Hepatic Vein ThrombosesLiv-ThrombusNCT05123326
Global Coagulation Assessment in Portal Vein Thrombosis and Budd-Chiari Syndrome
An observational study of Hepatic Vein Thromboses and Hepatic Venous Outflow Obstruction, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
Trial summary
Portal vein thrombosis is defined as partial or complete occlusion of the portal vein lumen by the blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, known as 'portal cavernoma'. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Hepatic Vein Thromboses, Hepatic Venous Outflow Obstruction, Portal Vein Thrombosis
- What is being tested?
- Rotational thromboelastometry, Genetic tests for Thrombophilia and ELISA tests/ Functional assays
- How many people
- 300 participants
- Where
- 1 siteIndia
- Study dates
- 15 Oct 2021to 15 Oct 2024
- 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 to 65 years
- All sexes
- Adult, Older adult
Study population: All patients with PVT and HVOTO fitting the inclusion criteria will be prospectively enrolled in the study
Who may be able to join
- Gender: Either gender
- Age:18 - 65 years of age
- Patient with portal vein thrombosis documented on imaging (USG with color doppler, CECT abdomen and CEMRI abdomen
Who cannot join
- Patients who do not consent to the study.
- Patient with pregnancy and lactation
- Patients with a history of blood transfusions in the last two weeks
- Patients who are too sick to undergo screening tests.
- Patients on hemodialysis
- Chronic heart failure and chronic pulmonary or end-stage renal disease
- Patients who are on plasma therapy
Trial locations and contacts
1 site in 1 country.
India1 site, 1 recruiting
- Recruiting
Postgraduate Institute of Medical Education and Research
Chandigarh, Choose Any State/Province, 160012
Madhumita Premkumar, MD DM, drmadhumitap@gmail.com
Harmanpreet Kaur, MSc, 0172-2754777
About this study
Official title: Prospective Evaluation of Coagulation Status and Thromboelastometry Guided Management of Genetic and Acquired Thrombophilia in Patients With Portal Vein Thrombosis and Budd-Chiari Syndrome
Portal vein thrombosis is defined as partial or complete occlusion of the portal vein lumen by the blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, known as 'portal cavernoma'. [1,2] Based on the published literature, 15-25% of patients with cirrhosis have portal vein thrombosis (PVT) [3], and 35-50% of patients with hepatocellular carcinoma (HCC) have malignant PVT [4] compared to 1-3.8 per 100,000 patients in the general population. [5] The reported cumulative incidence of PVT in patients of Child-Pugh A and B is 4.6% and 10.7% at 1 and 5 years respectively with higher incidence among those with decompensated disease or with an underlying hypercoagulable disorder. [6]. Similarly, the prevalence of PVT in compensated cirrhosis is around 1% which increases to 8 - 25% in liver transplant (LT) candidates and 40% in patients with hepatocellular carcinoma (HCC) [7,8]. Based on the published literature 7-9 % of all chronic liver disease patients have hepatic vein outflow tract obstruction (HVOTO) in the Indian population. [9] HVOTO is defined as obstruction to hepatic venous outflow at any site from the right atrium inlet to the small hepatic venules. The Budd-Chiari syndrome (BCS) results from occlusion of one or more hepatic veins (HV) and/or the inferior vena cava (IVC). In the West, the most common cause is HV occlusion by thrombosis. More recent Indian studies have however shown that isolated HV and combined IVC+HV obstruction are now more common. [10]
In the post COVID-19 era, there has been great interest in the prothrombotic states associated with the SARS-Cov-2 virus infection, and the adverse effects of some vaccines. [11] With the availability of better molecular tests for hypercoagulable states, use of global coagulation tests (GCT) like rotational thromboelastometry (ROTEM), thromboelastography (TEG) and Sonoclot, use of therapeutic procedures like Transjugular intrahepatic portosystemic shunt (TIPS), availability of novel oral anticoagulants (NOAC), the natural course of disease can be changed with good outcomes. [12] Standard Coagulation tests (SCTs) like PT, aPTT, and platelet count are not predictive of bleeding or coagulation risk as they exclude the cellular elements of hemostasis and are unable to assess the effect of thrombomodulin and cannot assess the stage of the coagulation pathway which is affected. Global coagulation tests provide dynamic information on the coagulation pathway that is not available from conventional tests. [13]
Read the detailed description
Our proposed study is important for the following 4 reasons.
- SCTs cannot be used to demonstrate the thrombomodulin mediated normal thrombin generation in patients with liver disease, so the monitoring of such patient using global coagulation tests can be validated. The use of point-of-care global coagulation tests like ROTEM and Sonoclot enables us to identify the true prothrombotic and hypocoagulable states which can be used to assess for increased clot strength, clot formation time, and indicate hyperfibrinolysis. The use of conventional tests like prothrombin time, partial thromboplastin time and INR cannot bolster the therapeutic strategy.
- This study will also help to determine role of global coagulation tests rather than PT/INR /aPTT in monitoring the dose and response of anticoagulants like vitamin K antagonists and novel oral anticoagulants (NOAC) in patients who are on therapeutic anticoagulation for HVOTO/PVT.
- This study will also help to determine the prevalence and role of CALR, JAK2V617F, factor V Leiden mutations in patients with PVT and HVOTO in our population.
- We will also be prospectively assessing the rate of thrombophilia complications in the Post COVID-19 era, and the study will generate information regarding new incidence of PVT/HVOTO in those exposed to COVID-19.
Therefore, the current study is the need of the hour, as we intend to assess the relevance of PVT and outcomes, test the genetic predisposition of Indian patients to hyper coagulable states, develop anticoagulation algorithms using NOAC, and determine the true burden on disease in India.
- Conditions
- Hepatic Vein Thromboses, Hepatic Venous Outflow Obstruction, Portal Vein Thrombosis, Portal Hypertension, Noncirrhotic, Portal Vein Occlusion, Portal Vein Embolism
- Being tested
- Rotational thromboelastometry, Genetic tests for Thrombophilia, ELISA tests/ Functional assays
- Medical subject headings
- Budd-Chiari Syndrome, Hypertension, Portal, Hemostatic Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Rotational thromboelastometryDiagnostic test
Also called Global coagulation test
ROTEM/ Sonoclot tests will be done in all patients at enrolment and after initiating anticoagulation in those who are eligible for the same.
Genetic tests for ThrombophiliaDiagnostic test
Tests for JAK2 mutation, CAL R mutation and Factor V Leiden mutation will be done.
ELISA tests/ Functional assaysDiagnostic test
Antithrombin III, Protein C, Protein S, Factor VIII, VWF using commercial assays
| Study group | Role | What they receive |
|---|---|---|
| PVT | Portal Vein Thrombosis (PVT) refers to partial or complete occlusion of the portal vein lumen by a blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, commonly known as 'portal cavernoma.' 240 patients to be recruited Receives: Diagnostic Test: Rotational thromboelastometry; Diagnostic Test: Genetic tests for Thrombophilia; Diagnostic Test: ELISA tests/ Functional assays | |
| HVOTO | Occlusion of two or more hepatic veins. 100 patients Receives: Diagnostic Test: Rotational thromboelastometry; Diagnostic Test: Genetic tests for Thrombophilia; Diagnostic Test: ELISA tests/ Functional assays |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical presentation
Number of participants with clinical and imaging evidence of PVT and HVOTO in our patient population
Measured: At enrolment
Clinical presentation- Extent of disease
Grading of PVT and HVOTO in our patient population
Measured: At enrolment
Occurrence of new thrombotic complications
Description of new sites of thrombosis spectrum of PVT and HVOTO in our patient population
Measured: At enrolment-3 years
Occurrence of all thrombotic complications after anticoagulation
Description of new sites of thrombosis spectrum of PVT and HVOTO after anticoagulation
Measured: At enrolment-3 years
Comparison of performance of standard coagulation tests vs. global coagulation tests to determine the hypercoagulable defect
PT aPTT INR
Measured: At enrolment
Comparison of performance of global coagulation tests to determine the hypercoagulable defect
ROTEM/Sonoclot
Measured: At enrolment
Secondary outcomes (6)
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
JAK2, CALR, Factor V Leiden mutation
Measured: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
CALR mutation test
Measured: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
Factor V Leiden mutation
Measured: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
JAK2 mutation test
Measured: At enrolment
Occurrence of new hemorrhagic complications
Sites of bleeding in patients who are not on anticoagulation
Measured: At enrolment-3 years
Occurrence of new hemorrhagic complications in anticoagulated patients
Sites of bleeding in patients who are on anticoagulation
Measured: At enrolment-3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Nov 2021
- Study start15 Oct 2021
- Primary completion15 Oct 2024 (estimated)
- Study completion15 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic Vein ThrombosesStudies 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
- Cohort
- Time perspective
- Prospective
- Enrolment
- 300 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Madhumita Premkumar, Post Graduate Institute of Medical Education and Research, Chandigarh
- Investigators
- Madhumita Premkumar, MD DM, Principal investigator, Post Graduate Institute of Medical Education and Research, Chandigarh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05123326
- Sponsor's protocol ID
- PGI/IEC/2021/001451
- Acronym
- Liv-Thrombus
- Status last verified
- Feb 2024
- First submitted
- 3 Nov 2021
- Last updated
- 13 Feb 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prospective Evaluation of Coagulation Status and Thromboelastometry Guided Management of Genetic and Acquired Thrombophilia in Patients With Portal Vein Thrombosis and Budd-Chiari Syndrome
- ClinicalTrials.gov ID
- NCT05123326
- Acronym / sponsor ID
- Liv-Thrombus / PGI/IEC/2021/001451
- Conditions
- Hepatic Vein Thromboses, Hepatic Venous Outflow Obstruction, Portal Vein Thrombosis, Portal Hypertension, Noncirrhotic, Portal Vein Occlusion, Portal Vein Embolism
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 300 participants (estimated)
- Lead sponsor
- Post Graduate Institute of Medical Education and Research, ChandigarhUniversity, hospital or other
- Study start
- 15 Oct 2021 (actual)
- Primary completion
- 15 Oct 2024 (estimated)
- Study completion
- 15 Oct 2024 (estimated)
- First posted
- 17 Nov 2021 (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.
Portal vein thrombosis is defined as partial or complete occlusion of the portal vein lumen by the blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, known as 'portal cavernoma'. [1,2] Based on the published literature, 15-25% of patients with cirrhosis have portal vein thrombosis (PVT) [3], and 35-50% of patients with hepatocellular carcinoma (HCC) have malignant PVT [4] compared to 1-3.8 per 100,000 patients in the general population. [5] The reported cumulative incidence of PVT in patients of Child-Pugh A and B is 4.6% and 10.7% at 1 and 5 years respectively with higher incidence among those with decompensated disease or with an underlying hypercoagulable disorder. [6]. Similarly, the prevalence of PVT in compensated cirrhosis is around 1% which increases to 8 - 25% in liver transplant (LT) candidates and 40% in patients with hepatocellular carcinoma (HCC) [7,8]. Based on the published literature 7-9 % of all chronic liver disease patients have hepatic vein outflow tract obstruction (HVOTO) in the Indian population. [9] HVOTO is defined as obstruction to hepatic venous outflow at any site from the right atrium inlet to the small hepatic venules. The Budd-Chiari syndrome (BCS) results from occlusion of one or more hepatic veins (HV) and/or the inferior vena cava (IVC). In the West, the most common cause is HV occlusion by thrombosis. More recent Indian studies have however shown that isolated HV and combined IVC+HV obstruction are now more common. [10]
In the post COVID-19 era, there has been great interest in the prothrombotic states associated with the SARS-Cov-2 virus infection, and the adverse effects of some vaccines. [11] With the availability of better molecular tests for hypercoagulable states, use of global coagulation tests (GCT) like rotational thromboelastometry (ROTEM), thromboelastography (TEG) and Sonoclot, use of therapeutic procedures like Transjugular intrahepatic portosystemic shunt (TIPS), availability of novel oral anticoagulants (NOAC), the natural course of disease can be changed with good outcomes. [12] Standard Coagulation tests (SCTs) like PT, aPTT, and platelet count are not predictive of bleeding or coagulation risk as they exclude the cellular elements of hemostasis and are unable to assess the effect of thrombomodulin and cannot assess the stage of the coagulation pathway which is affected. Global coagulation tests provide dynamic information on the coagulation pathway that is not available from conventional tests. [13]
Detailed description
Our proposed study is important for the following 4 reasons.
- SCTs cannot be used to demonstrate the thrombomodulin mediated normal thrombin generation in patients with liver disease, so the monitoring of such patient using global coagulation tests can be validated. The use of point-of-care global coagulation tests like ROTEM and Sonoclot enables us to identify the true prothrombotic and hypocoagulable states which can be used to assess for increased clot strength, clot formation time, and indicate hyperfibrinolysis. The use of conventional tests like prothrombin time, partial thromboplastin time and INR cannot bolster the therapeutic strategy.
- This study will also help to determine role of global coagulation tests rather than PT/INR /aPTT in monitoring the dose and response of anticoagulants like vitamin K antagonists and novel oral anticoagulants (NOAC) in patients who are on therapeutic anticoagulation for HVOTO/PVT.
- This study will also help to determine the prevalence and role of CALR, JAK2V617F, factor V Leiden mutations in patients with PVT and HVOTO in our population.
- We will also be prospectively assessing the rate of thrombophilia complications in the Post COVID-19 era, and the study will generate information regarding new incidence of PVT/HVOTO in those exposed to COVID-19.
Therefore, the current study is the need of the hour, as we intend to assess the relevance of PVT and outcomes, test the genetic predisposition of Indian patients to hyper coagulable states, develop anticoagulation algorithms using NOAC, and determine the true burden on disease in India.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PVT | – | Diagnostic Test: Rotational thromboelastometry, Diagnostic Test: Genetic tests for Thrombophilia, Diagnostic Test: ELISA tests/ Functional assaysPortal Vein Thrombosis (PVT) refers to partial or complete occlusion of the portal vein lumen by a blood clot or its replacement by multiple collateral vessels with the hepato-petal flow, commonly known as 'portal cavernoma.' 240 patients to be recruited |
| HVOTO | – | Diagnostic Test: Rotational thromboelastometry, Diagnostic Test: Genetic tests for Thrombophilia, Diagnostic Test: ELISA tests/ Functional assaysOcclusion of two or more hepatic veins. 100 patients |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- All patients with PVT and HVOTO fitting the inclusion criteria will be prospectively enrolled in the study
Key inclusion criteria (3 listed)
- Gender: Either gender
- Age:18 - 65 years of age
- Patient with portal vein thrombosis documented on imaging (USG with color doppler, CECT abdomen and CEMRI abdomen
Key exclusion criteria (7 listed)
- Patients who do not consent to the study.
- Patient with pregnancy and lactation
- Patients with a history of blood transfusions in the last two weeks
- Patients who are too sick to undergo screening tests.
- Patients on hemodialysis
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 |
|---|---|---|
| Rotational thromboelastometryAlso: Global coagulation testROTEM/ Sonoclot tests will be done in all patients at enrolment and after initiating anticoagulation in those who are eligible for the same. | Diagnostic test | HVOTO, PVT |
| Genetic tests for ThrombophiliaTests for JAK2 mutation, CAL R mutation and Factor V Leiden mutation will be done. | Diagnostic test | HVOTO, PVT |
| ELISA tests/ Functional assaysAntithrombin III, Protein C, Protein S, Factor VIII, VWF using commercial assays | Diagnostic test | HVOTO, PVT |
Primary outcome
Clinical presentation
Time frame: At enrolment
Number of participants with clinical and imaging evidence of PVT and HVOTO in our patient population
Clinical presentation- Extent of disease
Time frame: At enrolment
Grading of PVT and HVOTO in our patient population
Occurrence of new thrombotic complications
Time frame: At enrolment-3 years
Description of new sites of thrombosis spectrum of PVT and HVOTO in our patient population
Occurrence of all thrombotic complications after anticoagulation
Time frame: At enrolment-3 years
Description of new sites of thrombosis spectrum of PVT and HVOTO after anticoagulation
Comparison of performance of standard coagulation tests vs. global coagulation tests to determine the hypercoagulable defect
Time frame: At enrolment
PT aPTT INR
Comparison of performance of global coagulation tests to determine the hypercoagulable defect
Time frame: At enrolment
ROTEM/Sonoclot
6 secondary outcomes
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
Time frame: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
Time frame: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
Time frame: At enrolment
Assessment of genetic predisposition of hypercoagulable states in PVT and HVOTO
Time frame: At enrolment
Occurrence of new hemorrhagic complications
Time frame: At enrolment-3 years
Occurrence of new hemorrhagic complications in anticoagulated patients
Time frame: At enrolment-3 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Feb 2024.
- Individual participant dataSharing planned: Undecided
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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.
Madhumita Premkumar, MD DM principal investigator
Post Graduate Institute of Medical Education and Research, Chandigarh
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 Hepatic Vein Thromboses and Hepatic Venous Outflow Obstruction, run by Post Graduate Institute of Medical Education and Research, Chandigarh at 1 site in India.
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 3 inclusion and 7 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 13 Feb 2024. 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 India. 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 Madhumita Prem Kumar, MD DM (0172-2754777, drmadhumitap@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical presentation (time frame: At enrolment). The study lists 6 primary outcomes in all. 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 13 Feb 2024.