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

NCT04453371 | Withdrawn Phase 3 DMC

• 1 other identifier: tPA-2020
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Acute Respiratory Distress Syndrome

Keywords

COVID-19; MicroCLOTS; Atypical Acute Respiratory Distress Syndrome

Outcome Measures

Primary Outcomes (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.

  Each 6 hours during first 3 days after the end of thrombolysis procedure.

Secondary Outcomes (1)

• Ventilator-free time (days free from MV) for 28 days of observation.

  28 days

Other Outcomes (10)

• Mortality in 28 days and 1 year after randomization despite of the reason.

  28 days, 1 year after randomization

• Length of stay in the ICU

  28 days

• Length of stay in hospital

  28 days

Study Arms (2)

Study group

EXPERIMENTAL

Thrombolysis

Drug: Tissue plasminogen activator

Control group

PLACEBO COMPARATOR

Ringer's solution infusion

Drug: Ringer solution

Interventions

Tissue plasminogen activator DRUG

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.

Also known as: Alteplase

Study group

Ringer solution DRUG

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.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Severe pulmonary coronavirus disease 19 (COVID 19) with suspect for MicroCLOTS (microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome)
• P/F ratio \<200 mmHg\> 70 mmHg
• a.) Contrast CT scan positive for pulmonary thrombosis, OR b.) Contrast CT scan negative for pulmonary thrombosis:
• D-Dimer \> 10 mcg/mL, OR
• \< D-dimer \< 10 mcg/mL and C Reactive Protein (CRP) \> 100 mg/dL

You may not qualify if:

• 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).

Sponsors & Collaborators

• Negovsky Reanimatology Research Institute: lead
• Demikhov Municipal Clinical Hospital 68: collaborator

MeSH Terms

Conditions

Respiratory Distress Syndrome; COVID-19

Interventions

Tissue Plasminogen Activator; Ringer's Solution

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections

Intervention Hierarchy (Ancestors)

Serine Endopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Serine Proteases; Plasminogen Activators; Blood Coagulation Factors; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Biological Factors; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 26, 2020
• First Posted: July 1, 2020
• Study Start: October 15, 2020
• Primary Completion: January 15, 2021
• Study Completion: February 15, 2021
• Last Updated: March 12, 2021

Record last verified: 2021-03