Primary carE PPi dEprescRibing Trial

NCT05629143 | Active Not Recruiting Phase 4

• 1 other identifier: S64556
• Study Type: interventional
• Target: 724
• Locations: 1 country
• Sites: 1

Brief Summary

Proton pump inibitors (PPIs) is a class of medications that reduce the acid secretion in the stomach. These medications are very effective to relieve symptoms of acid reflux for a well-identified group of diseases and conditions. Over the years, a major rise in use of these drugs has occurred. Convincing analyses reveal that a large share of this use occurs outside regular indications, at inappropriately elevated doses and prolonged treatment durations. Moreover, there are increasing concerns regarding potential adverse effects and the high cost associated with improper PPI use. Guidelines propose to reduce chronic use of PPIs, but to date this has not generated a reduction in their application in clinical practice. One reason is the occurrence of a period of 2 weeks of increased acid secretion, with recurrence of symptoms, when these drugs are stopped after already a few weeks of usage (rebound effect). The best strategy to overcome this period of increased acid secretion and symptoms has not been established. The PEPPER study will evaluate two different strategies to overcome the period of increased secretion when trying to interrupt chronic proton pump inhibitor therapy. The investigators will compare the success of stopping PPIs when these strategies are implemented, compared to a classical strategy of stopping after intermittent PPI intake. The strategies under evaluation are a period of non-daily intake of proton pump inhibitors (on-demand) before stopping, or the use of alternative methods to control gastric acidity and reflux (so-called alginates). The investigators will evaluate the success rate of stopping chronic PPIs treatment with these approaches, compared to an interruption with intake of antacids. Patients will be followed up for 1 year after interruption of PPIs, and the level of symptom control, quality of life and healthcare costs will be evaluated at intervals. The study will be conducted in patients from primary care practices with chronic PPIs intake outside of the established disease indications.

Conditions

Heartburn; Dyspepsia; Reflux

Keywords

proton pump inhibitor

Outcome Measures

Primary Outcomes (1)

• Succes of de-prescription strategy

  percentage of randomized patients achieving successful therapeutic outcome at the end of the follow up period in each treatment group

  15 months

Secondary Outcomes (3)

• Use of PPI

  15 months

• Treatment satisfaction

  15 months

• Willingness to continue with the current treatment

  15 months

Other Outcomes (9)

• Economic impact of PPI deprescribing

  15 months

• Predictor of success - Predictive value of the symptom pattern

  15 months

• Predictive value of demographic variables

  15 month

Study Arms (3)

Intermittent deprescribing strategy

OTHER

Classical approach for deprescribing of PPI based on Belgian Guidelines. In this study arm, the patients will keep the intake of their PPI but will decrease the use of PPI using a scheme where the PPI dose in reduced intermittently for one month. After one month in the intermittent deprescribing scheme, the patients will stop the use of PPI.

Procedure: de-prescription of PPI via intermittent scheme

On-demand deprescribing strategy

OTHER

In this study arm, the patients will keep the intake of their PPI but will decrease the use of PPI in an on-demand bases for one month. The patient will only take the PPI when strictly needed because of symptoms. After one month in the on-demand PPI use, the patients will stop the use of PPI.

Procedure: de-prescription of PPI via on-demand scheme

Replacement of PPI with alginate therapy

OTHER

In this study arm, the patient will stop the intake of the PPI band replace it with the use of an alginate for one month. After one month, the patient will stop the use of alginates.

Drug: Alginate

Interventions

de-prescription of PPI via intermittent scheme PROCEDURE

The patients will decrease their intake of PPIs via a de-prescription intermittent scheme. After one month, patients will stop their intake of PPI.

Intermittent deprescribing strategy

de-prescription of PPI via on-demand scheme PROCEDURE

The patients will decrease their intake of PPIs via a de-prescription on-demand scheme. After one month, patients will stop their intake of PPI.

On-demand deprescribing strategy

Alginate DRUG

The patients will stop their intake of PPIs and use alginate. After one month, patients will stop their intake of alginates.

Replacement of PPI with alginate therapy

Eligibility Criteria

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

You may qualify if:

• Eligible patients are those of either gender, above the age of 18, eligible to give informed consent
• Based on indication: Patients on long-term (\>12 weeks) chronic (daily) PPI use without therapy indication are eligible to participate.
• Based on dose:
• Patients on a "maintenance" PPI dose are eligible for randomization. Maintenance dose is 20 mg of omeprazole, esomeprazole or pantoprazole daily or 15 mg of lansoprazole daily or 10 mg of rabeprazole daily.
• Patients on a "healing" PPI dose (i.e. ≥40 mg esomeprazole, esomeprazole or pantoprazole or ≥30 mg of lansoprazole or ≥20 mg or rabeprazole daily) are also eligible, but need first to down-titrate their dose to "maintenance" dose before they can be considered for randomization.

You may not qualify if:

• Patients on short-term (\<12 weeks) PPI therapy.
• Patients not on chronic PPI use (less than daily intake)
• Patients with established long-term indication such as the presence of a grade C, D oesophagitis, a peptic ulcer, Barrett's oesophagus or Zollinger-Ellison syndrome.
• Patients with chronic use of Gaviscon® or similar drugs based on magaldrate such as Riopan® and Gastricalm® (i.e. more than once a week for the last 2 months).
• Patients with chronic use of NSAIDs (i.e. two or more weekly doses).
• Patients with a history of gastric or oesophageal surgery.
• Patients with a major oesophageal disease such as achalasia, oesophageal spasm, or oesophageal involvement in systemic disease such as scleroderma or dermatomyositis.
• Patients with drug abuse and/or alcohol abuse
• Women who are pregnant or lactating
• Patients not able to understand or be compliant with the study.

Sponsors & Collaborators

• Universitaire Ziekenhuizen KU Leuven: lead

Study Sites (1)

Jan Tack

Leuven, Vlaams Brabant, 3000, Belgium

Location

MeSH Terms

Conditions

Heartburn; Dyspepsia; Gastroesophageal Reflux

Interventions

Alginates

Condition Hierarchy (Ancestors)

Signs and Symptoms, Digestive; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Esophageal Motility Disorders; Deglutition Disorders; Esophageal Diseases; Gastrointestinal Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Polysaccharides; Carbohydrates

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Evaluation of de-prescription strategies for PPIs

Study Record Dates

• First Submitted: November 3, 2022
• First Posted: November 29, 2022
• Study Start: May 12, 2023
• Primary Completion: March 1, 2026
• Study Completion (Estimated): June 1, 2026
• Last Updated: January 31, 2025

Record last verified: 2025-01

Data Sharing

• IPD Sharing: Will not share

Locations

BE (1)