Comparison of Oral Amoxicillin Versus Outpatient Parenteral Antibiotic Therapy in Patients with Infective Endocarditis: A Non-Inferiority Study

The primary objective of this study is to demonstrate the **non-inferiority** of outpatient oral antibiotic therapy compared to outpatient parenteral antibiotic treatment (OPAT) in patients with **infective endocarditis**. This is clinically relevant as it may offer a more convenient and potentially cost-effective treatment option without compromising efficacy.

Secondary objectives include:

• Evaluating the quality of life and patient satisfaction, which are important for understanding the broader impact of treatment on patients' daily lives.
• Assessing the costs of both interventions through a pharmaco-economic sub-study, providing insights into the economic implications of each treatment modality.
• Evaluating complications related to parenteral and oral administration of antibiotics, such as antibiotic or catheter-related adverse events (e.g., phlebitis and line-related bloodstream infections) and superinfections (e.g., **Clostridium difficile** diarrhea), to ensure the safety profile of the treatments.

The clinical trial focuses on **infective endocarditis** and aims to evaluate the non-inferiority of outpatient oral antibiotic therapy compared to outpatient parenteral antibiotic treatment. The study population includes both male and female participants aged 18 years and older. Participants are selected based on specific criteria, including having left-sided native or prosthetic infective endocarditis caused by non-resistant microorganisms, such as non-resistant streptococci, Enterococcus faecalis, and Staphylococcus aureus. The trial involves individuals who have received at least 10 days of appropriate parenteral antibiotic treatment, with a minimum of one week post-valve surgery. Participants must have a body temperature below 38.0°C for more than two days, a significant reduction in C-reactive protein levels, and a white blood cell count below 15 × 10(9)/L. Echocardiography is required to confirm the absence of abscess formation. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the **non-inferiority** of outpatient oral antibiotic therapy compared to outpatient parenteral antibiotic treatment for patients with **infective endocarditis**. This study is a randomized, controlled trial with a double-blind design to ensure unbiased results. The trial is expected to run from January 31, 2022, to December 31, 2026, with participant involvement lasting up to six months from diagnosis. The primary endpoint is a composite of unplanned hospitalization, all-cause mortality, unplanned cardiac surgery, and relapse of infective endocarditis within six months. Secondary endpoints include quality of life, patient satisfaction, cost analysis, and complications related to antibiotic administration.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, previous antibiotic treatment, and echocardiography results. Follow-up visits will be scheduled to monitor the patient's health status, adherence to the treatment regimen, and any adverse events. The end-of-study visit will assess the primary and secondary endpoints and gather final data on the participant's condition. The expected length of participant involvement is determined by the trial's duration, with early termination possible if significant adverse events occur or if the participant withdraws consent.

Inclusion criteria require participants to have left-sided native or prosthetic infective endocarditis, be 18 years or older, and have completed a minimum of ten days of appropriate parenteral antibiotic treatment. Exclusion criteria are not specified in the provided data. The trial aims to provide valuable insights into the efficacy and safety of oral versus parenteral antibiotic treatments, potentially influencing future therapeutic approaches for infective endocarditis.

The clinical trial involves the use of **AMOXICILLIN**, marketed under the name AMOXICILINA NORMON 1000 mg Comprimidos EFG, as the experimental medication. This pharmaceutical product is formulated as a **tablet** and is intended for **oral use**. The active substance, amoxicillin, is of chemical origin and is classified under the ATC code J01CA04. The maximum daily dose of amoxicillin administered in this trial is 4 grams, with a total maximum dose of 168 grams over a treatment period of up to 6 weeks. The medication is produced by Laboratorios Normon, S.A., and is not a pediatric formulation. The trial aims to evaluate the non-inferiority of outpatient oral antibiotic therapy compared to outpatient parenteral antibiotic treatment for infective endocarditis.

In addition to the experimental treatment, the study may involve the use of standard-of-care therapy, which could include a comparator treatment or placebo, depending on the specific design of the trial. The administration of the experimental medication and any non-experimental treatments will be closely monitored to ensure participant compliance with the dosing schedules. The trial's objective is to assess the efficacy and safety of oral antimicrobial treatment in comparison to outpatient parenteral therapy, with a focus on demonstrating non-inferiority in the management of infective endocarditis.

Efficacy in the clinical trial titled "Oral antimicrobial treatment vs. outpatient parenteral for infective endocarditis" will be assessed using a composite primary endpoint. This endpoint includes the occurrence of unplanned hospitalization due to any reason, all-cause mortality, unplanned cardiac surgery, and relapse of **infective endocarditis** (IE) within six months from diagnosis. Secondary endpoints will evaluate quality of life and patient satisfaction, costs of both interventions through a pharmacoeconomic analysis, and the number of complications related to parenteral and oral administration of antibiotics, such as catheter-related infections and Clostridium difficile diarrhea. Additionally, unplanned hospitalization, all-cause mortality, unplanned cardiac surgery, and relapse of IE rates will be assessed for each variable.