.  Vital signs are within normal limits.  BMI is 31 kg/m2.  Physical examination is  positive for mild tenderness in upper stomach. Chest x-ray shows an air-fluid opacity behind the heart.  A barium swallow study reveals approximately 1/3 of the stomach herniating through the esophageal hiatus.

Patient description (patient's own words): I went to my doctor's office because of a non-stop heartburn and some acid reflux. I took over-the-counter medications, but it keeps going strong! I don't smoke, take drugs or drink alcohol, I'm healthy! The doctor took my vitals, which turned out normal. My BMI is 31, which might be a bit too much for a 48-year-old guy like me. They examined my stomach and found a mild tenderness in the upper part. I also did some X-rays, and they found out that I have an air-fluid opacity behind my heart. I did another X-ray, and it turns out that a part of my stomach went up my chest through a hole in my diaphragm!

Does the patient match the trial criteria? Entailment