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

Assistance Publique - Hôpitaux de Paris

Status and phase: Enrolling; Phase 3

Conditions: Hemoptysis

Treatments: Drug: Tranexamic Acid 500 MG; Drug: Terlipressin; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT04961528

2020-005931-58 (EudraCT Number)

APHP200043

PHRC-19-0412 (Other Grant/Funding Number)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 315 estimated patients

Sex: All

Ages: 18 to 90 years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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315 participants in 3 patient groups, including a placebo group

Terlipressin

Experimental group

Description:

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

Treatment:

Drug: Terlipressin

Tranexamic Acid

Experimental group

Description:

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.

Treatment:

Drug: Tranexamic Acid 500 MG

Normal Saline Placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: Placebo