Primary carE PPi dEprescRibing Trial (PEPPER)

January 29, 2025 updated by: Universitaire Ziekenhuizen KU Leuven

Determining the Optimal Strategy for Stopping Chronic Proton Pump Inhibitor Therapy in Primary Care Patients: Impact of On-demand Use, Adjunctive Therapies and Antacids

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
724

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Belgium
    • Vlaams Brabant
      • Leuven, Vlaams Brabant, Belgium, 3000
        • Jan Tack

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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.

Exclusion Criteria:

  • 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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Intermittent deprescribing strategy
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
The patients will decrease their intake of PPIs via a de-prescription intermittent scheme. After one month, patients will stop their intake of PPI.
Other: On-demand deprescribing strategy
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
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.
Other: Replacement of PPI with alginate therapy
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
The patients will stop their intake of PPIs and use alginate. After one month, patients will stop their intake of alginates.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Succes of de-prescription strategy
Time Frame: 15 months
percentage of randomized patients achieving successful therapeutic outcome at the end of the follow up period in each treatment group
15 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Use of PPI
Time Frame: 15 months

Patient reported outcome The use of PPI will be reported by the patient at each study visit as adherence to the suggested treatment. As this information is considered as standard of care, this is the value that will be used for the analysis of this first key point that will be used for the assessment of the primary endpoint of the study.

During follow up, patients taking at least one dose of PPIs weekly will be consider as active PPI users, and therefore a failure to this key indicator (result "0"). If patients report to have used a dose PPI less than 3 times in a month, this subject will not be consider as clinical relevant users, and therefore the key indicator result is positive and "1".
15 months
Treatment satisfaction
Time Frame: 15 months
Patient reported outcome Scale title:treatment satisfaction scale Question to assess treatment satisfaction is: "How satisfied or dissatisfied are you with the control of your symptoms with the current treatment?" Minimum and maximum values: seven-point bipolar scale from 'Extremely Satisfied' (score 7) to 'Extremely Dissatisfied' (score 1) Higher scores mean: better outcome
15 months
Willingness to continue with the current treatment
Time Frame: 15 months
Patient reported outcome To assess willingness to continue to current treatment regimen, the following question will be used: "Would you be willing to continue the current treatment for the next month?"
15 months

Other Outcome Measures

Other Outcome Measures

For clinical trials, a planned measurement described in the protocol that is used to determine the effect of an intervention/treatment on participants. For observational studies, a measurement or observation that is used to describe patterns of diseases or traits, or associations with exposures, risk factors, or treatment. Types of outcome measures include primary outcome measure and secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Economic impact of PPI deprescribing
Time Frame: 15 months
Title: Health resource utilisation questionnaire Minimum and maximum values: yes or no questions (1 or 0) regarding use health resource use Higher scores mean: worst outcome as this is related to more expences due to health issues
15 months
Predictor of success - Predictive value of the symptom pattern
Time Frame: 15 months

Patient reported outcome questionnaire title:esophageal and gastric symptoms questionnaire Min and max values: varies based on the question to presence of a symptom: yes-no questions and the severity of symptoms with higher scores for more severe symptoms.

Higher scores means worst outcome as symptoms are more present and more severe.
15 months
Predictive value of demographic variables
Time Frame: 15 month
Demographic assessment with patients questionnaires
15 month
Predictive value of number of co-morbidities to stop PPIs use
Time Frame: 15 months
Co-morbidities assessment via GP via eCRF The investigator will evaluate if increased number of co-morbidities is a predictor for lower likelihood to succeed a the treatment to decrease the use of PPI.
15 months
Predictive value of number of previous failed attempts to stop PPIs use
Time Frame: 15 months
Assessment via eCRF via GP medical assessment The investigator will evaluate if the number of previous failed attempts to stop PPIs use is a predictor for lower likelihood to succeed a the treatment to decrease the use of PPI.
15 months
Predictive value of gastrin level
Time Frame: 15 months
Blood sample at baseline and after 1 year follow-up
15 months
Predictive value of the level of patients' motivation to stop PPIs use
Time Frame: 15 months
Patient reported outcome on motivation during the study title: Motivational visual analogue scale Max-min scores: 100-0 from "extremely motivated" to "no motivation" Higher scores: good outcome The investigator will evaluate if the level of motivation to stop PPIs use is a predictor for likelihood to succeed a the treatment to decrease the use of PPI.
15 months
Work productivity impact of PPI deprescribing
Time Frame: 15 months
title: Work productivity impact questionnaire (WPAI) Max-Min scores: yes/no questions (1/0) and number of hours worked per week (scores: 0 to 150) Higer scores= good outcome, as the patients feels good to work and be productive
15 months
Number of participants using rescue therapy
Time Frame: 15 months
Assessment via questionnaire in ePRO
15 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Universitaire Ziekenhuizen KU Leuven

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 12, 2023

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2026

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 1, 2026

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 3, 2022

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 16, 2022

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 29, 2022

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 29, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • S64556

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

no individual data sharing

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings