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Trial record 1 of 1 for:    NCT04640194
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A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19 (TRISTARDS)

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ClinicalTrials.gov Identifier: NCT04640194
Recruitment Status : Recruiting
First Posted : November 23, 2020
Last Update Posted : July 13, 2021
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Brief Summary:

This is a study in adults with severe breathing problems because of COVID-19. People who are in hospital on breathing support can participate in the study. The purpose of the study is to find out whether a medicine called alteplase helps people get better faster.

The study has 2 parts. In the first part, participants are put into 3 groups by chance. Participants in 2 of the groups get 2 different doses of alteplase, in addition to standard treatment.

Participants in the third group get standard treatment. In the second part of the study, participants are put into 2 groups by chance. One group gets alteplase and standard treatment. The other group gets only standard treatment. Alteplase is given as an infusion into a vein. In both study parts, treatments are given for 5 days. Doctors monitor patients and check whether their breathing problems improve. They compare results between the groups after 1 month.

Participants are in the study for 3 months.


Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: Alteplase Procedure: Standard of care Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 270 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: The study comprises two parts: Part 1 (dose-finding, Phase IIb) and Part 2 (confirmatory, Phase III)
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: The TRISTARDS Trial - ThRombolysIS Therapy for ARDS A Phase IIb/III Operationally Seamless, Open-label, Randomised, Sequential, Parallel-group Adaptive Study to Evaluate the Efficacy and Safety of Daily Intravenous Alteplase Treatment Given up to 5 Days on Top of Standard of Care (SOC) Compared With SOC Alone, in Patients With Acute Respiratory Distress Syndrome (ARDS) Triggered by COVID-19
Actual Study Start Date : December 16, 2020
Estimated Primary Completion Date : June 7, 2022
Estimated Study Completion Date : September 1, 2022


Arm Intervention/treatment
Control group
Standard of care alone
Procedure: Standard of care
Standard of Care (SOC) includes any supportive measures applied in hospital, specifically on an intensive care unit (ICU), such as for example the use of non-invasive or invasive ventilation, oxygen masks, haemodynamic support, if needed, sedation, as well as medical therapies commonly used in patients suffering from acute respiratory distress syndrome (ARDS) or its complications. SOC should include best possible treatment regimen established locally and should be in line with current guidelines for ARDS treatment.

Experimental: Treatment group A
Alteplase (low dose) on top of standard of care
Drug: Alteplase
Alteplase

Procedure: Standard of care
Standard of Care (SOC) includes any supportive measures applied in hospital, specifically on an intensive care unit (ICU), such as for example the use of non-invasive or invasive ventilation, oxygen masks, haemodynamic support, if needed, sedation, as well as medical therapies commonly used in patients suffering from acute respiratory distress syndrome (ARDS) or its complications. SOC should include best possible treatment regimen established locally and should be in line with current guidelines for ARDS treatment.

Experimental: Treatment group B
Alteplase (high dose) on top of standard of care
Drug: Alteplase
Alteplase

Procedure: Standard of care
Standard of Care (SOC) includes any supportive measures applied in hospital, specifically on an intensive care unit (ICU), such as for example the use of non-invasive or invasive ventilation, oxygen masks, haemodynamic support, if needed, sedation, as well as medical therapies commonly used in patients suffering from acute respiratory distress syndrome (ARDS) or its complications. SOC should include best possible treatment regimen established locally and should be in line with current guidelines for ARDS treatment.




Primary Outcome Measures :
  1. Time to clinical improvement or hospital discharge [ Time Frame: Up to day 28 ]

    Time from randomisation to either an improvement of two points on the 11-point WHO Clinical Progression Scale or discharge from the hospital, whichever comes first.

    The WHO Clinical Progression Scale ranges from 0 to 10. A higher score indicates a worsening of the patient status.



Secondary Outcome Measures :
  1. All cause mortality [ Time Frame: At day 28 ]
  2. Number of ventilator-free days [ Time Frame: From start of treatment to day 28 ]
  3. Improvement of Sequential (sepsis-related) Organ Failure Assessment (SOFA) score by ≥2 points [ Time Frame: From baseline to end of day 6 ]
    The SOFA score ranges from 0 to 6. A higher score indicates a worsening of the symptoms.

  4. Number of major bleeding events (MBE) [ Time Frame: Up to day 6 ]
    according to International Society on Thrombosis and Haemostasis (ISTH) definition

  5. Daily average PaO2/FiO2 ratio (or inferred PaO2/FiO2 ratio from SpO2) change [ Time Frame: From baseline to end of day 6 ]
    PaO2: partial oxygen pressure in arterial blood FiO2: fraction of inspired oxygen SpO2: Oxygen saturation

  6. All-cause mortality or on mechanical ventilation [ Time Frame: At day 28 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥ 18 years (or above legal age, e.g. UK ≥16 years)
  • ARDS with PaO2*/FiO2 ratio >100 and ≤300, either on non-invasive ventilator support, OR on mechanical ventilation (<48 hours since intubation),

    • with bilateral opacities in chest X-ray or CT scan (not fully explained by effusions, lobar/lung collapse, or nodules)
    • with respiratory failure (not fully explained by cardiac failure/fluid overload) (*or estimation of PaO2/FiO2 from pulse oximetry (SpO2/FiO2))
  • SARS-CoV-2 positive (laboratory-confirmed reverse transcription polymerase chain reaction (RT PCR) test)
  • Fibrinogen level ≥ upper limit of normal (according to local laboratory)
  • D-Dimer ≥ 3-fold of upper limit of normal (ULN) according to local laboratory
  • Signed and dated written informed consent in accordance with ICH Good Clinical Practice (GCP) and local legislation prior to admission to the Trial

Exclusion Criteria:

  • Massive confirmed pulmonary embolism (PE) with haemodynamic instability at trial entry
  • Patients on mechanical ventilation for longer than 48 hours
  • Chronic pulmonary disease i.e. with known forced expiratory volume in 1 second (FEV1) <50%, requiring home oxygen, or oral steroid therapy or hospitalisation for exacerbation within 12 months, or significant chronic pulmonary disease in the Investigator's opinion, or primary pulmonary arterial hypertension
  • Has a Do-Not-Intubate (DNI) or Do-Not-Resuscitate (DNR) order
  • In the opinion of the investigator not expected to survive for > 48 hours after admission
  • Patients with known hypersensitivity to the active substance alteplase, gentamicin (a trace residue from the manufacturing process) or to any of the excipients
  • Significant bleeding disorder at present or within the past 3 months, known haemorrhagic diathesis
  • Patients receiving effective oral anticoagulant treatment, e.g. vitamin K antagonists with International normalised ratio (INR) >1.3, or any direct oral anticoagulant within the past 48 hours Further exclusion criteria apply.

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): NCT04640194


Contacts
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Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com

Locations
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Sponsors and Collaborators
Boehringer Ingelheim
Additional Information:
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Responsible Party: Boehringer Ingelheim
ClinicalTrials.gov Identifier: NCT04640194    
Other Study ID Numbers: 0135-0347
2020-002913-16 ( EudraCT Number )
First Posted: November 23, 2020    Key Record Dates
Last Update Posted: July 13, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description:

After the study is completed and the primary manuscript is accepted for publishing, researchers can use this following link https://www.mystudywindow.com/msw/datasharing to request access to the clinical study documents regarding this study, and upon a signed "Document Sharing Agreement".

Also, Researchers can use the following link https://www.mystudywindow.com/msw/datasharing to find information in order to request access to the clinical study data, for this and other listed studies, after the submission of a research proposal and according to the terms outlined in the website.

The data shared are the raw clinical study data sets.

Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Clinical Study Report (CSR)
Time Frame: After all regulatory activities are completed in the US and EU for the product and indication, and after the primary manuscript has been accepted for publication.
Access Criteria: For study documents - upon signing of a 'Document Sharing Agreement'. For study data - 1. after the submission and approval of the research proposal (checks will be performed by both the independent review panel and the sponsor, including checking that the planned analysis does not compete with sponsor's publication plan); 2. and upon signing of a 'Data Sharing Agreement'.
URL: https://www.mystudywindow.com/msw/datasharing

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Respiratory Distress Syndrome, Newborn
Respiratory Distress Syndrome, Adult
Acute Lung Injury
Syndrome
Disease
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases
Respiration Disorders
Infant, Premature, Diseases
Infant, Newborn, Diseases
Lung Injury
Tissue Plasminogen Activator
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action