Clinical trial NCT04961528: ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.
Official title: ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE3
Conditions: Hemoptysis
Keywords: terlipressin
tranexamic acid
Lead sponsor: Assistance Publique - Hôpitaux de Paris
Sponsor class: OTHER
Collaborators: name: Ministry of Health, France
First posted: 2021-07-14
Enrollment: 315
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Number of patients with complete or partial resolution of hemoptysis without the use of any interventional procedure.
timeFrame: 3 days
Secondary outcomes:
measure: Rate of complete resolution of hemoptysis within 3 days, as previously defined
timeFrame: 3 days
measure: Rate of partial resolution of hemoptysis defined as recurrence < 50 ml
timeFrame: 3 days
measure: Rate of patients with total volume of hemoptysis < 200 ml
timeFrame: 3 days
measure: Rate of patients who need an endovascular treatment (bronchial arterial endovascular embolization)
timeFrame: 3 days
measure: Time between hospital admission and bronchial arterial endovascular embolization
timeFrame: 3 days
measure: Rate of patients who need a mechanical ventilation
timeFrame: 3 days
measure: Rate of specific adverse events
timeFrame: 3 days
measure: Rate of in-hospital mortality
timeFrame: 30 days
measure: Rate of patients with hemoptysis recurrence
timeFrame: 30 days
measure: Death rate
timeFrame: 30 days
Other outcomes:
Locations:
city: Paris
country: France
facility: AP-HP, Hôpital Européen Georges Pompidou
Study officials:
affiliation: AP-HP, Hôpital Européen Georges Pompidou, Paris
name: Benjamin Planquette, MD, PhD
role: STUDY_CHAIR
References: