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

Primary Purpose

Hemoptysis

Status
Recruiting
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Tranexamic Acid 500 MG
Terlipressin
Placebo
Sponsored by
Assistance Publique - Hôpitaux de Paris
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hemoptysis focused on measuring terlipressin, tranexamic acid

Eligibility Criteria

18 Years - 90 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients over 18 years, under 90 years
  • Mild to severe hemoptysis that has been going on for less than 72 hours
  • 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)
  • Absolute need for anticoagulant treatment at curative dosage (recent venous thrombo-embolism in the 6 past months)
  • 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

Sites / Locations

  • AP-HP, Hôpital Européen Georges PompidouRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

Terlipressin

Tranexamic Acid

Normal Saline Placebo

Arm Description

Dosage: 1 mg /5 ml Pharmaceutical form: solution for infusion Posology: 1 mg /8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers

Dosage : 500 mg /5 ml Pharmaceutical form: solution for infusion Posology (and adjustments based on toxicity) : 500 mg/ 8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.

Dose : normal saline solution (NaCl 0.9%) Pharmaceutical form : solution for infusion Posology : 5ml / 8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.

Outcomes

Primary Outcome Measures

Number of patients with complete or partial resolution of hemoptysis without the use of any interventional procedure.
Efficacy of inhaled tranexamic acid and inhaled terlipressin versus placebo (normal saline) in immediate control of mild to severe hemoptysis within the first 5 days of hospitalization. A complete resolution of hemoptysis is defined by absence of recurrence within 5 days; partial resolution is defined as hemoptysis recurrence < 50 ml within the first 5 days

Secondary Outcome Measures

Rate of complete resolution of hemoptysis within 5 days, as previously defined
Complete resolution of hemoptysis, as previously defined
Rate of partial resolution of hemoptysis defined as recurrence < 50 ml
Partial resolution of hemoptysis, as previously defined
Rate of patients with total volume of hemoptysis < 200 ml
Total volume of hemoptysis < 200 ml
Rate of patients who need an endovascular treatment (bronchial arterial endovascular embolization)
Need of invasive procedure such as bronchial arterial endovascular embolization
Time between hospital admission and bronchial arterial endovascular embolization
Time between hospital admission and endovascular treatment
Rate of patients who need a mechanical ventilation
Need of invasive procedure such as mechanical ventilation,
Rate of specific adverse events
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 in-hospital mortality
Rate of patients with hemoptysis recurrence
Death rate

Full Information

First Posted
July 5, 2021
Last Updated
May 12, 2022
Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France
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1. Study Identification

Unique Protocol Identification Number
NCT04961528
Brief Title
ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.
Acronym
ACTIVE
Official Title
ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
May 2022
Overall Recruitment Status
Recruiting
Study Start Date
March 27, 2022 (Actual)
Primary Completion Date
March 30, 2024 (Anticipated)
Study Completion Date
April 30, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Assistance Publique - Hôpitaux de Paris
Collaborators
Ministry of Health, France

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hemoptysis
Keywords
terlipressin, tranexamic acid

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
315 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Terlipressin
Arm Type
Experimental
Arm Description
Dosage: 1 mg /5 ml Pharmaceutical form: solution for infusion Posology: 1 mg /8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers
Arm Title
Tranexamic Acid
Arm Type
Experimental
Arm Description
Dosage : 500 mg /5 ml Pharmaceutical form: solution for infusion Posology (and adjustments based on toxicity) : 500 mg/ 8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.
Arm Title
Normal Saline Placebo
Arm Type
Placebo Comparator
Arm Description
Dose : normal saline solution (NaCl 0.9%) Pharmaceutical form : solution for infusion Posology : 5ml / 8 hours Treatment duration: 5 days Method and route of administration: inhalation using the same jet nebulizers (INT'AIR Medical RN 300) in all Investigating centers.
Intervention Type
Drug
Intervention Name(s)
Tranexamic Acid 500 MG
Intervention Description
Jet nebulization (a device connected by tubing to compressed air or oxygen to flow at high velocity through a liquid medicine to turn it into an aerosol, which is then inhaled by the patient). The nebulization lasts 10 minutes. Posology: 500 mg x 3/day (= 500 mg / 8 hours) Treatments duration: 5 days
Intervention Type
Drug
Intervention Name(s)
Terlipressin
Intervention Description
Jet nebulization (a device connected by tubing to compressed air or oxygen to flow at high velocity through a liquid medicine to turn it into an aerosol, which is then inhaled by the patient). The nebulization lasts 10 minutes. Posology: 1 mg x 3/day (= 1 mg / 8 hours) Treatments duration: 5 days
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Normal saline placebo
Intervention Description
Jet nebulization (a device connected by tubing to compressed air or oxygen to flow at high velocity through a liquid medicine to turn it into an aerosol, which is then inhaled by the patient). The nebulization lasts 10 minutes. Posology: 5ml x 3/day (= 5 ml / 8 hours) Treatments duration: 5 days.
Primary Outcome Measure Information:
Title
Number of patients with complete or partial resolution of hemoptysis without the use of any interventional procedure.
Description
Efficacy of inhaled tranexamic acid and inhaled terlipressin versus placebo (normal saline) in immediate control of mild to severe hemoptysis within the first 5 days of hospitalization. A complete resolution of hemoptysis is defined by absence of recurrence within 5 days; partial resolution is defined as hemoptysis recurrence < 50 ml within the first 5 days
Time Frame
5 days
Secondary Outcome Measure Information:
Title
Rate of complete resolution of hemoptysis within 5 days, as previously defined
Description
Complete resolution of hemoptysis, as previously defined
Time Frame
5 days
Title
Rate of partial resolution of hemoptysis defined as recurrence < 50 ml
Description
Partial resolution of hemoptysis, as previously defined
Time Frame
5 days
Title
Rate of patients with total volume of hemoptysis < 200 ml
Description
Total volume of hemoptysis < 200 ml
Time Frame
5 days
Title
Rate of patients who need an endovascular treatment (bronchial arterial endovascular embolization)
Description
Need of invasive procedure such as bronchial arterial endovascular embolization
Time Frame
5 days
Title
Time between hospital admission and bronchial arterial endovascular embolization
Description
Time between hospital admission and endovascular treatment
Time Frame
5 days
Title
Rate of patients who need a mechanical ventilation
Description
Need of invasive procedure such as mechanical ventilation,
Time Frame
5 days
Title
Rate of specific adverse events
Description
Specific Adverse Events (AE) : acute myocardial ischemia, symptomatic venous thromboembolism, hyponatremia (<130 mmol/L), bronchospasm (defined by the need of short-acting bronchodilatator).
Time Frame
5 days
Title
Rate of in-hospital mortality
Time Frame
30 days
Title
Rate of patients with hemoptysis recurrence
Time Frame
30 days
Title
Death rate
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients over 18 years, under 90 years Mild to severe hemoptysis that has been going on for less than 72 hours 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) Absolute need for anticoagulant treatment at curative dosage (recent venous thrombo-embolism in the 6 past months) 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Karine Goude-Ory
Phone
01 44 84 17 22
Email
karine.goude@aphp.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Cléo Bourgeois
Phone
01 56 09 56 38
Email
cleo.bourgeois@aphp.fr
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Benjamin Planquette, MD, PhD
Organizational Affiliation
AP-HP, Hôpital Européen Georges Pompidou, Paris
Official's Role
Study Chair
Facility Information:
Facility Name
AP-HP, Hôpital Européen Georges Pompidou
City
Paris
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Benjamin Planquette, MD
Email
benjamin.planquette@aphp.fr

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Individual participant data (IPD) that underlie results in publication could be shared. IPD detailed in the protocol of a planned metaanalysis could be shared
IPD Sharing Time Frame
Two years after the last publication
IPD Sharing Access Criteria
Data sharing must be accepted by the sponsor and the PI based on a scientific project and scientific involvement of the PI team. Collaboration will be fostered. Teams wishing obtain IPD must meet the sponsor and PI team to present scientific (and commercial) purpose, IPD needed, format of data transmission, and timeframe. Technical feasability and financial support will be discussed before mandatory contractual agreement. Processing of shared data must comply with European General Data Protection Regulation (GDPR).

Learn more about this trial

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

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