A prospective randomized controlled trial to compare recombinant tissue-type plasminogen activator (rt-PA) and standard treatmentin in patients with ARDS induced by COVID-19
Comparing recombinant tissue-type plasminogen activator (rt-PA) and standard treatment in patients with ARDS induced by COVID-19.
Design
Randomized clinical trial with control group; Randomized by quadruple block method; with parallel group design; with blinded outcome assessment (single blind), phase 3 on 30 cases.
Settings and conduct
The study site is the Intensive Care Unit for COVID-19 patients at Shariati Hospital in Tehran
Participants/Inclusion and exclusion criteria
Inclusion criteria:
People referring to the hospital with symptoms of clinical stenosis syndrome such as: shortness of breath, fever, cough, hypoxia, imaging in favor of ARDS & hypoxia,Non-pregnant man or woman over 18 years of age, confirmation of COVID-19 by PCR with imaging findings
Non-inclusion criteria:
Patient dissatisfaction, Bleeding tendency ,Previous hypersensitivity to Alteplase , Active internal bleeding , Severe uncontrolled hypertension, Severe renal disease (GFR<50 ml/min).
Intervention groups
Intervention group: Altplas 50 mg intravenously up to 0.9 mg per kg body weight in addition to the national treatment protocol of COVID-19 plus subcutaneous injection of Anaxaparin 1 mg per kg (15 patients).
Control group: COVID-19 treatment protocol plus subcutaneous injection of enoxaparin1 mg per kg bid (15 patients).
A prospective randomized controlled trial to compare recombinant tissue-type plasminogen activator (rt-PA) and standard treatmentin in patients with ARDS induced by COVID-19
Public title
Effectiveness of Tissue plasminogen activator (TPA) for treatment of ARDS induced by Covid-19
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
A person with laboratory confirmation of COVID-19 infection
clinical and radiological confirmation of ARDS
The confirm case of covid-19 in patients with ARDS (PaO2/FiO2a ≤ 300 or sat o2≤ 315 mmHg (with PEEP or CPAP ≥ 5 cmH2O, or non-ventilated)
Exclusion criteria:
Bleeding tendency
Coagulopathy (INR>1.5)
Thrombocytopenia (plt< 50000)
Previous hypersensitivity to Alteplase
Active internal bleeding
Severe uncontrolled hypertension
Severe renal disease (GFR<50 ml/min)
History of recent stroke
Hemoptysis at admission
Presence of any active malignancy (other than non-melanoma skin cancer) that required treatment within the last 2 years
Moderate to severe liver failure (Childs-Pugh Score > 12)
Major trauma in the prior 30 days
Moribund patient not expected to survive the next 24 hours.
No consent/inability to obtain consent
Age
From 18 years old to 70 years old
Gender
Both
Phase
3
Groups that have been masked
No information
Sample size
Target sample size:
30
Randomization (investigator's opinion)
Randomized
Randomization description
Patients are randomly assigned to one of the intervention or control groups by quadruple block method. After determining the volume of each block, the letter A is considered for the intervention group and the letter B for the control group. All permutation combinations of the letters A, A, B and B, which are 6 different combinations, are written on 6 cards and a digit is randomly selected from the digits 1 to 6. For example, if the number 2 is selected, it means that the first person in the intervention group, the next two people in the control group and the fourth person in the intervention group and continue until the sample size reaches the quorum.
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Ethics Committee of Tehran University of Medical Sciences
Street address
Dr. Shariati Hospital, Jalal Al-Ahmad Highway
City
Tehran
Province
Tehran
Postal code
1411713135
Approval date
2020-03-23, 1399/01/04
Ethics committee reference number
IR.TUMS.VCR.REC.1399.025
Health conditions studied
1
Description of health condition studied
COVID-19
ICD-10 code
U07.1
ICD-10 code description
COVID-19 induced ARDS
Primary outcomes
1
Description
The difference of PaO2/FiO2 or S/F ratio between two groups [ Time Frame: 72 h after randomization
Timepoint
24 Hours from treatment till 72 h
Method of measurement
measurement of S/F ratio or Po2?Fio2 with pulseoxymetry or Arterial Blood gas (ABG)
2
Description
Disease severity
Timepoint
day 3,7, 14,28
Method of measurement
WHO 8-score ordinal scale
3
Description
survival in patients with ARDS
Timepoint
28 day after treatment
Method of measurement
observation of patients status
4
Description
Time to Ventilator Free state
Timepoint
from treatment time to two weeks
Method of measurement
counting the days
5
Description
Adverse Drug Reaction after tratment
Timepoint
Daily
Method of measurement
patient status observation and lab data monitoring
Secondary outcomes
1
Description
Evaluation of ARDS mortality from COVID-19
Timepoint
From the time of admitted in the intensive care unit to the time of death
Method of measurement
Informed in clinical file
2
Description
Evaluation of hospital discharge status of patients with ARDS caused by COVID-19
Timepoint
From the time of admitted in the intensive care unit to the time of discharge
Method of measurement
Informed in clinical file
Intervention groups
1
Description
Intervention group: 15 cases : A-Alteplase (TPA) 25-50 mg ( half of the maximum dose 0.9 / kg /day) over 2 hours intravenous continuing by 25-50 /22 hours up to maximum dose of 0.9 mg/kg/d. This tPA injection may be repeated for 2 days and the patient's condition (PT level PTT, SPO2 and D- dimer) is observed and checked. After the end of TPA injection, subcutaneous injection of Enoxaparin will be started as 1 mg per kilogram body weight for the patient. Enoxaparin could be continued up to 7 days upon the condition of the patient. The patients will receive regular care and treatment for COVID-19 induced ARDS.
Category
Treatment - Drugs
2
Description
Control group: They will take routine treatment approved by the Ministry of Health for patients with adult respiratory distress from COVID 19,Also the subcutaneous injection of Enaxaparin one mg per kilogram of body weight for the patient added to their treatment .
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Shariati Hospital affiliated to Tehran University of Medical Sciences
Full name of responsible person
Rasoul Aliannejad
Street address
Shariati hospital,Jalal Al-Ahmad three ways, North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Fax
+98 21 8863 3039
Email
aliannejad@tums.ac.ir
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Mohhamad Ali Sahraian
Street address
Office of the Vice Chancellor for Research, North Door of the University, Building No. 1 of the Faculty of Medicine, Poursina street, Ghods street, Enghelab street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 1000
Fax
+98 21 8490 2871
Email
shariatihosp@tums.ac.ir
Web page address
Grant name
Tissue plasminogen activator for treatment of ARDS induced by Coronavirus infection, A Phase 1/2 clinical trial study
Grant code / Reference number
47125-101-1-99
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Tehran University of Medical Sciences
Proportion provided by this source
100
Public or private sector
Public
Domestic or foreign origin
Domestic
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
Academic
Person responsible for general inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rasoul Aliannejad
Position
Professor at Tehran University of Medical Sciences
Latest degree
Subspecialist
Other areas of specialty/work
Medical Education
Street address
Shariati hospital,Jalal Al-Ahmad three ways,North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 2260
Email
aliannejad@tums.ac.ir
Person responsible for scientific inquiries
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rasoul Aliannejad
Position
Professor
Latest degree
Subspecialist
Other areas of specialty/work
Medical Education
Street address
Jalal Al-Ahmad three ways; North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 2260
Email
aliannejad@tums.ac.ir
Person responsible for updating data
Contact
Name of organization / entity
Tehran University of Medical Sciences
Full name of responsible person
Rasoul Aliannejad
Position
Professor
Latest degree
Subspecialist
Other areas of specialty/work
Medical Education
Street address
Jalal Al-Ahmad three ways; North Kargar street
City
Tehran
Province
Tehran
Postal code
1411713135
Phone
+98 21 8490 2260
Email
aliannejad@tums.ac.ir
Sharing plan
Deidentified Individual Participant Data Set (IPD)
Undecided - It is not yet known if there will be a plan to make this available
Study Protocol
Undecided - It is not yet known if there will be a plan to make this available
Statistical Analysis Plan
Undecided - It is not yet known if there will be a plan to make this available
Informed Consent Form
Undecided - It is not yet known if there will be a plan to make this available
Clinical Study Report
Undecided - It is not yet known if there will be a plan to make this available
Analytic Code
Undecided - It is not yet known if there will be a plan to make this available
Data Dictionary
Undecided - It is not yet known if there will be a plan to make this available