Clinical trial NCT05629143: Primary carE PPi dEprescRibing Trial
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE4
Conditions: Heartburn
Dyspepsia
Reflux
Keywords: proton pump inhibitor
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
First posted: 2022-11-29
Enrollment: 724
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Evaluation of de-prescription strategies for PPIs
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Succes of de-prescription strategy
timeFrame: 15 months
Secondary outcomes:
measure: Use of PPI
timeFrame: 15 months
measure: Treatment satisfaction
timeFrame: 15 months
measure: Willingness to continue with the current treatment
timeFrame: 15 months
Other outcomes:
measure: Economic impact of PPI deprescribing
timeFrame: 15 months
measure: Predictor of success - Predictive value of the symptom pattern
timeFrame: 15 months
measure: Predictive value of demographic variables
timeFrame: 15 month
measure: Predictive value of number of co-morbidities to stop PPIs use
timeFrame: 15 months
measure: Predictive value of number of previous failed attempts to stop PPIs use
timeFrame: 15 months
measure: Predictive value of gastrin level
timeFrame: 15 months
measure: Predictive value of the level of patients' motivation to stop PPIs use
timeFrame: 15 months
measure: Work productivity impact of PPI deprescribing
timeFrame: 15 months
measure: Number of participants using rescue therapy
timeFrame: 15 months
Locations:
city: Leuven
country: Belgium
facility: Jan Tack
state: Vlaams Brabant
Study officials:
References: