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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 : September 10, 2021
Sponsor:
Information provided by (Responsible Party):
Boehringer Ingelheim

Tracking Information
First Submitted Date  ICMJE November 20, 2020
First Posted Date  ICMJE November 23, 2020
Last Update Posted Date September 10, 2021
Actual Study Start Date  ICMJE December 16, 2020
Estimated Primary Completion Date May 13, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: November 23, 2020)
  • All cause mortality [ Time Frame: At day 28 ]
  • Number of ventilator-free days [ Time Frame: From start of treatment to day 28 ]
  • 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.
  • Number of major bleeding events (MBE) [ Time Frame: Up to day 6 ]
    according to International Society on Thrombosis and Haemostasis (ISTH) definition
  • 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
  • All-cause mortality or on mechanical ventilation [ Time Frame: At day 28 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: November 20, 2020)
  • All cause mortality [ Time Frame: At day 28 ]
  • Number of ventilator-free days [ Time Frame: From start of treatment to day 28 ]
  • 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.
  • Number of major bleeding events (MBE) [ Time Frame: Up to day 6 ]
    according to International Society on Thrombosis and Haemostasis [ISTH] definition
  • 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
  • All-cause mortality or on mechanical ventilation [ Time Frame: At day 28 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study to Test Whether Different Doses of Alteplase Help People With Severe Breathing Problems Because of COVID-19
Official Title  ICMJE 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
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE 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
Condition  ICMJE Acute Respiratory Distress Syndrome
Intervention  ICMJE
  • 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.
Study Arms  ICMJE
  • Control group
    Standard of care alone
    Intervention: Procedure: Standard of care
  • Experimental: Treatment group A
    Alteplase (low dose) on top of standard of care
    Interventions:
    • Drug: Alteplase
    • Procedure: Standard of care
  • Experimental: Treatment group B
    Alteplase (high dose) on top of standard of care
    Interventions:
    • Drug: Alteplase
    • Procedure: Standard of care
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: November 20, 2020)
270
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 15, 2022
Estimated Primary Completion Date May 13, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Boehringer Ingelheim 1-800-243-0127 clintriage.rdg@boehringer-ingelheim.com
Listed Location Countries  ICMJE Austria,   Belgium,   Brazil,   Denmark,   France,   Germany,   Italy,   Netherlands,   Portugal,   Russian Federation,   Spain
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04640194
Other Study ID Numbers  ICMJE 0135-0347
2020-002913-16 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
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
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: 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
Responsible Party Boehringer Ingelheim
Study Sponsor  ICMJE Boehringer Ingelheim
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Boehringer Ingelheim
Verification Date September 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP