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Trial record 5 of 26 for:    terlipressin | Phase 3

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

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ClinicalTrials.gov Identifier: NCT04961528
Recruitment Status : Not yet recruiting
First Posted : July 14, 2021
Last Update Posted : July 20, 2021
Sponsor:
Collaborator:
Ministry of Health, France
Information provided by (Responsible Party):
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.


Condition or disease Intervention/treatment Phase
Hemoptysis Drug: Tranexamic Acid 500 MG Drug: Terlipressin Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 315 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: ACid Tranexamic or Terlipressin for Initial Emergency Treatment of Mild to seVere hEmoptysis: a Randomized Trial.
Estimated Study Start Date : September 1, 2021
Estimated Primary Completion Date : September 15, 2023
Estimated Study Completion Date : October 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Terlipressin

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

Drug: Terlipressin

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


Experimental: Tranexamic Acid

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.

Drug: Tranexamic Acid 500 MG

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


Placebo Comparator: Normal Saline Placebo

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.

Drug: Placebo

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.

Other Name: Normal saline placebo




Primary Outcome Measures :
  1. Number of patients with complete or partial resolution of hemoptysis without the use of any interventional procedure. [ Time Frame: 5 days ]

    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 :
  1. Rate of complete resolution of hemoptysis within 5 days, as previously defined [ Time Frame: 5 days ]
    Complete resolution of hemoptysis, as previously defined

  2. Rate of partial resolution of hemoptysis defined as recurrence < 50 ml [ Time Frame: 5 days ]
    Partial resolution of hemoptysis, as previously defined

  3. Rate of patients with total volume of hemoptysis < 200 ml [ Time Frame: 5 days ]
    Total volume of hemoptysis < 200 ml

  4. Rate of patients who need an endovascular treatment (bronchial arterial endovascular embolization) [ Time Frame: 5 days ]
    Need of invasive procedure such as bronchial arterial endovascular embolization

  5. Time between hospital admission and bronchial arterial endovascular embolization [ Time Frame: 5 days ]
    Time between hospital admission and endovascular treatment

  6. Rate of patients who need a mechanical ventilation [ Time Frame: 5 days ]
    Need of invasive procedure such as mechanical ventilation,

  7. Rate of specific adverse events [ Time Frame: 5 days ]
    Specific Adverse Events (AE) : acute myocardial ischemia, symptomatic venous thromboembolism, hyponatremia (<130 mmol/L), bronchospasm (defined by the need of short-acting bronchodilatator).

  8. Rate of in-hospital mortality [ Time Frame: 30 days ]
  9. Rate of patients with hemoptysis recurrence [ Time Frame: 30 days ]
  10. Death rate [ Time Frame: 30 days ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04961528


Contacts
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Contact: Karine Goude-Ory 01 44 84 17 22 karine.goude@aphp.fr
Contact: Cléo Bourgeois 01 56 09 56 38 cleo.bourgeois@aphp.fr

Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Ministry of Health, France
Investigators
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Study Chair: Benjamin Planquette, MD, PhD AP-HP, Hôpital Européen Georges Pompidou, Paris
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Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT04961528    
Other Study ID Numbers: APHP200043
2020-005931-58 ( EudraCT Number )
PHRC-19-0412 ( Other Grant/Funding Number: French ministry of health )
First Posted: July 14, 2021    Key Record Dates
Last Update Posted: July 20, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
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
Supporting Materials: Study Protocol
Informed Consent Form (ICF)
Time Frame: Two years after the last publication
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).


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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Assistance Publique - Hôpitaux de Paris:
terlipressin
tranexamic acid
Additional relevant MeSH terms:
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Terlipressin
Hemoptysis
Emergencies
Disease Attributes
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Hemorrhage
Signs and Symptoms, Respiratory
Tranexamic Acid
Antifibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Hemostatics
Coagulants
Antihypertensive Agents
Vasoconstrictor Agents