Evaluation of Acetylsalicylic Acid and Pantoprazole in Reducing Cardiovascular Events in Hospitalized Patients with Community-Acquired Pneumonia

The primary objective of this study is to evaluate whether the addition of **aspirin** to antibiotic therapy in patients with moderate to severe community-acquired **pneumonia** can reduce the incidence of acute coronary syndrome in hospitalized patients. This is clinically relevant as it addresses the potential for aspirin to mitigate cardiovascular complications, which are a significant concern in patients with pneumonia, potentially improving patient outcomes and reducing healthcare burdens.

Secondary objectives include: - Investigating the effects of adding aspirin on other cardiovascular events, length of hospital stay, mortality, adverse events, and cost-effectiveness. - In a subgroup of patients consenting to additional blood sampling and storage, the study aims to facilitate future research into the mechanisms of cardiovascular events in pneumonia patients and to explore the impact of aspirin on these mechanisms.

The clinical trial involves participants diagnosed with **community-acquired pneumonia** and aims to assess the impact of adding aspirin to antibiotic therapy on reducing the incidence of acute coronary syndrome. The study population includes both male and female subjects aged 40 years or older, who have been admitted to the hospital with moderate to severe pneumonia, as indicated by a CURB-65 score of 2 or higher or a PSI score of 3 or higher. The trial does not focus on a vulnerable population, and no specific lifestyle considerations such as diet or physical activity are highlighted. The sponsor has not provided information regarding the total number of participants in the study.

The clinical trial is designed to evaluate the efficacy of **acetylsalicylic acid** in reducing the incidence of acute coronary syndrome in patients with moderate to severe community-acquired **pneumonia**. This study is a randomized, double-blind, controlled trial with a duration of 180 days. Participants will be randomly assigned to receive either acetylsalicylic acid, **pantoprazole**, or a **placebo**. The trial will commence with a screening visit to confirm eligibility based on criteria such as age (40 years or older), clinical and radiological evidence of pneumonia, and hospital admission. The primary endpoint is the incidence of acute coronary syndrome up to day 180, with secondary endpoints including the incidence of major adverse cardiovascular events, bleeding complications, length of hospital stay, mortality, societal costs, and health-related quality of life.

Participants will be involved in the study for a maximum of 90 days of treatment, with follow-up assessments extending to 180 days. Study visits will include an initial screening visit, baseline assessments, periodic follow-up visits to monitor safety and efficacy, and an end-of-study visit to evaluate final outcomes. Conditions that may lead to early termination from the study include withdrawal of consent, adverse events, or non-compliance with the study protocol. The trial is categorized as a low-intervention study due to the established safety profile of acetylsalicylic acid, which is widely used for cardiovascular prevention. The trial is expected to conclude by April 2028, with recruitment starting in October 2023.

The clinical trial involves the administration of three different treatments, including a **placebo**, **pantoprazole**, and **acetylsalicylic acid**. The **placebo** is formulated as a tablet and is administered orally. It contains no active pharmaceutical ingredient and serves as a control to compare the effects of the experimental treatments. The placebo is administered with a maximum treatment period of 90 days, ensuring that participants receive a consistent regimen throughout the study duration.

**Pantoprazole**, marketed as Pantoprazol Teva 20 mg, is provided in the form of a gastro-resistant tablet. This medication is administered orally with a maximum daily dose of 20 mg and a total maximum dose of 1800 mg over the course of the study. The gastro-resistant formulation is designed to prevent the degradation of the active substance in the stomach, allowing for effective absorption in the intestine. The treatment period for pantoprazole is also set at 90 days.

**Acetylsalicylic acid**, known commercially as Acetylsalicylzuur Cardio Teva 80 mg, is dispensed as a dispersible tablet. This formulation allows for oral administration with a maximum daily dose of 80 mg and a total maximum dose of 7440 mg over the study period. The dispersible nature of the tablet facilitates ease of administration, particularly for patients who may have difficulty swallowing. The treatment duration for acetylsalicylic acid is consistent with the other treatments, set at 90 days.

All treatments are administered orally, and participant compliance is monitored throughout the trial to ensure adherence to the dosing schedule. The study aims to evaluate the efficacy of adding acetylsalicylic acid to standard antibiotic therapy in reducing the incidence of acute coronary syndrome in patients with moderate to severe community-acquired pneumonia. The use of a placebo and pantoprazole serves to control for potential confounding factors and to isolate the effects of acetylsalicylic acid in the study population.

Efficacy in this clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the incidence of an **acute coronary syndrome (ACS)** up to day 180. Secondary endpoints include the incidence of 4-point major adverse cardiovascular events (MACE), which encompasses nonfatal stroke, nonfatal myocardial infarction, cardiovascular death, and coronary revascularization, also measured up to day 180. Additional secondary endpoints are the incidence of major bleeding complications and clinically relevant non-major bleeding up to day 90, length of hospital stay, mortality at day 90 and day 180, societal costs up to day 180 measured with the IMCQ and IPCQ, and health-related quality of life assessed using the EQ-5D-5L instrument.