PROGRESSive Withdrawal Esomeprazole and Acid-related Symptoms

NCT02476097 | Unknown Phase 4

• 1 other identifier: 15-003
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 2

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.

Conditions

Stomach Diseases

Keywords

esomeprazole randomized study; proton pump inhibitor; gastric acid rebound; randomized study; esomeprazole

Outcome Measures

Primary Outcomes (4)

• 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

• 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

• 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

• 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 Outcomes (4)

• The intensity of the acid rebound symptoms

  day 8

• The intensity of the acid rebound symptoms

  day 15

• The intensity of the acid rebound symptoms

  day 22

• The intensity of the acid rebound symptoms

  day 29

Study Arms (2)

Sudden discontinuation

PLACEBO COMPARATOR

placebo for 7 days

Other: CYP2C19 phenotypical analysis; Drug: Placebo

Progressive discontinuation

ACTIVE COMPARATOR

Esomeprazole: Nexium® 20mg, Astra Zeneca , for 7 days

Drug: Esomeprazole: Nexium® 20mg, Astra Zeneca; Other: CYP2C19 phenotypical analysis

Interventions

Esomeprazole: Nexium® 20mg, Astra Zeneca DRUG

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

Also known as: Nexium®

Progressive discontinuation

CYP2C19 phenotypical analysis OTHER

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.

Also known as: omeprazole 40mg

Progressive discontinuation; Sudden discontinuation

Placebo DRUG

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

Sudden discontinuation

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Victoria Rollason: lead

Study Sites (2)

Service de de médecine interne et de rehabilitation, Beau-séjour, HUG

Geneva, Switzerland

Location

Service de réadaptation de l'appareil locomoteur Clinique romande de réadaptation, Sion

Sion, Switzerland

Location

Related Publications (3)

• 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.

  PMID: 20458079 RESULT

• 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.

  PMID: 9026477 RESULT

• 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: 10.1111/j.1365-2036.2006.03084.x.

  PMID: 16948806 RESULT

MeSH Terms

Conditions

Stomach Diseases

Interventions

Esomeprazole; Omeprazole

Condition Hierarchy (Ancestors)

Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

2-Pyridinylmethylsulfinylbenzimidazoles; Sulfoxides; Sulfur Compounds; Organic Chemicals; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Benzimidazoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Dr

Study Record Dates

• First Submitted: June 15, 2015
• First Posted: June 19, 2015
• Study Start: June 1, 2015
• Primary Completion: December 1, 2023
• Study Completion: December 1, 2023
• Last Updated: May 26, 2023

Record last verified: 2023-05

Locations

CH (2)