Efficacy of Inhaled Tranexamic Acid and Terlipressin in the Immediate Management of Mild to Severe Hemoptysis: A Randomized Controlled Trial

The primary objective of this study is to evaluate the **efficacy** of inhaled tranexamic acid (TXA) and inhaled terlipressin (TER) compared to placebo (normal saline) in achieving immediate control of mild to severe **hemoptysis** within the first three days of hospitalization. This is clinically relevant as effective management of hemoptysis is critical to prevent further complications and improve patient outcomes. A hierarchical analysis will be conducted to compare TXA and TER, contingent upon demonstrating the superiority of both active treatments over placebo. If this initial comparison is unsuccessful, the comparison between TXA and TER will be considered exploratory.

The secondary objectives include: - Comparing active treatments (TXA and TER) to placebo in terms of complete and partial resolution of hemoptysis, 30-day hemoptysis recurrence rate, total volume of hemoptysis, and the need and timing of invasive procedures such as bronchial arterial endovascular embolization and mechanical ventilation. - Assessing safety, hospital mortality, and 30-day mortality. - Evaluating the comparison of TXA versus TER on the aforementioned parameters. - Identifying risk factors for hemoptysis recurrences.

The clinical trial involves participants diagnosed with **hemoptysis**, excluding cases related to cystic fibrosis. The study population comprises both male and female subjects aged between 18 and 90 years. Participants are required to have experienced mild to severe hemoptysis for less than 7 days, with a total expectorate blood volume ranging from 50 ml to 200 ml. Eligible individuals must have been admitted to an emergency department or ICU for less than 12 hours. The trial does not include a vulnerable population. Participants must be affiliated with social security and provide signed informed consent. For women of childbearing age, effective contraception is mandatory. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed to evaluate the efficacy of **tranexamic acid** and **terlipressin** in the treatment of mild to severe **hemoptysis**. This study is a randomized, double-blind, controlled trial with a hierarchical analysis approach. The trial aims to compare the effectiveness of inhaled tranexamic acid and terlipressin against a placebo, which is normal saline, in controlling hemoptysis within the first three days of hospitalization. The trial is expected to run from March 28, 2022, to January 28, 2026, with participant involvement lasting up to three days, depending on the treatment group assignment.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age (18-90 years), recent onset of hemoptysis (less than seven days), and admission to an emergency department or ICU within the last 12 hours. Following the screening, eligible participants will be randomized to receive either tranexamic acid, terlipressin, or placebo. The primary endpoint is the proportion of patients achieving complete or partial resolution of hemoptysis without any interventional procedures within three days. Secondary endpoints include the rate of complete and partial resolution, total hemoptysis volume, need for endovascular treatment, and various safety outcomes.

Study visits will include follow-up assessments to monitor the resolution of hemoptysis and any adverse events. The end-of-study visit will occur at the conclusion of the three-day treatment period or earlier if the participant experiences significant adverse events or requires interventional procedures. Conditions that may lead to early termination from the study include the need for bronchial arterial endovascular embolization or the occurrence of severe adverse events such as acute myocardial ischemia or symptomatic venous thromboembolism. The trial's design ensures rigorous assessment of the investigational treatments' efficacy and safety in managing hemoptysis.

The clinical trial involves the administration of **TRANEXAMIC ACID**, which is provided in a **solution for injection** form. The active substance, tranexamic acid, is of chemical origin. The maximum daily dose is 1500 mg, with a total maximum dose of 4500 mg over a treatment period of up to 3 days. The route of administration is **inhalation use**, facilitated by a nebulizer device, specifically the INT'AIR MEDICAL RN300. This device is equipped with a CE mark, ensuring compliance with European safety standards. The inhalation therapy is designed to deliver the medication directly to the respiratory system, optimizing its efficacy in controlling hemoptysis.

**TERLIPRESSIN** is another experimental medication used in this trial, also provided as a **solution for injection**. The active substance, terlipressin, is administered via inhalation, similar to tranexamic acid, using the same nebulizer device. The maximum daily dose for terlipressin is 3 mg, with a total maximum dose of 9 mg over a 3-day treatment period. The inhalation route is chosen to target the respiratory system directly, aiming to manage hemoptysis effectively.

The trial also includes a **placebo** treatment, consisting of **NaCl 0.9%**. This placebo is administered via inhalation, serving as a control to evaluate the efficacy of the experimental treatments. The use of normal saline as a placebo allows for a direct comparison of the therapeutic effects of tranexamic acid and terlipressin against a non-active treatment. The administration schedule and compliance monitoring are consistent across all treatment arms to ensure the reliability of the trial outcomes.

The efficacy of the clinical trial titled "AcTIVE - ACid tranexamic or Terlipressin for Initial emergency treatment of mild to seVere hEmoptysis: a randomized Trial" will be assessed by evaluating the immediate control of mild to severe **hemoptysis** within the first 3 days of hospitalization. The primary endpoint is the proportion of patients achieving complete or partial resolution of hemoptysis without the need for any interventional procedure. Complete resolution is defined as the absence of recurrence within 3 days, while partial resolution is defined as a recurrence of hemoptysis of less than 50 mL within the same period.

Secondary endpoints include the rate of complete and partial resolution of hemoptysis within 3 days, the proportion of patients with a total hemoptysis volume of less than 200 mL within 3 days, and the rate of patients requiring endovascular treatment such as bronchial arterial endovascular embolization within 3 days. Additional secondary endpoints are the time from hospital admission to endovascular treatment, in-hospital mortality, 30-day recurrence rate of hemoptysis, 30-day mortality, and the rate of specific adverse events including acute myocardial ischemia, symptomatic venous thromboembolism, hyponatremia, and bronchospasm. The trial will also consider variables such as age, sex, baseline expectorated blood volume, cause of hemoptysis, previous hemoptysis, coagulation disorders, need for mechanical ventilation, and treatment group in assessing the risk of hemoptysis recurrence.