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PROGRESSive Withdrawal Esomeprazole and Acid-related Symptoms (PROGRESS)

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ClinicalTrials.gov Identifier: NCT02476097
Recruitment Status : Recruiting
First Posted : June 19, 2015
Last Update Posted : April 19, 2019
Sponsor:
Information provided by (Responsible Party):
Jules Desmeules, University Hospital, Geneva

Brief Summary:

Rebound acid hypersecretion (RAHS), defined as an increase in gastric acid secretion above pre-treatment levels after PPIs therapy is observed within two weeks after withdrawal of treatment and could theoretically lead to acid-related symptoms such as heartburn, acid regurgitation, or dyspepsia that might result in resumption of therapy. A plausible physiologic theory for the rebound phenomenon suggests that long-term, elevated gastric pH caused by blockage of the proton-pumps stimulates compensatory gastrin release. Interestingly, Reimer et al. demonstrated the occurrence of RAHS in healthy volunteers who had received eight weeks of esomperazole. The clinical symptoms occured in a different prevalence compared with placebo treated patients at ten weeks after withdrawal and until the end of the study (twelve weeks). Twenty to twenty-two percent of patients displayed symptoms ten or twelve weeks after having discontinued PPIs while they occured in 1.7-7% of placebo-treated patients. Efforts should be pursued to restrict PPI therapy use to patients likely to benefit from it.

In this context, we propose to investigate the benefit of a progressive decrease in doses of esomeprazole compared to a sudden discontinuation. This is a randomized, double-blind, placebo-controlled trial with 156 patients treated by esomeprazole 40mg since four weeks least, randomized to one week of placebo or one week of esomeprazole 20mg. We want to compare the prevalence of clinical gastrointestinal symptoms between patients with progressive discontinuation (one week of esomeprazole, 20mg, then discontinuation) or those with sudden discontinuation of esomeprazole 40mg.


Condition or disease Intervention/treatment Phase
Stomach Diseases Drug: Esomeprazole: Nexium® 20mg, Astra Zeneca Other: CYP2C19 phenotypical analysis Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Study of the Effect of PROGRESSive Withdrawal Esomeprazole of on Acid-related Symptoms, PROGRESS Study A Randomized, Placebo-controlled, Double Blinded Study
Study Start Date : June 2015
Estimated Primary Completion Date : December 2021
Estimated Study Completion Date : December 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Placebo Comparator: Sudden discontinuation
placebo for 7 days
Other: CYP2C19 phenotypical analysis
All patients included will undergo an assessment of the CYP2C19 activity by the administration of omeprazole 40mg and following measurement of omeprazole metabolic ratio respectively, once during the study.
Other Name: omeprazole 40mg

Drug: Placebo
Comparison of the prevalence of clinical symptoms of acid rebound, between patients with progressive (esomeprazole ) or sudden (placebo) discontinuation of Proton pump inhibitors.

Active Comparator: Progressive discontinuation
Esomeprazole: Nexium® 20mg, Astra Zeneca , for 7 days
Drug: Esomeprazole: Nexium® 20mg, Astra Zeneca
Comparison of the prevalence of clinical symptoms of acid rebound, between patients with progressive (esomeprazole ) or sudden (placebo) discontinuation of Proton pump inhibitors.
Other Name: Nexium®

Other: CYP2C19 phenotypical analysis
All patients included will undergo an assessment of the CYP2C19 activity by the administration of omeprazole 40mg and following measurement of omeprazole metabolic ratio respectively, once during the study.
Other Name: omeprazole 40mg




Primary Outcome Measures :
  1. The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 1. [ Time Frame: day 8 ]

    The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

    The investigators will modifiy the first question for the study. While, it is usually asked: " Are you taking prescription medication for any of the following stomach problems/symptoms:… " ; in the study, the investigators will ask : " Do you have any of the following stomach problems/symptoms : … ".

    With any of the 7 symptoms, the patient will be considered as symptomatic.


  2. The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 2. [ Time Frame: day 15 ]

    The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

    The investigators will modifiy the first question for the study. While, it is usually asked: " Are you taking prescription medication for any of the following stomach problems/symptoms:… " ; in the study, the investigators will ask : " Do you have any of the following stomach problems/symptoms : … ".

    With any of the 7 symptoms, the patient will be considered as symptomatic.


  3. The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 3. [ Time Frame: day 22 ]

    The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

    The investigators will modifiy the first question for the study. While, it is usually asked: " Are you taking prescription medication for any of the following stomach problems/symptoms:… " ; in the study, the investigators will ask : " Do you have any of the following stomach problems/symptoms : … ".

    With any of the 7 symptoms, the patient will be considered as symptomatic.


  4. The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 4. [ Time Frame: day 29 ]

    The five-item PASS test is a valid tool for the evaluation of persistent acid-related symptoms in patients receiving PPI therapy. It demonstrates good content validity, test-retest reliability, responsiveness and construct validity in both English and French forms. The PASS test is a simple, clinically applicable tool for the identification of patients with persistent acid-related symptoms during therapy and the assessment of their responses to a change in therapy.

    The investigators will modifiy the first question for the study. While, it is usually asked: " Are you taking prescription medication for any of the following stomach problems/symptoms:… " ; in the study, the investigators will ask : " Do you have any of the following stomach problems/symptoms : … ".

    With any of the 7 symptoms, the patient will be considered as symptomatic.



Secondary Outcome Measures :
  1. The intensity of the acid rebound symptoms [ Time Frame: day 8 ]

    The entire modified-PASS test will be evaluated with respect to patients' responses to the individual question; For each symptom, its severity will be measured and scored (minimum score 0: patient has no symptoms; maximum score 4: patient has symptoms requiring supplemental medications and affecting sleep, eating, drinking and daily activities).

    The overall score will represent the consequence of the rebound acid symptoms.


  2. The intensity of the acid rebound symptoms [ Time Frame: day 15 ]

    The entire modified-PASS test will be evaluated with respect to patients' responses to the individual question; For each symptom, its severity will be measured and scored (minimum score 0: patient has no symptoms; maximum score 4: patient has symptoms requiring supplemental medications and affecting sleep, eating, drinking and daily activities).

    The overall score will represent the consequence of the rebound acid symptoms.


  3. The intensity of the acid rebound symptoms [ Time Frame: day 22 ]

    The entire modified-PASS test will be evaluated with respect to patients' responses to the individual question; For each symptom, its severity will be measured and scored (minimum score 0: patient has no symptoms; maximum score 4: patient has symptoms requiring supplemental medications and affecting sleep, eating, drinking and daily activities).

    The overall score will represent the consequence of the rebound acid symptoms.


  4. The intensity of the acid rebound symptoms [ Time Frame: day 29 ]

    The entire modified-PASS test will be evaluated with respect to patients' responses to the individual question; For each symptom, its severity will be measured and scored (minimum score 0: patient has no symptoms; maximum score 4: patient has symptoms requiring supplemental medications and affecting sleep, eating, drinking and daily activities).

    The overall score will represent the consequence of the rebound acid symptoms.




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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Treatment by esomeprazole 40mg since 4 weeks or more
  • Esomeprazole withdrawal decided by the clinician
  • Male and female aged 18-90 years
  • Volunteers to participate to the study
  • Must understand and read French language
  • Must be able to give a written informed consent

Exclusion Criteria:

  • Impairment of cognitive status
  • Current indication to continue PPI treatment
  • History of erosive and ulcerative esophagitis, Barrett esophagus, Zollinger-Ellison syndrome
  • Short-term treatment of documented ulcer disease, as part of a combination regimen for Helicobacter pylori (HP) eradication
  • Prevention of ulcers due to non-steroidal anti-inflammatory drugs.
  • Hepatic impairment (TP<60%)
  • Hypersensitivity to omeprazole (CYP2C19 activity) or esomeprazole
  • Current pregnancy or current breastfeeding

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02476097


Contacts
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Contact: Jules Desmeules, Pr 41(0)22 23 05 53 87 jules.desmeules@hcuge.ch

Locations
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Switzerland
Service de de médecine interne et de rehabilitation, Beau-séjour, HUG Recruiting
Genève, Switzerland
Contact: Jules Desmeules, Pr    41(0)22 23 05 53 87      
Principal Investigator: Jules Desmeules, Pr         
Service de réadaptation de l'appareil locomoteur Clinique romande de réadaptation, Sion Recruiting
Sion, Switzerland
Contact: Lucien Roulet, Pharm D       lucien.roulet@hopitalvs.ch   
Sponsors and Collaborators
Jules Desmeules

Publications of Results:
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Responsible Party: Jules Desmeules, Professor, University Hospital, Geneva
ClinicalTrials.gov Identifier: NCT02476097     History of Changes
Other Study ID Numbers: 15-003
First Posted: June 19, 2015    Key Record Dates
Last Update Posted: April 19, 2019
Last Verified: April 2019

Keywords provided by Jules Desmeules, University Hospital, Geneva:
esomeprazole randomized study
proton pump inhibitor
gastric acid rebound
randomized study
esomeprazole

Additional relevant MeSH terms:
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Stomach Diseases
Gastrointestinal Diseases
Digestive System Diseases
Omeprazole
Esomeprazole
Proton Pump Inhibitors
Anti-Ulcer Agents
Gastrointestinal Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action