Evaluation of Acetylsalicylic Acid in Reducing Mortality in Elderly Patients with Acute Pneumonia: A Multicenter, Double-Blind, Randomized, Placebo-Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of aspirin on all-cause mortality after acute pneumonia at 90 days (D90) following randomization. This is clinically relevant as it aims to determine whether aspirin can reduce mortality rates in elderly patients suffering from acute pneumonia, potentially offering a therapeutic benefit in this vulnerable population.

Secondary objectives include assessing the efficacy of aspirin (100 mg/day for 90 days) on various clinical outcomes:

• All-cause mortality at D30 and D120.
• Cardiovascular (CV) mortality at D30, D90, and D120.
• Incidence of CV events, including myocardial infarction, stroke, acute heart failure, new atrial fibrillation, pulmonary embolism, CV death, and sudden death within 30, 90, and 120 days of randomization.
• Length of stay in intensive care or resuscitation unit within 90 days of randomization.
• Unscheduled rehospitalization within 30 and 90 days of randomization, excluding follow-up care and rehabilitation units and long-term care units.
• Length of first hospital stay, excluding follow-up care and rehabilitation units and long-term care units.
• Dependence at D90.
• Overall survival at D120.
• CV event-free survival at D120.
• All primary and secondary clinical judgments in various subgroups.
• Tolerability of aspirin.

The clinical trial involves participants diagnosed with **acute pneumonia**, with a focus on evaluating the efficacy of aspirin on all-cause mortality at 90 days post-randomization. The study population includes both male and female subjects aged 75 years and older. Participants are required to have a clinical diagnosis of acute pneumonia, presumed to be of bacterial or viral origin, and must exhibit at least two specific symptoms such as cough, purulent expectoration, thoracic pain, dyspnea or tachypnea, and abnormal body temperature. Additionally, participants must have been hospitalized for a minimum of 48 hours, with the onset of clinical signs occurring within the last seven days, and a new radiological infiltrate documented by X-ray, ultrasound, or CT scan. The trial includes a vulnerable population, but the total number of participants is not provided by the sponsor. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **aspirin** on all-cause mortality in elderly patients with **acute pneumonia**. This is a multicenter, double-blind, randomized, placebo-controlled trial. The trial will involve participants aged 75 years and older who have a clinical diagnosis of acute pneumonia, presumed to be of bacterial or viral origin, and meet specific inclusion criteria. The trial is expected to commence recruitment in February 2025 and conclude by June 2028, with a maximum treatment period of 90 days for each participant.

Participants will be randomly assigned to receive either the test product, **ACIDE ACETYLSALICYLIQUE PANPHARMA** 500 mg, or a placebo. The test product will be administered as a solution for injection, while the placebo will be a non-active comparator. The trial will also include a control group receiving **CHLORURE DE SODIUM 0.9% VIAFLO** as a solution for infusion. The primary endpoint is all-cause mortality at 90 days post-randomization, with secondary endpoints including cardiovascular mortality, occurrence of cardiovascular events, and frequency of major bleeding events.

The sequence of study visits includes an initial screening visit to confirm eligibility, followed by randomization and baseline assessments. Participants will undergo regular follow-up visits at 30, 90, and 120 days post-randomization to monitor efficacy and safety outcomes. The end-of-study visit will occur at 120 days or upon early termination. The expected length of participant involvement is up to 120 days, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance.

Key elements of the research methodology include the use of a double-blind design to minimize bias, randomization to ensure equal distribution of confounding factors, and the inclusion of a placebo group to provide a robust comparison. The trial will adhere to ethical guidelines, with informed consent obtained from all participants or their representatives. The study aims to provide valuable insights into the potential benefits of aspirin in reducing mortality and improving outcomes in elderly patients with acute pneumonia.

The clinical trial involves the administration of **ACIDE ACETYLSALICYLIQUE PANPHARMA 500 mg**, a **poudre pour solution injectable**. The active substance in this experimental medication is **D,L-lysine acetylsalicylate**. It is provided in the form of a **solution for injection** and is administered via **intravenous use**. The maximum daily dose is 100 mg, with a total maximum dose of 9000 mg over a treatment period of up to 90 days. The medication is manufactured by PANPHARMA and is not a pediatric formulation.

Another treatment used in the study is **CHLORURE DE SODIUM 0.9% VIAFLO**, a **solution pour perfusion**. The active substance is **sodium chloride**, and it is also administered intravenously. The solution for infusion has a maximum daily dose of 100 ml and a total maximum dose of 9000 ml over a 90-day period. This product is manufactured by BAXTER SAS and serves as a comparator treatment in the trial.

The study also includes the administration of **ASPIRINE PROTECT 100 mg**, a **comprimé gastro-resistant**. The active substance is **acetylsalicylic acid**, commonly known as aspirin. This medication is provided in the form of a **gastro-resistant tablet** and is administered orally. The maximum daily dose is 100 mg, with a total maximum dose of 9000 mg over a 90-day treatment period. The product is manufactured by BAYER HEALTHCARE and is used as a test treatment in the trial.

A **placebo** is also utilized in the trial, referred to as **Placebo d'acide acétylsalicylique**. This placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators know which treatment is being administered. The placebo does not contain any active substance and is used to compare the effects of the experimental treatments against a non-active control.

The efficacy of aspirin in the clinical trial titled "ASPAPY - Aspirin in acute pneumonia in the elderly: a multicenter, double-blind, randomized, placebo-controlled trial" will be assessed primarily by evaluating **all-cause mortality** at 90 days (D90) post-randomization. Secondary efficacy endpoints include all-cause mortality at 30 days (D30) and 120 days (D120), cardiovascular (CV) mortality at D30, D90, and D120, and the occurrence of CV events such as myocardial infarction, stroke, heart failure, new atrial fibrillation, pulmonary embolism, CV death, and sudden death within 30, 90, and 120 days of randomization. Additional secondary endpoints involve the number of days spent in intensive care or resuscitation units within 30 and 90 days, the occurrence of re-hospitalization within 30 and 90 days, and the duration of the first hospitalization excluding follow-up care, rehabilitation, and long-term care units.

Further assessments will include the proportion of newly institutionalized patients at D90, the proportion of patients with a decrease of ≥1 point on the activity of daily living (ADL) scale between pre-randomization status and D90, and the time to death from any cause, end of study (D120), or date of last follow-up, whichever occurs first. The time to CV event, death, end of study (D120), or date of last follow-up will also be evaluated. Tolerance will be assessed by the frequency of major bleeding events (BARC classification >2) and any severity of bleeding events within 30, 90, and 120 days of randomization. These efficacy parameters will be collected and analyzed at specified time points to determine the impact of aspirin on the specified outcomes in the elderly population with acute pneumonia.