Ignite Creation Date:
2024-05-06 @ 10:33 AM
Last Modification Date:
2024-10-26 @ 12:31 PM
Study NCT ID:
NCT03282084
Status:
WITHDRAWN
Last Update Posted:
2019-04-02
First Post:
2017-06-09
Brief Title:
A Prospective Observational Study of the PPI Non-responder
Sponsor:
Dartmouth-Hitchcock Medical Center
Organization:
Dartmouth-Hitchcock Medical Center
Study Overview
Official Title:
A Prospective Observational Study of the PPI Non-responder
Status:
WITHDRAWN
Status Verified Date:
2019-03
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
insufficient funding
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Gastroesophageal reflux disease GERD is a common chronic condition affecting approximately 20 of the American adult population Proton pump inhibitors PPIs are now the mainstay of medical therapy for symptoms of GERD Despite their efficacy several studies have shown that a significant proportion of GERD patients are either partial or non-responders to PPI therapy defined as symptoms of heartburn andor regurgitation not relieved by either a standard or double dose of a PPI during a minimum trial of 8 weeks If GERD symptoms persist further testing is required This study will mirror the real world setting to assess the value of published guidelines which recommend specific testing and treatment
Detailed Description:
Gastroesophageal reflux disease GERD is a common chronic condition affecting approximately 20 of the American adult population Gastroesophageal reflux disease is characterized by a number of symptoms the 2 most common being frequent heartburn and acid regurgitation Untreated or undertreated gastroesophageal reflux GER can lead to complications including esophageal erosions strictures esophageal adenocarcinoma and impaired quality of life
Proton pump inhibitors PPIs are now the mainstay of medical therapy for symptoms of GERD Despite their efficacy several studies have shown that a significant proportion of GERD patients are either partial or non-responders to PPI therapy defined as symptoms of heartburn andor regurgitation not relieved by either a standard or double dose of a PPI during a minimum trial of 8 weeks A review of 19 studies looking at GERD patients treated with PPIs found an overall prevalence of partial and non-responders of up to 45 in observational studies Non-randomized studies revealed a prevalence of 17 when defined as persisting troublesome heartburn and 28 when defined as troublesome regurgitation while randomized studies revealed prevalence rates of 32 and 28 respectively
Current guidelines recommend an 8-week trial of a daily PPI for the treatment of symptoms thought secondary to GERD However if GERD symptoms persist despite taking the PPI correctly then testing is required National guidelines recommend that patients with GERD symptoms who have failed empiric therapy with a PPI undergo upper endoscopy EGD This recommendation is based on data showing that the PPI non-responsive patient may have a disorder eg peptic ulcer disease dyspepsia eosinophilic esophagitis cancer that can only be identified by EGD During upper endoscopy a 48-hour wireless pH capsule can be placed to measure acid reflux into the distal esophagus This recommended practice has been shown to be cost effective If the 48 hour wireless pH capsule study documents pathologic acid reflux then the diagnosis of acid reflux is confirmed and the patient should be restarted on a PPI with appropriate counseling regarding how to take a PPI properly Switching the patient to an alternative PPI is a reasonable strategy as some patients respond better to one PPI than another In addition during this index endoscopy biopsies of the esophagus should be taken to rule out eosinophilic esophagitis
Some patients in clinical practice have previously undergone testing due to their GERD symptoms In patients with proven GERD eg prior EGD with LA Grade B-D esophagitis known Barretts esophagus prior positive pH tests either on or off PPI therapy who continue to have GERD symptoms on a daily PPI guidelines recommend that impedance pH-testing be performed on daily PPI therapy Guidelines do not recommend testing on bid PPI therapy since most patients with GERD do not require twice-daily PPI therapy In this patient population the PPI non-responder with proven GERD impedance-pH testing is preferable to 48-hour wireless pH capsule testing as non-acid reflux can be detected as well To be cost effective and to reduce the number of unnecessary EGDs if upper endoscopy was recently performed then impedance-pH testing can be performed after accurate localization of the lower esophageal sphincter using high resolution esophageal manometry HREM If the impedance-pH test is negative normal on daily PPI therapy demonstrating that acid reflux is controlled then a second diagnosis should to be considered eg functional dyspepsia gastroparesis an esophageal motility disorder If impedance-pH monitoring demonstrates abnormal acid reflux on daily PPI therapy then guidelines recommend that the PPI dose should be increased to twice daily and symptoms reassessed at 8 weeks
The clinical treatment pathways outlined above are based on national guidelines and are promoted as standards of care However despite the fact that these guidelines recommend distinct diagnostic pathways for patients who are non-responsive to PPIs there is little real-world data to support these guidelines and no information about the outcomes of these patients who are treated using these diagnostic pathways The simple goal of this study is to identify the PPI non-responder patient with GERD symptoms and identify and quantify the type number and outcomes of diagnostic tests recommended by national guidelines
Proton pump inhibitors PPIs are now the mainstay of medical therapy for symptoms of GERD Despite their efficacy several studies have shown that a significant proportion of GERD patients are either partial or non-responders to PPI therapy defined as symptoms of heartburn andor regurgitation not relieved by either a standard or double dose of a PPI during a minimum trial of 8 weeks A review of 19 studies looking at GERD patients treated with PPIs found an overall prevalence of partial and non-responders of up to 45 in observational studies Non-randomized studies revealed a prevalence of 17 when defined as persisting troublesome heartburn and 28 when defined as troublesome regurgitation while randomized studies revealed prevalence rates of 32 and 28 respectively
Current guidelines recommend an 8-week trial of a daily PPI for the treatment of symptoms thought secondary to GERD However if GERD symptoms persist despite taking the PPI correctly then testing is required National guidelines recommend that patients with GERD symptoms who have failed empiric therapy with a PPI undergo upper endoscopy EGD This recommendation is based on data showing that the PPI non-responsive patient may have a disorder eg peptic ulcer disease dyspepsia eosinophilic esophagitis cancer that can only be identified by EGD During upper endoscopy a 48-hour wireless pH capsule can be placed to measure acid reflux into the distal esophagus This recommended practice has been shown to be cost effective If the 48 hour wireless pH capsule study documents pathologic acid reflux then the diagnosis of acid reflux is confirmed and the patient should be restarted on a PPI with appropriate counseling regarding how to take a PPI properly Switching the patient to an alternative PPI is a reasonable strategy as some patients respond better to one PPI than another In addition during this index endoscopy biopsies of the esophagus should be taken to rule out eosinophilic esophagitis
Some patients in clinical practice have previously undergone testing due to their GERD symptoms In patients with proven GERD eg prior EGD with LA Grade B-D esophagitis known Barretts esophagus prior positive pH tests either on or off PPI therapy who continue to have GERD symptoms on a daily PPI guidelines recommend that impedance pH-testing be performed on daily PPI therapy Guidelines do not recommend testing on bid PPI therapy since most patients with GERD do not require twice-daily PPI therapy In this patient population the PPI non-responder with proven GERD impedance-pH testing is preferable to 48-hour wireless pH capsule testing as non-acid reflux can be detected as well To be cost effective and to reduce the number of unnecessary EGDs if upper endoscopy was recently performed then impedance-pH testing can be performed after accurate localization of the lower esophageal sphincter using high resolution esophageal manometry HREM If the impedance-pH test is negative normal on daily PPI therapy demonstrating that acid reflux is controlled then a second diagnosis should to be considered eg functional dyspepsia gastroparesis an esophageal motility disorder If impedance-pH monitoring demonstrates abnormal acid reflux on daily PPI therapy then guidelines recommend that the PPI dose should be increased to twice daily and symptoms reassessed at 8 weeks
The clinical treatment pathways outlined above are based on national guidelines and are promoted as standards of care However despite the fact that these guidelines recommend distinct diagnostic pathways for patients who are non-responsive to PPIs there is little real-world data to support these guidelines and no information about the outcomes of these patients who are treated using these diagnostic pathways The simple goal of this study is to identify the PPI non-responder patient with GERD symptoms and identify and quantify the type number and outcomes of diagnostic tests recommended by national guidelines
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None