Which Supraesophageal Reflux Symptoms Reliably Respond to Proton-Pump-Inhibitor (PPI) Therapy
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
|Official Title:||Which Supraesophageal Reflux Symptoms Reliably Respond to PPI Therapy: A Large Simple Trial|
- To determine which symptom(s) are predictive of SER based on a complete response to PPI therapy [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
- To determine which symptoms demonstrate partial response with PPI therapy [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
- To determine which features of a patient's history are predictive of a positive response to PPI therapy [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
- To determine which features of a patient's history are predictive of a lack of response to PPI therapy [ Time Frame: 1 month ] [ Designated as safety issue: Yes ]
- To develop a scoring system for the Supraesophageal Reflux Questionnaire (SRQ) that would predict a diagnosis of SER [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]
|Study Start Date:||April 2005|
|Study Completion Date:||August 2006|
|Primary Completion Date:||August 2006 (Final data collection date for primary outcome measure)|
|Placebo Comparator: Sugar pill||
Drug: Sugar Pill
40 mg BID
|Active Comparator: Active Comparator||
40 mg bid dosing
Hide Detailed Description
Estimates suggest that up to 50% of Voice Clinic patients and 10% of ENT and Pulmonology outpatients seek medical care for chronic laryngopharyngeal symptoms resulting from supraesophageal reflux (SER). While many anecdotal and uncontrolled studies have shown significant clinical benefit with Proton Pump Inhibitors (PPIs), this conclusion has not been supported in small, randomized, placebo-controlled studies. The recent negative Vaezi trial (unpublished) was limited by bias introduced in the patient enrollment process due to reliance on physician diagnosis of SER. This bias became clear during conduction of the Supraesophageal Reflux Questionnaire (SRQ) Validation Study (Mayo, in press), which demonstrated that Otolaryngologists vary in their threshold for considering the diagnosis of SER. This project aims to remove selection bias from the study design.
Hypotheses/Questions: Our underlying assumptions are as follows: SER is due to the passage of gastric contents into the esophagus; and with adequate acid suppression provided by a PPI, there is less overall volume available to reflux, which should improve SER. We hypothesize that persons with the particular cluster of symptoms that are due to SER will have complete resolution of those symptoms with adequate acid suppression when PPI is administered for an adequate duration of time.
- To determine which symptom(s) (chronic cough, hoarseness, sore throat, globus sensation, or throat clearing) are completely ameliorated with PPI therapy and hence reflective of SER.
- To determine which features of a patient's history are predictive of a positive response to PPI therapy, and which confer lack of response; and
- To develop a scoring system for the SRQ that would predict a diagnosis of SER.
Design: Large simple randomized, double-blind, placebo-controlled trial of subjects with chronic laryngopharyngeal symptoms.
Population: Subjects will be recruited from Olmsted County and from General ENT Clinic and Pulmonary Chronic Cough Clinic.
Inclusion Criteria: Subjects must have at least 1 of 5 chronic (present for at least one month) and recurrent (at least twice per week) symptoms of interest.
Randomization: A dynamic allocation algorithm will be used by the Mayo Pharmacy to balance the treatment arms for confounding variables for treatment allocation.
Study Intervention: Either twice daily esomeprazole 40 mg or placebo for 6 months. Beyond a urine pregnancy test for women of child-bearing age, no other examination is required for enrollment or participation.
Follow-Up: Subjects will be contacted by phone monthly to assess symptoms, check compliance, and adverse events.
Primary Outcome: True responders will be those subjects who lack at least one of their initial symptoms by the 3-month time period, and remain asymptomatic at 4, 5 and 6 months.
Sample Size: Based on previous studies we anticipate a 30-40% placebo response rate at 3 months that will not be sustained at 6 months. We expect roughly 60% to completely respond to PPI therapy (i.e. 40% do not completely respond). Assuming 140 patients do not completely respond, we would need 350 patients on PPI therapy. Hence, 70 subjects will be randomized to receive PPI therapy and 30 randomized to placebo for each symptom group for a total N=500.
Analysis: Logistic regression.
Significance: This project will identify patients with laryngopharyngeal symptoms most likely to benefit from empiric PPI therapy. Until we have clarified which symptoms best respond and do not respond to therapy, we are bound to repeat the errors of the past. Finally, this project will further validate the SRQ for use in future trials.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00170001
|United States, Minnesota|
|Rochester, Minnesota, United States, 55905|
|Principal Investigator:||Yvonne Romero, M.D.||Mayo Clinic|