Clinical trial NCT02476097: PROGRESSive Withdrawal Esomeprazole and Acid-related Symptoms
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Stomach Diseases
Keywords: esomeprazole randomized study
proton pump inhibitor
gastric acid rebound
randomized study
esomeprazole
Lead sponsor: University Hospital, Geneva
Sponsor class: OTHER
First posted: 2015-06-19
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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

Primary outcomes:
measure: The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 1.
timeFrame: day 8
measure: The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 2.
timeFrame: day 15
measure: The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 3.
timeFrame: day 22
measure: The proportions of patients answering "yes" to the clinical gastrointestinal symptoms questions were comparable at visit 4.
timeFrame: day 29
Secondary outcomes:
measure: The intensity of the acid rebound symptoms
timeFrame: day 8
measure: The intensity of the acid rebound symptoms
timeFrame: day 15
measure: The intensity of the acid rebound symptoms
timeFrame: day 22
measure: The intensity of the acid rebound symptoms
timeFrame: day 29
Other outcomes:
Locations:
city: Genève
country: Switzerland
facility: Service de de médecine interne et de rehabilitation, Beau-séjour, HUG
city: Sion
country: Switzerland
facility: Service de réadaptation de l'appareil locomoteur Clinique romande de réadaptation, Sion
Study officials:
References:
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.
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.
citation: 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.