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In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection

Primary Purpose

COVID-19

Status
Completed
Phase
Not Applicable
Locations
Mexico
Study Type
Interventional
Intervention
tPA
Sponsored by
Grupo Mexicano para el Estudio de la Medicina Intensiva
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for COVID-19 focused on measuring Covid-19, Acute Respiratory Distress Syndrome, Thrombosis

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:Lung criteria:

Patients with severe Covid 19 nfection, from 18 to 75 years old, Invasive Mechanical Ventilation (IMV) Pao2 / fio2 less than 150 Non réponse to prone position Coagulation criteria ISTH score >5, D-dimer greater than 1200, Viscoelastic testing EXTEM A5 >65 FIBTEM > 30 and EXTEM ML<8%

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Exclusion Criteria:

Ischemic CVD or presence of abnormal neurological examination. Active bleeding. Acute Myocardial Infarction within the previous three weeks or cardiac arrest during hospitalization.

cardiac tamponade. endocarditis. uncontrolled hypertension SBP> 185mmhg or DBP> 110. history of stage 4 cancer. history of brain tumor. Arterious venous malformation ruptured aneurysm. major surgery in the previous 2 weeks major trauma in the previous 2 weeks. pregnancy. fibrinogen less than 200 blood dyscrasias thrombocytopenia less than 30,000

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Sites / Locations

  • Hospital General de Mexico Dr Eduardo Liceaga

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

experimental arm

Arm Description

In situ thrombolysis with tPA

Outcomes

Primary Outcome Measures

Changes in lung perfusion
changes in contrast distribution comparing pre and post-thrombolysis using Iflow parameters that include ROI, peak flow and Time

Secondary Outcome Measures

Coagulation
changes in D Dimer, standard coagulation test and fibrinogen
Oxygenation Index
changes in PaO2/FiO2 index pre and post-thrombolysis

Full Information

First Posted
June 13, 2021
Last Updated
June 16, 2021
Sponsor
Grupo Mexicano para el Estudio de la Medicina Intensiva
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1. Study Identification

Unique Protocol Identification Number
NCT04926428
Brief Title
In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection
Official Title
In Situ Thrombolysis With tPA and Inflow Lung Perfusion Analysis in Patient With Severe Covid-19 Infection
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
December 25, 2020 (Actual)
Primary Completion Date
March 30, 2021 (Actual)
Study Completion Date
March 30, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Grupo Mexicano para el Estudio de la Medicina Intensiva

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To estimate the pulmonary response microvascular thrombosis in critical patients due to SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients compassionate treatment study was authorized and approved by the ethics and research committee DI-222-2020. Because of the severity of the illness the legal representative sign informed consent in all the patients for performing in-situ thrombolysis with alteplase selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and acquiring images with the iFlow software to assess immediate and post-procedure response.
Detailed Description
The main clinical characteristic of patients with severe SARS-Cov-2 infection is hypoxemic respiratory failure that requires Mechanical Ventilation. The Acute Respiratory Syndrome model has been proposed as the cause of this significant deterioration in lung function and all management has focused on ventilatory support management. As for ventilatory failure, it has been attributed to the presence of severe pulmonary inflammation evolving to fibrosis, which is the clinical characteristic of patients with Primary Respiratory Distress Syndrome (which would be the case of this as it is considered a respiratory virus). Several autopsy studies demonstrated microthrombi in pulmonary circulation. The major limitation of these investigations is that the autopsy provided static information. Some of these alterations could be secondary to the disseminated intravascular coagulation (DIC) observed as the standard route to the multisystem organ failure exhibited in critically ill patients. With this comes the contradictory results of high doses of anticoagulants in the survival of these patients. This intermediate to high doses can reduce organ support treatments in moderate cases, however, in critically ill patients the benefit of high dose of anticoagulants, once again failed to produce benefit on survival. Different publication on biopsies made in these patients have report the presence of thrombosis in the microcirculation and finally recently has been published the demonstration by direct examination with Citoscam, the presence of this thrombosis of the microcirculation in vivo in 11 of 13 test (85% of the sample). Studies performed with viscoelastic coagulation tests present evidence of three key alterations in coagulation EXTEM and INTEM Hypercoagulable states represented by a maximum amplitude (A5, A10 and MCF) greater than 70mm, short clot formation time. Hyperfibrinogenemia A5 A10 MCF in FIBTEM greater than 30mm Absence of fibrinolytic activity (ML% Lys 30 and Lys 60) 100% Taking this into account plus the large number of publications regarding the thrombotic phenomenon of the patient with COVID-19, this could be explained by the presence of a phenomenon of ventilation perfusion (V / Q) that is observed in patients with Massive Pulmonary Thromboembolism (PE) which is known as the infinite relationship, that is, the lung is with normal aeration, but no perfusion, there is no adequate gas exchange, with presence of hypoxia, increment of death space and ultimately obstructive shock. In patients with COVID-19, this phenomenon is observed in patients with absence of massive or submassive PE that explains this phenomenon. The high mortality of critically ill patients with SARS-Cov-2 infection, the presence of thrombosis of the microcirculation and the lack of efficacy of anticoagulation in some cases suggests that this phenomenon could be the cause of the behavior between perfusion ventilation observed in SARS-Cov-2 patients. For these reasons, a probe of concept research was developed to find out if pulmonary perfusion alteration by microthrombosis and secondary V / Q abnormalities could be linked to the pathophysiology of the patient with severe SARS-Cov-2 infection. To estimate the pulmonary response microvascular thrombosis in critical patients due to SARS-Cov-2., at the Hospital General de México "Dr. Eduardo Liceaga", a 15 patients compassionate treatment study was authorized and approved by the ethics and research committee DI-222-2020. Because of the severity of the illness the legal representative sign informed consent in all the patients for performing in-situ thrombolysis with alteplase selectively by catheter in each main pulmonary artery, under fluoroscopic guidance and acquiring images with the iFlow software to assess immediate and post-procedure response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19
Keywords
Covid-19, Acute Respiratory Distress Syndrome, Thrombosis

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
experimental arm
Arm Type
Experimental
Arm Description
In situ thrombolysis with tPA
Intervention Type
Drug
Intervention Name(s)
tPA
Other Intervention Name(s)
in situ thrombolysis
Intervention Description
Selectively catheter thrombolysis with alteplase in each main pulmonary
Primary Outcome Measure Information:
Title
Changes in lung perfusion
Description
changes in contrast distribution comparing pre and post-thrombolysis using Iflow parameters that include ROI, peak flow and Time
Time Frame
1 hour
Secondary Outcome Measure Information:
Title
Coagulation
Description
changes in D Dimer, standard coagulation test and fibrinogen
Time Frame
48 hours
Title
Oxygenation Index
Description
changes in PaO2/FiO2 index pre and post-thrombolysis
Time Frame
48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:Lung criteria: Patients with severe Covid 19 nfection, from 18 to 75 years old, Invasive Mechanical Ventilation (IMV) Pao2 / fio2 less than 150 Non réponse to prone position Coagulation criteria ISTH score >5, D-dimer greater than 1200, Viscoelastic testing EXTEM A5 >65 FIBTEM > 30 and EXTEM ML<8% - Exclusion Criteria: Ischemic CVD or presence of abnormal neurological examination. Active bleeding. Acute Myocardial Infarction within the previous three weeks or cardiac arrest during hospitalization. cardiac tamponade. endocarditis. uncontrolled hypertension SBP> 185mmhg or DBP> 110. history of stage 4 cancer. history of brain tumor. Arterious venous malformation ruptured aneurysm. major surgery in the previous 2 weeks major trauma in the previous 2 weeks. pregnancy. fibrinogen less than 200 blood dyscrasias thrombocytopenia less than 30,000 -
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jose Damian Carrillo Ruiz, PhD
Organizational Affiliation
Hospital General de Mexico Dr. Eduardo Liceaga
Official's Role
Study Director
Facility Information:
Facility Name
Hospital General de Mexico Dr Eduardo Liceaga
City
Mexico City
ZIP/Postal Code
06720
Country
Mexico

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
IPD will be shared by petition.
IPD Sharing Time Frame
3 months up to 5 years after completion
IPD Sharing Access Criteria
proposal should be directed to gmemiinv@gmails.com, to gain access, requestor will need to sign a data access agreement
Citations:
PubMed Identifier
3298679
Citation
Greene R. Pulmonary vascular obstruction in the adult respiratory distress syndrome. J Thorac Imaging. 1986 Jul;1(3):31-8. doi: 10.1097/00005382-198607000-00006.
Results Reference
background
PubMed Identifier
32172546
Citation
Yao XH, Li TY, He ZC, Ping YF, Liu HW, Yu SC, Mou HM, Wang LH, Zhang HR, Fu WJ, Luo T, Liu F, Guo QN, Chen C, Xiao HL, Guo HT, Lin S, Xiang DF, Shi Y, Pan GQ, Li QR, Huang X, Cui Y, Liu XZ, Tang W, Pan PF, Huang XQ, Ding YQ, Bian XW. [A pathological report of three COVID-19 cases by minimal invasive autopsies]. Zhonghua Bing Li Xue Za Zhi. 2020 May 8;49(5):411-417. doi: 10.3760/cma.j.cn112151-20200312-00193. Chinese.
Results Reference
background
PubMed Identifier
32181795
Citation
Livingston E, Bucher K. Coronavirus Disease 2019 (COVID-19) in Italy. JAMA. 2020 Apr 14;323(14):1335. doi: 10.1001/jama.2020.4344. No abstract available.
Results Reference
background
PubMed Identifier
3342622
Citation
Vesconi S, Rossi GP, Pesenti A, Fumagalli R, Gattinoni L. Pulmonary microthrombosis in severe adult respiratory distress syndrome. Crit Care Med. 1988 Feb;16(2):111-3. doi: 10.1097/00003246-198802000-00002.
Results Reference
background
PubMed Identifier
32211957
Citation
Ospina-Tascon GA, Bautista DF, Madrinan HJ, Valencia JD, Bermudez WF, Quinones E, Calderon-Tapia LE, Hernandez G, Bruhn A, De Backer D. Microcirculatory dysfunction and dead-space ventilation in early ARDS: a hypothesis-generating observational study. Ann Intensive Care. 2020 Mar 24;10(1):35. doi: 10.1186/s13613-020-00651-1.
Results Reference
background

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In Situ Thrombolysis With tPA and Inflow Perfusion Analysis in Patient With Severe Covid-19 Infection

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