PROGRESSive Withdrawal Esomeprazole and Acid-related Symptoms

Stomach Diseases Clinical Trial

— PROGRESS  

Official title:

Study of the Effect of PROGRESSive Withdrawal Esomeprazole of on Acid-related Symptoms, PROGRESS Study A Randomized, Placebo-controlled, Double Blinded Study

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02476097
• Other study ID #: 15-003
• Status: Active, not recruiting
• Phase: Phase 4
• Start date: June 2015
• Est. completion date: December 2023

Study information

• Verified date: May 2023
• Source: University Hospital, Geneva
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 58
• Est. completion date: December 2023
• Est. primary completion date: December 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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

Related Conditions & MeSH terms

• Stomach Diseases

Intervention

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:
• 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.

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.

Locations

Country	Name	City	State
Switzerland	Service de de médecine interne et de rehabilitation, Beau-séjour, HUG	Genève
Switzerland	Service de réadaptation de l'appareil locomoteur Clinique romande de réadaptation, Sion	Sion

Sponsors (1)

Lead Sponsor	Collaborator
Victoria Rollason

Country where clinical trial is conducted

Switzerland, 

References & Publications (3)

Bjornsson E, Abrahamsson H, Simren M, Mattsson N, Jensen C, Agerforz P, Kilander A. Discontinuation of proton pump inhibitors in patients on long-term therapy: a double-blind, placebo-controlled trial. Aliment Pharmacol Ther. 2006 Sep 15;24(6):945-54. doi — View Citation

Katz MH. Failing the acid test: benefits of proton pump inhibitors may not justify the risks for many users. Arch Intern Med. 2010 May 10;170(9):747-8. doi: 10.1001/archinternmed.2010.64. No abstract available. — View Citation

Waldum HL, Arnestad JS, Brenna E, Eide I, Syversen U, Sandvik AK. Marked increase in gastric acid secretory capacity after omeprazole treatment. Gut. 1996 Nov;39(5):649-53. doi: 10.1136/gut.39.5.649. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 1.	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.	day 8
Primary	The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 2.	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.	day 15
Primary	The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 3.	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.	day 22
Primary	The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 4.	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.	day 29
Secondary	The intensity of the acid rebound symptoms	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.	day 8
Secondary	The intensity of the acid rebound symptoms	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.	day 15
Secondary	The intensity of the acid rebound symptoms	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.	day 22
Secondary	The intensity of the acid rebound symptoms	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.	day 29