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Impact of Tissue Plasminogen Activator (tPA) Treatment for an Atypical Acute Respiratory Distress Syndrome (COVID-19) (AtTAC)

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ClinicalTrials.gov Identifier: NCT04453371
Recruitment Status : Withdrawn (Our local committee has denied the approval request)
First Posted : July 1, 2020
Last Update Posted : March 12, 2021
Sponsor:
Collaborator:
Demikhov Municipal Clinical Hospital 68
Information provided by (Responsible Party):
Negovsky Reanimatology Research Institute

Brief Summary:
At the beginning COVID-associated lung injury was considered as typical ARDS, hence respiratory and nonrespiratory treatments were delivered according to general principles for this kind of illness. There is hypothesis that in predisposed individuals, alveolar viral damage is followed by an inflammatory reaction and by microvascular pulmonary thrombosis. The investigators suggest that thrombolytic therapy may be beneficial when compared to standard care in patients with SARS-CoV-2 and severe respiratory failure.

Condition or disease Intervention/treatment Phase
Acute Respiratory Distress Syndrome Drug: Tissue plasminogen activator Drug: Ringer solution Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Primary Purpose: Treatment
Official Title: Tissue Plasminogen Activator (tPA) Treatment for an Atypical Acute Respiratory Distress Syndrome (Microvascular COVID-19 Lung Vessels Obstructive Thromboinflammatory Syndrome (MicroCLOTS): A Multicentral Randomized Trial (AtTAC-trial)
Estimated Study Start Date : October 15, 2020
Estimated Primary Completion Date : January 15, 2021
Estimated Study Completion Date : February 15, 2021


Arm Intervention/treatment
Experimental: Study group
Thrombolysis
Drug: Tissue plasminogen activator

In the study group, tPA (Alteplase) 25 mg i/v over 2 hours, followed by a 25 mg tPA infusion over the subsequent 22 hours. After the end of thrombolytic therapy, unfractionated heparin is administered i/v at a starting dose of 10 units / kg per hour. The target value of PTT is 40C-50C.

In both groups patient's transfer from the heparin infusion to the introduction of low-molecular-weight heparins is performed after normalization of the D-dimer level.

Other Name: Alteplase

Placebo Comparator: Control group
Ringer's solution infusion
Drug: Ringer solution

In the control group, an equivalent amount of Ringer's solution is administered. After 24 hours, the heparin infusion gets started, similar the described for study group.

In both groups patient's transfer from the heparin infusion to the introduction of low-molecular-weight heparins is performed after normalization of the D-dimer level.





Primary Outcome Measures :
  1. P/F (PaO2/FiO2) change during the first 72hrs after the end of the procedure in adult patients with severe atypical ARDS caused by SARS-2-CoV. [ Time Frame: Each 6 hours during first 3 days after the end of thrombolysis procedure. ]

Secondary Outcome Measures :
  1. Ventilator-free time (days free from MV) for 28 days of observation. [ Time Frame: 28 days ]
    Calculated as 28 days - number of days when patient receive any kind of ventilatory support (MV + SV + NIV).


Other Outcome Measures:
  1. Mortality in 28 days and 1 year after randomization despite of the reason. [ Time Frame: 28 days, 1 year after randomization ]
  2. Length of stay in the ICU [ Time Frame: 28 days ]
    Number of days when patient was in ICU

  3. Length of stay in hospital [ Time Frame: 28 days ]
    Number of days when patient was in hospital

  4. The time needed for "improvement of 2 points" according to WHO "Ordinal Scale for Clinical Improvement" [ Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 1 month ]
  5. Chest radiographs on a daily basis and define barotrauma as the presence of new pneumothorax, pneumomediastinum, pneumoperitoneum, or subcutaneous emphysema. [ Time Frame: Daily up to extubation than once a week/or on attending intensivist's discretion up to 1 month ]
  6. Blood Pressure in millimetres of mercury [ Time Frame: Each 4 hours during first 2 weeks after the end of thrombolysis procedure. ]
  7. Heart Rate in beats per minute [ Time Frame: Each 4 hours during first 2 weeks after the end of thrombolysis procedure. ]
  8. Blood Oxygen Saturation [ Time Frame: Each 4 hours during first 2 weeks after the end of thrombolysis procedure. ]
  9. ECG Q-wave [ Time Frame: Each 24 hours during first 2 weeks after the end of thrombolysis procedure. ]
  10. ECG ST-segment [ Time Frame: Each 24 hours during first 2 weeks after the end of thrombolysis procedure. ]


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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:

  1. Severe pulmonary coronavirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome)
  2. P/F ratio <200 mmHg> 70 mmHg
  3. a.) Contrast CT scan positive for pulmonary thrombosis, OR b.) Contrast CT scan negative for pulmonary thrombosis:

    • D-Dimer > 10 mcg/mL, OR
    • 5 < D-dimer < 10 mcg/mL and C Reactive Protein (CRP) > 100 mg/dL

Exclusion Criteria:

  • Age < 18
  • Pregnancy or breastfeeding
  • Known allergy to iodinated contrast dye
  • Severe vasoplegic shock: norepinephrine > 300 ng/kg*min
  • Glomerular Filtration rate < 30 ml/min
  • Active bleeding or absolute contraindication to anticoagulant therapy (Stroke (intracranial hemorrhage, hemorrhagic stroke), including a history of the last 6 months.; cancer of the Central nervous system and other localities with an increased risk of bleeding, vascular aneurysm, traumatic open heart massage, obstetric delivery, General operations, severe uncontrolled hypertension, gastric ulcer and 12-duodenal ulcer (for 3 months. from the moment of exacerbation), arterial or venous malformations, liver failure, liver cirrhosis, portal hypertension, esophageal varicose veins, active hepatitis).
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Responsible Party: Negovsky Reanimatology Research Institute
ClinicalTrials.gov Identifier: NCT04453371    
Other Study ID Numbers: tPA-2020
First Posted: July 1, 2020    Key Record Dates
Last Update Posted: March 12, 2021
Last Verified: March 2021

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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 Negovsky Reanimatology Research Institute:
COVID-19
MicroCLOTS
Atypical Acute Respiratory Distress Syndrome
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
Plasminogen
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action