Cluster randomised trial of low molecular weight heparins - Directly through Epic

The primary objective of this study is to evaluate whether treatment with any of the low molecular weight **heparins** (LMWHs) increases the risk of bleeding requiring intervention during admission or death within 30 days in patients with an indication for LMWHs, compared with one of the other LMWHs. This is clinically relevant as it addresses the safety profile of LMWHs, which are commonly used in the management of **venous thromboembolism**, and aims to optimize patient outcomes by identifying potential risks associated with their use.

Secondary objectives include investigating the comparable risk in patients treated with enoxaparin, dalteparin, or tinzaparin regarding:

• All-cause 30-day mortality
• All-cause 365-day mortality
• Blood transfusion during admission
• Pulmonary embolism at 30 days
• Heparin-induced thrombocytopenia
• Liver failure
• Length of hospital admission
• Days alive out of hospital

The clinical trial focuses on patients with **venous thromboembolism** who are admitted to the hospital and have an indication for treatment with low molecular weight heparins. The study population includes both male and female subjects, encompassing an age range that includes adults and the elderly. The trial involves a vulnerable population, as indicated by the inclusion of hospitalized patients. The sponsor has not provided information regarding the total number of participants. Participants are selected based on their admission to the hospital and the requirement for low molecular weight heparin treatment, with inclusion limited to their first admission during the study period. Lifestyle considerations such as diet, physical activity, or habits are not specified in the available data.

The clinical trial is designed as a **cluster randomized** study to evaluate the safety and efficacy of low molecular weight heparins, specifically **tinzaparin** and **dalteparin sodium**, in patients with **venous thromboembolism**. The trial aims to assess whether treatment with these anticoagulants increases the risk of major bleeding requiring blood transfusion or results in all-cause mortality within 30 days. The study is conducted in a **double-blind** manner to ensure unbiased results, with participants randomly assigned to receive either tinzaparin or dalteparin sodium via **subcutaneous injection**. The trial is categorized as a phase IV study, focusing on already approved medicinal products, and is considered low intervention due to its minimal additional risk compared to standard clinical practice.

The trial is expected to run from March 31, 2023, to March 31, 2025, with a maximum treatment period of 52 weeks for each participant. The study includes several key visits: an initial screening visit to confirm eligibility based on the principal inclusion criteria, which require patients to be admitted to the hospital with an indication for low molecular weight heparin treatment. Follow-up visits will be scheduled to monitor the primary endpoint of major bleeding and all-cause mortality at 30 days, as well as secondary endpoints such as 365-day mortality, blood transfusion during admission, pulmonary embolism at 30 days, heparin-induced thrombocytopenia, liver failure, length of hospital admission, and days alive out of the hospital. The end-of-study visit will conclude the participant's involvement, ensuring all data is collected and any adverse events are addressed.

Participants are expected to be involved in the study for the duration of their hospital admission and up to 30 days post-discharge, with the possibility of early termination if they experience significant adverse events or if they withdraw consent. The trial's design ensures that all procedures adhere to ethical standards and regulatory requirements, maintaining the safety and well-being of all participants throughout the study duration.

The clinical trial involves the administration of **TINZAPARIN**, a low molecular weight heparin, as an experimental medication. Tinzaparin is provided in a pharmaceutical form identified as PHF00231MIG. The medication is administered via **subcutaneous injection**. The dosage is calculated based on the participant's weight, with a maximum daily dose of 175 IU/kg. The treatment period for Tinzaparin is set to a maximum of 52 weeks. Compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the protocol.

Another experimental medication used in the trial is **DALTEPARIN SODIUM**, also a low molecular weight heparin. Dalteparin is similarly provided in the pharmaceutical form PHF00231MIG and is administered through **subcutaneous use**. The dosage for Dalteparin is also weight-based, with a maximum daily dose of 200 IU/kg. The treatment duration for Dalteparin is up to 52 weeks. Participant compliance with the dosing regimen is closely monitored to maintain the integrity of the trial data.

Both Tinzaparin and Dalteparin are classified as anticoagulants and are not pediatric formulations. They are used in the trial to evaluate the risk of bleeding or death within 30 days in patients with an indication for low molecular weight heparins. The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The administration and dosing schedules are strictly adhered to, with participant compliance being a critical component of the study's success.

The efficacy of the clinical trial will be assessed by evaluating the primary and secondary endpoints. The primary endpoint is the occurrence of major bleeding requiring blood transfusion and **all-cause mortality** at 30 days. Secondary endpoints include all-cause 30-day mortality, all-cause 365-day mortality, blood transfusion during admission, pulmonary embolism at 30 days, heparin-induced thrombocytopenia, liver failure, length of hospital admission, and days alive out of the hospital.

Data collection will occur at specified time points, including during hospital admission and at 30 and 365 days post-treatment initiation. The trial will utilize validated clinical assessments and laboratory tests to measure these endpoints. The study is designed to compare the effects of different low molecular weight heparins, specifically **tinzaparin** and **dalteparin sodium**, administered via subcutaneous injection. The trial aims to determine if these treatments increase the risk of bleeding or mortality in patients with an indication for low molecular weight heparins.