ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.

Phase 3

Recruiting

• Conditions: Hemoptysis
• Interventions: Drug: Placebo; Drug: Tranexamic Acid 500 MG; Drug: Terlipressin

• Registration Number: NCT04961528
• Lead Sponsor: Assistance Publique - Hôpitaux de Paris

Brief Summary

The study aims is to verify the hypothetize that inhaled Tranexamic Acid (TXA) or Terlipressin (TER) will be associated with an increase in the rapid control of hemoptysis without side-effects.

This randomized double-blind multicenter triple arm trial compares the administration of TXA to TER to placebo in patients with mild to severe hemoptysis.

Detailed Description

In over 90% of cases, hemoptysis is due to a bronchial or non-bronchial systemic arterial mechanism.

Embolization of Bronchial Arteries (EBA) is the main specific treatment but is not easily available. Medical treatment for hemoptysis is not evidence-based.

For this study, the investigators will dispense trial drugs using inhalation route which has not been evaluated in mild to severe hemoptysis in previous trials. In addition, as opposed to previous trials, the investigators will assess the safety of trials drugs during hospital stay.

Acid tranexamic (TXA), an antifibrinolytic drug, reduces bleeding in uterine and traumatic haemorrhage by blocking the action of plasmin on fibrin. Intravenous terlipressin (TER), a vasoconstrictor, contributes to control digestive haemorrhage but presents many contraindication when administrated by intravenous route.

The investigator hypothetize that inhaled antifibrinolytic (TXA) or vasoconstrictor (TER) will be associated with an increase in the rapid control of hemoptysis without side-effects.

Patients will be randomized into 3 groups:

* Active treatment 1: Tranexamic Acid 500 mg three times a day (every 8 hours) for 5 days.

* Active treatment 2: Terlipressin 1 mg three times a day (every 8 hours) for 5 days.

* Placebo: normal saline nebulization three times a day (every 8 hours) for 5 days.

Using a hierarchical analysis, the comparison between TXA and TER will be tested once superiority on efficacy of both inhaled TXA and TER vs placebo is demonstrated. The above secondary objectives will then be assessed for the comparison of TXA versus TER.

Study Timeline

• Study First Submitted: 2021-07-05
• Study First Submitted QC: 2021-07-05
• Study First Posted: 2021-07-14
• Study Start: 2022-03-27
• Status Verified: 2024-05
• Last Update Submitted: 2024-05-02
• Last Update Posted: 2024-05-03
• Primary Completion: 2025-12-31
• Study Completion: 2026-01-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 315

Inclusion Criteria

• Patients over 18 years, under 90 years
• Mild to severe hemoptysis that has been going on for less than 7 days
• Total expectorate blood ranging from 50 ml to 200 ml
• Admission in emergency department or ICU for less than 12 hours
• Social security affiliation
• Signed informed consent
• For child-bearing aged women, efficient contraception includes oral oestrogen- progestin, oral progestin, progestin implants and all types of intrauterine devices

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Exclusion Criteria

• Need for mechanical ventilation

• Cystic fibrosis

• Pregnancy or breast feeding

• Contraindication for contrast agents injection (renal failure with creatinin clearance < 30mL/min, know allergy to contrast agents injection)

• Known hypersensitivity to TXA or TER or one of its excipients

• Know previous cardiac arrhythmia (atrial fibrillation, atrial flutter..)

• Contraindication to TXA (including renal failure with creatinin clearance < 30mL/min) or TER therapy :

  • acute myocardial infarction in the 6 past months,
  • intrathecal injection in the 3 past months,
  • seizure in the past 3 months

• Participation in another interventional study or being in the exclusion period at the end of a previous study.

• Patient under tutorship or / guardianship, and incapable to give informed consent

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Normal Saline Placebo	Placebo	Dose : normal saline solution (NaCl 0.9%) Pharmaceutical form : solution for infusion Posology : 5ml / 8 hours Treatment duration: 3 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.
Tranexamic Acid	Tranexamic Acid 500 MG	Dosage : 500 mg /5 ml Pharmaceutical form: solution for infusion Posology (and adjustments based on toxicity) : 500 mg/ 8 hours Treatment duration: 3 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.
Terlipressin	Terlipressin	Dosage: 1 mg /5 ml Pharmaceutical form: solution for infusion Posology: 1 mg /8 hours Treatment duration: 3 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers

Primary Outcome Measures

Name	Time	Method
Number of patients with complete or partial resolution of hemoptysis without the use of any interventional procedure.	3 days	Efficacy of inhaled tranexamic acid and inhaled terlipressin versus placebo (normal saline) in immediate control of mild to severe hemoptysis within the first 3 days of hospitalization.; A complete resolution of hemoptysis is defined by absence of recurrence within 3 days; partial resolution is defined as hemoptysis recurrence \< 50 ml within the first 3 days

Secondary Outcome Measures

Name	Time	Method
Rate of patients with hemoptysis recurrence	30 days
Death rate	30 days
Rate of patients who need a mechanical ventilation	3 days	Need of invasive procedure such as mechanical ventilation,
Rate of in-hospital mortality	30 days
Time between hospital admission and bronchial arterial endovascular embolization	3 days	Time between hospital admission and endovascular treatment
Rate of patients with total volume of hemoptysis < 200 ml	3 days	Total volume of hemoptysis \< 200 ml
Rate of specific adverse events	3 days	Specific Adverse Events (AE) : acute myocardial ischemia, symptomatic venous thromboembolism, hyponatremia (\<130 mmol/L), bronchospasm (defined by the need of short-acting bronchodilatator).
Rate of patients who need an endovascular treatment (bronchial arterial endovascular embolization)	3 days	Need of invasive procedure such as bronchial arterial endovascular embolization
Rate of partial resolution of hemoptysis defined as recurrence < 50 ml	3 days	Partial resolution of hemoptysis, as previously defined
Rate of complete resolution of hemoptysis within 3 days, as previously defined	3 days	Complete resolution of hemoptysis, as previously defined

Trial Locations

Locations (1)

AP-HP, Hôpital Européen Georges Pompidou; 🇫🇷 Paris, France