PLATFORM-COVID study; Platform randomised trial of treatments for COVID-19 in general practice

The primary objective of the PLATFORM-COVID study is to evaluate the **effectiveness** of treatments administered in primary care settings on the time to recovery for patients with **COVID-19** in the community who are at an elevated risk of experiencing a complicated illness course. This objective is clinically relevant as it aims to optimize treatment strategies for high-risk patients, potentially reducing the duration and severity of illness, and improving patient outcomes. Additionally, the study seeks to establish a platform trial infrastructure within Dutch primary care, facilitating future nationwide trials for COVID-19 and other emerging diseases. This infrastructure is intended to enhance the capacity for rapid and efficient evaluation of multiple interventions, compared against standard care, in response to public health needs.

The clinical trial involves **patients with COVID-19** in the community, specifically those referred by their general practitioner and at higher risk of a complicated illness course. The study population includes both male and female participants aged 18 years and older, with a focus on individuals aged 65 and above or those aged 18-64 with specific comorbidities. These comorbidities include chronic respiratory and cardiac disorders, diabetes mellitus, severe kidney dysfunction, reduced immunity, untreated HIV infection, severe liver disease, and morbid obesity. Participants are required to have a positive test for SARS-CoV-2 infection and exhibit symptoms of COVID-19 for fewer than 15 days. The trial does not target a vulnerable population specifically. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize the inclusion of individuals who are willing and able to give informed consent and comply with all trial procedures.

The clinical trial is designed to evaluate the effectiveness of treatments for **COVID-19** in primary care settings, specifically targeting patients at higher risk of a complicated illness course. The trial employs a **randomized**, **controlled**, and platform design, allowing for multiple interventions to be compared against standard care. The trial is set to run from October 1, 2022, to October 1, 2023, with the primary endpoint being the time to recovery within 28 days from randomization, as measured by a daily diary where participants report their recovery status.

Participants will be involved in the study for a maximum of 28 days, with the treatment period not exceeding 14 days. The study includes an initial screening visit to confirm eligibility, followed by regular follow-up visits to monitor progress and collect data on primary and secondary endpoints, such as hospital admissions and the duration of severe symptoms. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

Inclusion criteria require participants to be aged 18 years or older, with a positive test for **SARS-CoV-2** infection and symptoms of **COVID-19**. Participants must also have certain comorbidities or be aged 65 or older. Exclusion criteria are not specified in the provided data. Conditions for early termination from the study include withdrawal of consent or any adverse events that compromise participant safety. The trial aims to establish a standing infrastructure for future nationwide trials in primary care for **COVID-19** and other emerging diseases.

The clinical trial involves the administration of **Montelukast Sandoz 10 mg**, a **film-coated tablet** containing the active substance **montelukast**. This medication is chemically synthesized and is provided by Sandoz B.V. The pharmaceutical form is a film-coated tablet, designed for oral administration. Participants in the trial will receive a daily dose of 10 mg, with a maximum total dose of 140 mg over a treatment period of 14 days. The administration route is oral, ensuring ease of use and compliance. The trial aims to evaluate the effectiveness of this treatment in patients with COVID-19 who are at higher risk of a complicated illness course.

In addition to the experimental treatment, the study includes a comparison with standard-of-care therapy, referred to as "care as usual." This non-experimental treatment serves as a control to assess the relative effectiveness of Montelukast Sandoz. The trial is structured as a platform study, allowing for the inclusion of multiple interventions, which will be compared against the standard care provided in primary care settings. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol.

Efficacy in the clinical trial will be assessed primarily by measuring the **time to recovery** from suspected COVID-19 infection within 28 days from randomization. This primary endpoint is defined as the first instance that a participant reports feeling recovered. Participants will record their recovery status daily in a diary by answering the question, "Do you feel fully recovered today? (i.e., symptoms associated with illness are no longer a problem)" with either 'yes' or 'no'.

Secondary endpoints will include various health outcomes such as hospital admission, hospital assessment without admission, oxygen administration, intensive care unit admission, duration of severe symptoms, sustained recovery, contacts with health services, consumption of antibiotics, WHO Well-being Index, daily rating of how well participants feel, safety, and death. These parameters will provide a comprehensive assessment of the treatment's impact on the participants' health and well-being.