UMIN-CTR Clinical Trial

Public title

The mechanism of COVID-19 associated coagulopathy: a prospective cohort study

Acronym

A prospective study of COVID-19 associated coagulopathy

Scientific Title

Circulating microparticles as biomarkers in COVID-19 associated coagulopathy: a prospective cohort study

Scientific Title:Acronym

The role of microparticles in coagulopathy of COVID-19: a prospective cohort study

Region

Japan

Condition

Patients admitted with COVID-19

Classification by specialty

Hematology and clinical oncology	Infectious disease	Intensive care medicine
Adult

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To clarify the origin of MPs, circulating MPs levels, and the role of MPs in coagulopathy of COVID-19

Basic objectives2

Bio-availability

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

The level of Tissue factor bearing microparticles

Key secondary outcomes

Study type

Observational

Basic design

Randomization

Randomization unit

Blinding

Control

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

Purpose of intervention

Type of intervention

Interventions/Control_1

Interventions/Control_2

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

120

years-old

>=

Gender

Male and Female

Key inclusion criteria

Patients admitted with COVID-19

Key exclusion criteria

(1) patients in which informed consent could not be obtained from the person or close relatives
(2) patients who have other infectious diseases
(3) patients with end-stage heart failure( defined as NYHA class4)
(4) patients with end-stage liver failure (defined as Child-Pugh classification C)
(5) patients with progressive cancer, or patients undergoing cancer treatment
(6) patients who are pregnant
(7) patients who have participated in this study
(8) patients who are diagnosed as COVID-19 accidentally and need emergency treatment for other diseases

Target sample size

100

Name of lead principal investigator

1st name	Koji
Middle name
Last name	Saito

Organization

Tohoku university hospital

Division name

Department of Intensive Care Unit

Zip code

980-8574

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi Japan

TEL

0227177000

Email

koji.saito.e1@tohoku.ac.jp

Name of contact person

1st name	Yudai
Middle name
Last name	Iwasaki

Organization

Tohoku university hospital

Division name

Department of Anesthesiology and Perioperative Medicine

Zip code

980-8574

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi Japan

TEL

0227177000

Homepage URL

Email

yudai.i0213@gmail.com

Institute

Tohoku university

Institute

Department

Personal name

Organization

Japan Agency for Medical Research and Development

Organization

Division

Category of Funding Organization

Japanese Governmental office

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Tohoku university hospital

Address

1-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi Japan

Tel

0227177000

Email

med-kenkyo@grp.tohoku.ac.jp

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2020

Year

12

Month

10

Day

URL releasing protocol

https://www.mdpi.com/2077-0383/12/10/3460

Publication of results

Published

URL related to results and publications

https://www.mdpi.com/2077-0383/12/10/3460

Number of participants that the trial has enrolled

99

Results

No difference was found in the EV levels between the non-coagulopathy and coagulopathy groups.We conducted three group comparison, COVID-19 coagulopathy group, non-coagulopathy group, and healthy volunteer. In the Kruskal Wallis test, the CD41 positive EV levels were statistically different among the groups. The coagulopathy group had higher CD41 positive EV levels than the healthy volunteer group.

Results date posted

2023

Year

06

Month

13

Day

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Age, dementia at admission, Charlson Comorbidity Index, and several laboratory findings, such as white blood cell counts, lactate dehydrogenase level, total protein level, albumin level, blood urea nitrogen level, C-reactive protein level, and fibrinogen level differed between the two groups. The coagulopathy group required oxygenation therapy at admission; this finding indicated that the disease severity in this group was higher than that in the non-coagulopathy group. Moreover, the coagulopathy group had worse clinical progression and a higher mortality rate than the non-coagulopathy group.

Participant flow

Patients aged 20 years or more who were diagnosed with COVID-19 and required hospitalization were included in this study. The diagnosis was made using a polymerase chain reaction, antigen test, or loop-mediated isothermal amplification. Meanwhile, patients who did not provide consent or whose close relatives did not provide consent; patients with other infections in addition to COVID-19; patients with end-stage heart failure defined as class IV according to the New York Heart Association Functional Classification , end-stage liver failure defined as Child-Pugh classification C , and any malignancy undergoing treatment; pregnant women; patients on their second admission for COVID-19; and patients accidentally diagnosed with COVID-19 through investigations of diseases requiring emergency therapeutic interventions were excluded.
Healthy volunteers were recruited from Tohoku University Hospital. Five healthy men and five healthy women aged 20 years and older with no chronic diseases requiring regular medication, with a body mass index of <30 kg/m2, with no history of smoking, with no history of COVID-19, and who were not pregnant during the study comprised the healthy volunteer group.
From November 2020 to April 2021, 110 COVID-19 patients were enrolled. Of these, 10 patients declined to participate; thus, 100 patients were initially included. As the information on the D-dimer level of 1 patient was missing, 99 were included in the final analysis. This cohort was divided into two groups based on the D-dimer levels. In total, 51 and 48 patients were enrolled in the non-coagulopathy and coagulopathy groups, respectively. In the same study period, 10 healthy controls were evaluated for EV detection.

Adverse events

not applicable

Outcome measures

We postulated that COVID-19 coagulopathy would be associated with an increase in EV levels. However, before this study, no evidence was available on the association between EV levels and COVID-19 coagulopathy. Therefore, we conducted a preliminary study to confirm our hypothesis by comparing several EV levels between a healthy volunteer group and the first 10 patients from the coagulopathy group. Next, we compared the EV levels between the COVID-19 coagulopathy and non-coagulopathy groups. Due to the exploratory nature of our research and the need to detect EVs linked to coagulopathy, we examined the levels of multiple EV types.
The primary endpoint was the difference in levels of TF-bearing EVs between the coagulopathy and non-coagulopathy groups, while the secondary outcomes were the levels of other types of EVs. In addition to TF-bearing EVs, we measured the levels of endothelium-derived EVs, platelet-derived EVs, monocyte-derived EVs, and neutrophil-derived EVs as the target EVs. We also measured the levels of each EV combined with TF.

Plan to share IPD

IPD sharing Plan description

Recruitment status

Completed

Date of protocol fixation

2020

Year

10

Month

03

Day

Date of IRB

2020

Year

10

Month

28

Day

Anticipated trial start date

2020

Year

11

Month

09

Day

Last follow-up date

2021

Year

09

Month

30

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

2022

Year

08

Month

31

Day

Other related information

We are going to evaluate whether microparticles(MPs) are associated with COVID-19 associated coagulopathy. We will collect blood from COVID-19 patients and measure MPs levels. And we assess whether COVID-19 coagulopathic patients have statistically higher MPs levels compared with COVID-19 non-coagulopathic patients.

Registered date

2020

Year

12

Month

10

Day

Last modified on

2023

Year

06

Month

13

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000048021