Determining the optimal strategy for stopping chronic proton pump inhibitor therapy in primary care patients: impact of on-demand use, adjustment of therapy or discontinuation.

The primary objective of this study is to determine the optimal **deprescribing** strategy for chronic **proton pump inhibitor** (PPI) therapy in primary care patients who are using PPIs without a clear long-term indication. The study will assess the success rate of two novel approaches: (A) on-demand PPI use and (B) replacement of PPI therapy with an alginate formulation. These will be compared against the standard approach of gradually decreasing the PPI dose through fixed intermittent intake (C). The hypothesis is that the new strategies, A and B, will demonstrate superior efficacy compared to the standard approach C, and that strategy A will not be inferior to strategy B. This is clinically relevant as it addresses the need for effective PPI deprescribing strategies, potentially reducing unnecessary medication use and associated risks.

Secondary objectives include evaluating various parameters to provide insights into the time-course of success or failure of PPI deprescribing strategies. This information is crucial for understanding the dynamics of PPI withdrawal and optimizing patient outcomes.

The clinical trial involves a study population comprising **adults older than 18 years**, including both **males and females**. Participants are individuals who have been on long-term, chronic daily use of proton pump inhibitors (PPIs) for more than 12 weeks without a specific therapeutic indication. The trial does not include a vulnerable population. The sponsor has not provided information regarding the total number of participants. The selection criteria focus on individuals with conditions such as **functional dyspepsia**, heartburn, and reflux, who are currently using PPIs without an established need for long-term use. Lifestyle factors such as diet, physical activity, or habits are not specified in the available data. The trial aims to evaluate different de-prescribing strategies for PPIs, comparing on-demand use and replacement with an alginate formulation against the standard gradual dose reduction approach.

The clinical trial is designed to evaluate the optimal strategy for discontinuing chronic proton pump inhibitor (PPI) therapy in patients without a long-term indication for such treatment. This study employs a **randomized**, **double-blind**, and **controlled** methodology to ensure the reliability and validity of the results. The trial will compare three approaches: on-demand PPI use, replacement with an alginate formulation, and a gradual decrease of PPI dose through fixed intermittent intake. The trial is expected to last until August 29, 2025, with recruitment having started on April 28, 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (adults over 18) and chronic PPI use without a therapy indication. Follow-up visits will be scheduled to monitor the therapeutic outcomes, including PPI discontinuation, treatment satisfaction, and willingness to continue with the treatment. The primary endpoint is the percentage of patients achieving a successful therapeutic outcome by the end of the follow-up period. Secondary endpoints include the evaluation of key indicators at each visit and the percentage of weeks without PPI use during the follow-up.

The expected length of participant involvement is up to 31 days, with a maximum daily dose of 8 units and a total dose not exceeding 248 units. Conditions that may lead to early termination from the study include non-compliance with the study protocol or adverse events that compromise participant safety. The trial is categorized as low-intervention, with minimal additional risks compared to normal clinical practice, and aims to introduce new de-prescription strategies and guidelines for a widely used medication in Belgium.

The clinical trial involves the administration of several **experimental medications** and a comparator treatment. The first experimental medication is **Maalox Antacid® 200 mg/400 mg** in the form of **chewable tablets**. This formulation contains the active substances **aluminium oxide, hydrated** and **magnesium hydroxide**. The medication is administered orally, with a maximum daily dose of 8 units and a total maximum dose of 248 units over a treatment period of 31 days. The product is manufactured by Opella Healthcare Belgium, operating under the trade name Sanofi Belgium.

The second experimental medication is **Maalox Antacid® 230 mg/400 mg** as an **oral suspension**. This formulation also contains **aluminium oxide** and **magnesium hydroxide** as active substances. The administration route is oral, with the same dosing schedule as the chewable tablet form, allowing for a maximum of 8 units per day and a total of 248 units over 31 days. This product is also produced by Opella Healthcare Belgium.

The third experimental medication is **Maalox Antacid® Citroen 230 mg/400 mg** per 4.3 ml, available as an **oral suspension**. It contains **aluminium oxide, hydrated**, **aluminium oxide**, and **magnesium hydroxide**. The administration is oral, with a dosing schedule identical to the previous formulations, permitting up to 8 units daily and a total of 248 units over the course of 31 days. This product is manufactured by Opella Healthcare Belgium.

The fourth experimental medication is **Maalox Antacid® Suikervrij Citroen 200 mg/400 mg** in the form of **chewable tablets**. The active substances are **aluminium oxide, hydrated** and **magnesium hydroxide**. The administration is oral, with a maximum daily dose of 8 units and a total maximum dose of 248 units over a 31-day treatment period. This product is also produced by Opella Healthcare Belgium.

The comparator treatment in the study is **Gaviscon Antizuur - Antireflux Unidose 500mg/213mg/325mg**, provided as an **oral suspension in sachet** form. This formulation contains the active substances **sodium hydrogen carbonate**, **calcium carbonate**, and **sodium alginate**. The administration route is oral, with a maximum daily dose of 8 units and a total maximum dose of 248 units over a treatment period of 31 days. This product is manufactured by Reckitt Benckiser Healthcare (Belgium) SA/NV.

Efficacy in this clinical trial will be assessed by evaluating the success rate of different de-prescribing strategies for chronic proton pump inhibitor (PPI) therapy in patients without an established indication for long-term use. The primary endpoint is the percentage of randomized patients achieving a successful therapeutic outcome at the end of the follow-up period in each treatment group. A successful therapeutic outcome is determined by the sum of three predefined key points reported by the patient: the use of PPI, treatment satisfaction, and willingness to continue with the treatment.

Secondary endpoints include the evaluation of each key indicator for therapeutic success at each study visit, the percentage of successful therapeutic outcomes, and the percentage of weeks during the follow-up period in which patients did not use PPI. These assessments will be conducted throughout the trial to compare the efficacy of on-demand PPI use, replacement of PPI therapy with an **alginate** formulation, and the classical approach of gradual PPI dose reduction through fixed intermittent intake.