PROGRESSive Withdrawal Esomeprazole and Acid-related Symptoms

Victoria Rollason

Status and phase: Active, not recruiting; Phase 4

Conditions: Stomach Diseases

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

Study type: Interventional

Funder types: Other

Identifiers

NCT02476097

15-003

Details and patient eligibility

About

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.

Enrollment: 58 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

---

58 participants in 2 patient groups, including a placebo group

Sudden discontinuation

Placebo Comparator group

Description:

placebo for 7 days

Treatment:

Drug: Placebo

Other: CYP2C19 phenotypical analysis

Progressive discontinuation

Active Comparator group

Description:

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

Treatment:

Drug: Esomeprazole: Nexium® 20mg, Astra Zeneca

Other: CYP2C19 phenotypical analysis