HeartburnPhase 4PEPPERNCT05629143

Primary carE PPi dEprescRibing Trial

A Phase 4 study testing de-prescription of PPI via intermittent scheme, de-prescription of PPI via on-demand scheme and Alginate in people with Heartburn and Dyspepsia, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heartburn, Dyspepsia, Reflux
What is being tested?: de-prescription of PPI via intermittent scheme, de-prescription of PPI via on-demand scheme and Alginate
Type of treatment: Surgery or procedure
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 724 participants
Where: 1 siteBelgium
Study dates: 12 May 2023to 1 Jun 2026
Phase: Phase 4
Are there results?: Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

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.

Who cannot join

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.

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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.

Trial locations and contacts

1 site in 1 country.

Belgium1 site

Jan Tack
Leuven, Vlaams Brabant, 3000

Other trials in Belgium

About this study

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

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
Being tested: de-prescription of PPI via intermittent scheme, de-prescription of PPI via on-demand scheme, Alginate
Keywords: proton pump inhibitor
Medical subject headings: Heartburn, Dyspepsia, Gastroesophageal Reflux

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

de-prescription of PPI via intermittent schemeProcedure or surgery
The patients will decrease their intake of PPIs via a de-prescription intermittent scheme. After one month, patients will stop their intake of PPI.
de-prescription of PPI via on-demand schemeProcedure or surgery
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.
AlginateDrug
The patients will stop their intake of PPIs and use alginate. After one month, patients will stop their intake of alginates.

Study groups in NCT05629143
Study group	Role	What they receive
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. Receives: 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. Receives: 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. Receives: Drug: Alginate

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 15 months

Secondary outcomes (3)

Use of PPI
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".
Measured: 15 months
Treatment satisfaction
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
Measured: 15 months
Willingness to continue with the current treatment
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?"
Measured: 15 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 May 20231 Jun 2026

First posted29 Nov 2022
Study start12 May 2023
Primary completion1 Mar 2026 (estimated)
Study completion1 Jun 2026 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HeartburnStudies of the same condition, open and under way.
More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Model description: Evaluation of de-prescription strategies for PPIs
Masking: None (open label)
Enrolment: 724 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05629143
Sponsor's protocol ID: S64556
Acronym: PEPPER
Status last verified: Jan 2025
First submitted: 3 Nov 2022
Last updated: 31 Jan 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No: no individual data sharing

Publications

Carbone F, Scheepers J, Van den Houte K, Laenen A, Tack J. Primary carE PPi dEprescRibing (PEPPER) trial: a protocol for determining the optimal strategy for stopping chronic proton pump inhibitor therapy in primary care patients. BMJ Open. 2026 Apr 17;16(4):e101266. doi: 10.1136/bmjopen-2025-101266.
PubMed 41997699

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Vonoprazan 10 mg Compared to Placebo for Relief of Episodic Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease Through 24 Weeks
Symptomatic Non-erosive Gastroesophageal Reflux Disease
Active, not recruitingPhase 3
Domperidone in Treating Patients With Gastrointestinal Disorders
Digestive System Disorder, Dyspepsia
RecruitingObservational study
A Study of the Safety of Vonoprazan Exposure in Pregnant Women and Their Offspring
Erosive Esophagitis, Heartburn
Enrolling by invitationObservational study
The Johns Hopkins Heartburn Center Registry
Gastroesophageal Reflux Disease, Barrett Esophagus
Not yet recruiting
Antireflux Surgery Without Preoperative Esophageal Manometry
GERD, Hiatal Hernia

All Heartburn trials

Study at a glance

From the registry record, last updated by the sponsor on 31 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Determining the Optimal Strategy for Stopping Chronic Proton Pump Inhibitor Therapy in Primary Care Patients: Impact of On-demand Use, Adjunctive Therapies and Antacids
ClinicalTrials.gov ID: NCT05629143
Acronym / sponsor ID: PEPPER / S64556
Conditions: Heartburn, Dyspepsia, Reflux
Keywords: proton pump inhibitor
Phase: Phase 4
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 724 participants (estimated)
Lead sponsor: Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
Study start: 12 May 2023 (actual)
Primary completion: 1 Mar 2026 (estimated)
Study completion: 1 Jun 2026 (estimated)
First posted: 29 Nov 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

The study will be conducted in patients from primary care practices with chronic PPIs intake outside of the established disease indications.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3
Model description: Evaluation of de-prescription strategies for PPIs

Arm	Type	Receives
Intermittent deprescribing strategy	Other	Procedure: de-prescription of PPI via intermittent schemeClassical 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.
On-demand deprescribing strategy	Other	Procedure: de-prescription of PPI via on-demand schemeIn 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.
Replacement of PPI with alginate therapy	Other	Drug: AlginateIn 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.

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

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:

Key exclusion criteria (10 listed)

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).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
de-prescription of PPI via intermittent schemeThe patients will decrease their intake of PPIs via a de-prescription intermittent scheme. After one month, patients will stop their intake of PPI.	Procedure or surgery	Intermittent deprescribing strategy
de-prescription of PPI via on-demand schemeThe patients will decrease their intake of PPIs via a de-prescription on-demand scheme. After one month, patients will stop their intake of PPI.	Procedure or surgery	On-demand deprescribing strategy
AlginateThe patients will stop their intake of PPIs and use alginate. After one month, patients will stop their intake of alginates.	Drug	Replacement of PPI with alginate therapy

Primary outcome

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

3 secondary outcomes

Use of PPI
Time frame: 15 months
Treatment satisfaction
Time frame: 15 months
Willingness to continue with the current treatment
Time frame: 15 months

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 31 Jan 2025.
Derived from this study: PubMed 41997699Carbone F, Scheepers J, Van den Houte K, Laenen A, Tack J. Primary carE PPi dEprescRibing (PEPPER) trial: a protocol for determining the optimal strategy for stopping chronic proton pump inhibitor therapy in primary care patients. BMJ Open. 2026 Apr 17;16(4):e101266. doi: 10.1136/bmjopen-2025-101266.
Individual participant dataSharing planned: No. no individual data sharing

Related trials for Heartburn

RecruitingPhase 3
A Study to Evaluate the Efficacy and Safety of Vonoprazan 10 mg Compared to Placebo for Relief of Episodic Heartburn in Participants With Symptomatic Non-Erosive Gastroesophageal Reflux Disease Through 24 Weeks
Symptomatic Non-erosive Gastroesophageal Reflux Disease
Active, not recruitingPhase 3
Domperidone in Treating Patients With Gastrointestinal Disorders
Digestive System Disorder, Dyspepsia
RecruitingObservational study
A Study of the Safety of Vonoprazan Exposure in Pregnant Women and Their Offspring
Erosive Esophagitis, Heartburn
Enrolling by invitationObservational study
The Johns Hopkins Heartburn Center Registry
Gastroesophageal Reflux Disease, Barrett Esophagus
Not yet recruiting
Antireflux Surgery Without Preoperative Esophageal Manometry
GERD, Hiatal Hernia

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 31 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Belgium. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Succes of de-prescription strategy (time frame: 15 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05629143, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 31 Jan 2025.