Covid19iGenes-COVID19NCT04519398
Investigating the Involvement of ACE and Angiotensinogen Genes' Polymorphism Along With Other Thrombophilic Genotypes in Severe Forms of COVID-19 With/Without Thrombotic Events
An observational study of Covid19 and Corona Virus Infection, run by Grigore T. Popa University of Medicine and Pharmacy at 1 site in Romania.
Trial summary
An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Covid19, Corona Virus Infection, Thrombosis
- What is being tested?
- Complete thrombophilic profile testing by multiplex PCR
- How many people
- 60 participants
- Where
- 1 siteRomania
- Study dates
- 18 Aug 2020to 18 Aug 2021
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients with COVID-19 and thrmbotic events or, Patients with COVID-19 \& no thrombotic events but with a severe form Patients with COVID-19 \& no thrombotic events and no or mild symptoms
Who may be able to join
- All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test
Who cannot join
- Patient refusal
- Uncertain tests results
- Children
Trial locations and contacts
1 site in 1 country.
Radu Crisan-Dabija, MD, PhD contact
Romania1 site, 1 recruiting
- Recruiting
University of Medicine and Pharmacy Gr T. Popa Iasi, Romania
Iași, 700503
Adrian Covic, Professor, accovic@gmail.com
Radu Crisan-Dabija, Lecturer, radu.dabija@umfiasi.ro
About this study
An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. A major public health question remains to be investigated: why COVID-19 is mild for some, critically severe for others and why only a percentage of COVID-19 patients develop thrombosis, despite the disease's proven hypercoagulable state? Patients' intrinsic characteristics might be responsible for the deep variety of disease forms.
Our study aims to assess the validity of the hypothesis according to which underlining genetic variations might be responsible for different degrees of severity and thrombotic events risks in the novel coronavirus disease.
Read more
Moreover, we suspect that prothrombotic genotypes occuring in the genes that encode angiotensin-converting enzyme (ACE-DEL/INS) and angiotensinogen (AGT M235T) are involved in the unpredictable evolution of COVID-19, both in terms of severity and thrombotic events, due to the strong interactions of SARS-CoV-2 with the renin-angiotensin-aldosterone system (RAAS). Therefore, we also aim to assess the validity of the theory according to which there is a pre-existing atypical modulation of RAAS in COVID-19 patients that develop severe forms and/or thrombosis.
Our hypothesis is based on various observations. Firstly, there is a substantial similarity with a reasonably related condition such as sepsis, for which there is a validated theory stating that thrombophilic mutations affect patients' clinical response. Secondly, racial and ethnic genetic differences are responsible for significant dissimilar thrombotic risks among various nations. Thirdly, an increase in stroke incidence has been reported in young patients with COVID-19, without essential thrombosis risk factors, favoring the idea that a genetic predisposition could contribute to increase the thrombotic and thromboembolic risk. Fourthly, the plasminogen activator inhibitor (PAI)-1 4G/5G inherited mutation was found to be responsible for a thrombotic state causing post-SARS osteonecrosis.
Read the detailed description
The study's protocol will cover the following steps:
- Collected data from COVID-19 patients at admission will include:
- Descriptive general demographic data
- Previous pathologies and thrombosis risk factors
- Routine biological data (the blood routinely collected will also be used for SARS-Cov-2 specific RT-PCR exam)
Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes:
- Factor V Leiden
- Factor V 4070 A G (Hr2)
- Factor II G20210A
- Methylenetetrahydrofolate reductase (MTHFR) C677T
- MTHFR A1298C
- Cystathionine β-synthase (CBS) 844ins68
- PAI-1 4G/5G
- Glycoprotein IIIa T1565C (HPA-1a/b)
- ACE-DEL/INS
- Apolipoprotein E (ApoE)
- AGT M235T
- Angiotensin II type 1 receptor (ATR-1) A1166C
- Fibrinogen - 455 G A
- Factor XIII Val34Leu SpO2, respiratory rate, PaO2/FiO2 RAAS components
- Imagistic procedures (chest X-ray or CT)
- All patients with a positive SARS-CoV-2 PCR test will be included
- Patients will be divided into three groups depending on disease severity and the presence of thrombotic state:
- 1st group includes COVID-19 patients with proved
- venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms)
- or arterial thrombosis (heart attacks, strokes)
- 2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 ≥ 94%
- 3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50%
- Statistical methods will be employed to check for significant differences between prothrombotic mutations frequency and RAAS components levels for the three groups
- Conditions
- Covid19, Corona Virus Infection, Thrombosis, ARDS, Thrombophilia, Thromboses, Intracranial
- Being tested
- Complete thrombophilic profile testing by multiplex PCR
- Keywords
- Covid-19, COVID-19 severity, Thrombosis, Thrombophilia, thrombophylic profile, Renin-angiotensin-aldosterone system alterations
- Medical subject headings
- COVID-19, Coronavirus Infections, Thrombosis, Thrombophilia, Intracranial Thrombosis, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Complete thrombophilic profile testing by multiplex PCRGenetic
Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes:
- Factor V Leiden
- Factor V 4070 A>G (Hr2)
- Factor II G20210A
- Methylenetetrahydrofolate reductase (MTHFR) C677T
- MTHFR A1298C
- Cystathionine β-synthase (CBS) 844ins68
- PAI-1 4G/5G
- Glycoprotein IIIa T1565C (HPA-1a/b)
- ACE-DEL/INS
- Apolipoprotein E (ApoE)
- AGT M235T
- Angiotensin II type 1 receptor (ATR-1) A1166C
- Fibrinogen - 455 G>A
- Factor XIII Val34Leu
| Study group | Role | What they receive |
|---|---|---|
| COVID-19 patients with proved venous thrombosis | 1st group includes COVID-19 patients with proved
* venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms)
* or arterial thrombosis (heart attacks, strokes) Receives: Genetic: Complete thrombophilic profile testing by multiplex PCR | |
| Asymptomatic COVID-19 & those with mild or moderate disease | 2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 > 94% Receives: Genetic: Complete thrombophilic profile testing by multiplex PCR | |
| Severe disease, according to Guidelines, without thrombus | 3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50% Receives: Genetic: Complete thrombophilic profile testing by multiplex PCR |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of patients with thrombophilic profile alterations
The difference of prothrombotic genotypes frequency between the three groups
Measured: One year
Secondary outcomes (1)
Number of patients with RAAS components alterations
The differences of RAAS components levels between the three groups
Measured: One year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Aug 2020
- Study start18 Aug 2020
- Primary completion17 Feb 2021 (estimated)
- Study completion18 Aug 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Covid19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Ecologic or community
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Grigore T. Popa University of Medicine and Pharmacy
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Professor Adrian Covic, Grigore T. Popa University of Medicine and Pharmacy
- Investigators
- Adrian Covic, Professor, Study chair, Gr T Popa University of Medicine and Pharmacy Iasi ROMANIA
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04519398
- Sponsor's protocol ID
- GTP0051
- Acronym
- iGenes-COVID19
- Status last verified
- Aug 2020
- First submitted
- 18 Aug 2020
- Last updated
- 19 Aug 2020
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 19 Aug 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Investigating the Involvement of ACE and Angiotensinogen Genes' Polymorphism Along With Other Thrombophilic Genotypes in Severe Forms of COVID-19 With/Without Thrombotic Events
- ClinicalTrials.gov ID
- NCT04519398
- Acronym / sponsor ID
- iGenes-COVID19 / GTP0051
- Conditions
- Covid19, Corona Virus Infection, Thrombosis, ARDS, Thrombophilia, Thromboses, Intracranial
- Keywords
- Covid-19, COVID-19 severity, Thrombosis, Thrombophilia, thrombophylic profile, Renin-angiotensin-aldosterone system alterations
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Grigore T. Popa University of Medicine and PharmacyUniversity, hospital or other
- Study start
- 18 Aug 2020 (actual)
- Primary completion
- 17 Feb 2021 (estimated)
- Study completion
- 18 Aug 2021 (estimated)
- First posted
- 19 Aug 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
An estimated 22% of the global population is at an increased risk of a severe form of COVID-19, while one in four coronavirus patients admitted to intensive care unit will develop a pulmonary embolism. A major public health question remains to be investigated: why COVID-19 is mild for some, critically severe for others and why only a percentage of COVID-19 patients develop thrombosis, despite the disease's proven hypercoagulable state? Patients' intrinsic characteristics might be responsible for the deep variety of disease forms.
Our study aims to assess the validity of the hypothesis according to which underlining genetic variations might be responsible for different degrees of severity and thrombotic events risks in the novel coronavirus disease.
Moreover, we suspect that prothrombotic genotypes occuring in the genes that encode angiotensin-converting enzyme (ACE-DEL/INS) and angiotensinogen (AGT M235T) are involved in the unpredictable evolution of COVID-19, both in terms of severity and thrombotic events, due to the strong interactions of SARS-CoV-2 with the renin-angiotensin-aldosterone system (RAAS). Therefore, we also aim to assess the validity of the theory according to which there is a pre-existing atypical modulation of RAAS in COVID-19 patients that develop severe forms and/or thrombosis.
Our hypothesis is based on various observations. Firstly, there is a substantial similarity with a reasonably related condition such as sepsis, for which there is a validated theory stating that thrombophilic mutations affect patients' clinical response. Secondly, racial and ethnic genetic differences are responsible for significant dissimilar thrombotic risks among various nations. Thirdly, an increase in stroke incidence has been reported in young patients with COVID-19, without essential thrombosis risk factors, favoring the idea that a genetic predisposition could contribute to increase the thrombotic and thromboembolic risk. Fourthly, the plasminogen activator inhibitor (PAI)-1 4G/5G inherited mutation was found to be responsible for a thrombotic state causing post-SARS osteonecrosis.
Detailed description
The study's protocol will cover the following steps:
- Collected data from COVID-19 patients at admission will include:
- Descriptive general demographic data
- Previous pathologies and thrombosis risk factors
- Routine biological data (the blood routinely collected will also be used for SARS-Cov-2 specific RT-PCR exam)
Complete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes:
- Factor V Leiden
- Factor V 4070 A G (Hr2)
- Factor II G20210A
- Methylenetetrahydrofolate reductase (MTHFR) C677T
- MTHFR A1298C
- Cystathionine β-synthase (CBS) 844ins68
- PAI-1 4G/5G
- Glycoprotein IIIa T1565C (HPA-1a/b)
- ACE-DEL/INS
- Apolipoprotein E (ApoE)
- AGT M235T
- Angiotensin II type 1 receptor (ATR-1) A1166C
- Fibrinogen - 455 G A
- Factor XIII Val34Leu SpO2, respiratory rate, PaO2/FiO2 RAAS components
- Imagistic procedures (chest X-ray or CT)
- All patients with a positive SARS-CoV-2 PCR test will be included
- Patients will be divided into three groups depending on disease severity and the presence of thrombotic state:
- 1st group includes COVID-19 patients with proved
- venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms)
- or arterial thrombosis (heart attacks, strokes)
- 2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 ≥ 94%
- 3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50%
- Statistical methods will be employed to check for significant differences between prothrombotic mutations frequency and RAAS components levels for the three groups
Study design
- Observational model
- Ecologic or community
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| COVID-19 patients with proved venous thrombosis | – | Genetic: Complete thrombophilic profile testing by multiplex PCR1st group includes COVID-19 patients with proved * venous thrombosis (deep vein thrombosis, pulmonary embolism or venous thrombosis occurring in more atypical places such as in the veins of the brain, liver, kidney, mesenteric vein and the veins of the arms) * or arterial thrombosis (heart attacks, strokes) |
| Asymptomatic COVID-19 & those with mild or moderate disease | – | Genetic: Complete thrombophilic profile testing by multiplex PCR2nd group encompasses asymptomatic patients and those with mild or moderate disease, according to current guidelines, without thrombosis: no symptoms or evidence of lower respiratory disease by clinical assessment or imaging and a SpO2 > 94% |
| Severe disease, according to Guidelines, without thrombus | – | Genetic: Complete thrombophilic profile testing by multiplex PCR3rd group includes severe disease, according to current guidelines, without thrombosis: respiratory frequency > 30 breaths per minute, SpO2 < 94%, PaO2/FiO2 < 300 mmHg, or lung infiltrates >50% |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients with COVID-19 and thrmbotic events or, Patients with COVID-19 \& no thrombotic events but with a severe form Patients with COVID-19 \& no thrombotic events and no or mild symptoms
Key inclusion criteria (1 listed)
- All hospitalized patients with cough, fever, myalgia - with confirmed COVID-19 infection • All patients with a positive SARS-CoV-2 PCR test
Key exclusion criteria (3 listed)
- Patient refusal
- Uncertain tests results
- Children
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Complete thrombophilic profile testing by multiplex PCRComplete thrombophilic profile testing by multiplex PCR and reverse hybridization of DNA to assess the presence of prothrombotic genotypes: * Factor V Leiden * Factor V 4070 A>G (Hr2) * Factor II G20210A * Methylenetetrahydrofolate reductase (MTHFR) C677T * MTHFR A1298C * Cystathionine β-synthase (CBS) 844ins68 * PAI-1 4G/5G * Glycoprotein IIIa T1565C (HPA-1a/b) * ACE-DEL/INS * Apolipoprotein E (ApoE) * AGT M235T * Angiotensin II type 1 receptor (ATR-1) A1166C * Fibrinogen - 455 G>A * Factor XIII Val34Leu | Genetic | Asymptomatic COVID-19 & those with mild or moderate disease, COVID-19 patients with proved venous thrombosis, Severe disease, according to Guidelines, without thrombus |
Primary outcome
Number of patients with thrombophilic profile alterations
Time frame: One year
The difference of prothrombotic genotypes frequency between the three groups
1 secondary outcome
Number of patients with RAAS components alterations
Time frame: One year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Aug 2020.
- Individual participant dataSharing planned: Yes
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Radu Crisan-Dabija, MD, PhD contact
Adrian Covic, Professor study chair
Gr T Popa University of Medicine and Pharmacy Iasi ROMANIA
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Covid19 and Corona Virus Infection, run by Grigore T. Popa University of Medicine and Pharmacy at 1 site in Romania.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 19 Aug 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Romania. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alexandru Burlacu, MD, PhD (00407444488580, alexandru.burlacu@umfiasi.ro), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of patients with thrombophilic profile alterations (time frame: One year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Aug 2020.