Liver CirrhosisNCT03580577
Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic
An observational study of Liver Cirrhosis and Venous Thromboembolism, run by Assiut University at 1 site in Egypt.
Trial summary
patient with liver cirrhosis was supposed to have autoanticoagulation which approved to be wrong, with absence of conventional method to detect all abnormalities in coagulation state. Thromboelastography (TEG) give a broad picture for the coagulation defects. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Liver Cirrhosis, Venous Thromboembolism
- What is being tested?
- thromboelastography
- Type of treatment
- Medical device
- How many people
- 60 participants
- Where
- 1 siteEgypt
- Study dates
- 1 Sep 2018to 1 Sep 2019
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: liver cirrhosis patients with acute venous thromboembolism (VTE), control group of cirrhotic patients without VTE
Who may be able to join
- all cirrhotic patient who developed venous thromboembolic events
- written informed consent (patient or nearest relative )
Who cannot join
- Patient with chronic thromboembolic event ( e.g. chronic pulmonary embolism, chronic portal vein thrombosis).
- patients on antiplatelets or anticoagulants.
- Patients with end stage kidney, heart or lung diseases
- Pregnant.
- Cirrhotic patients on control group who develop an acute thromboembolic event during the study period will be excluded and shifted to the case group
Trial locations and contacts
1 site in 1 country.
Mohamed Abdel Sabour Mohamed Mekky contact
About this study
Official title: Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic Patients: A Hospital Based Prospective Study
patient with liver cirrhosis was supposed to have autoanticoagulation which approved to be wrong, with absence of conventional method to detect all abnormalities in coagulation state. Thromboelastography (TEG) give a broad picture for the coagulation defects.
In addition to that no guidelines prescribed anticoagulants for venous thromboembolism in cirrhotic, so the investigators will do a study to demonstrate frequency and risk factors for acute venous thromboembolism in cirrhotic patients, find a conventional laboratory method and test TEG to assess risk of thrombosis in cirrhotic patients.Also, to validate current algorithm for use of anticoagulant and antiplatelet for thromboembolism for non cirrhotic in cirrhotic patients.
Read the detailed description
Nowadays, the term "autoanticoagulated" ,which prescribed coagulopathy state in chronic liver disease (CLD) patients due to impaired synthesis of coagulation factors and elevated international normalized ratio(INR), has been approved to be wrong and those patients are liable for venous thromboembolism (VTE) with 0.5% - 6.3% incidence of deep venous thrombosis (DVT) and pulmonary thromboembolism (PE) among cirrhotic patients.
This may be explained by normal or even increased production of factor VIII and von Willebrand factor, enhanced thrombin activity and Low level of protein C, protein S and antithrombin III due to impaired liver synthesis, other risk factor include sedentary lifestyle, fractures, immobility, hospitalization, elevated estrogen levels, surgery, concomitant disease states and cancer, damaged vasculature that increases inflammation, and sluggish splanchnic blood flow, which are all common in those patients.
Absence of gold standard estimation for hypercoagulability in cirrhotic patients, is a big problem. During measurement of conventional parameters such as international normalized ratio (INR) or partial thromboplastin time, reagents used to measure the prothrombin time do not contain thrombomodulin on which protein C depend for activation, so it does not adequately reflect reduced levels protein C. Thromboelastography a device that has the ability to measure whole blood coagulation cascade including platelet function, It can be used to monitor coagulation status before liver transplantation operation to properly identify and treat coagulation abnormalities.
No worldwide guidelines is established neither for management nor prophylaxis of VTE in cirrhotic patients, this may be due to safety concerns regarding the risk of bleeding related to anticoagulant drugs when used in people with advanced liver disease, especially if there is significant thrombocytopenia, and/or the presence of varices.
- Conditions
- Liver Cirrhosis, Venous Thromboembolism
- Being tested
- thromboelastography
- Medical subject headings
- Liver Cirrhosis, Venous Thromboembolism
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
thromboelastographyDevice
thromboelastography will assess all coagulation abnormalities including platelets function in cirrhotic group with venous thromboembolism , and guide us about is there increased thrombosis risk or not, for that a fresh blood sample will be withdrawn from each patient before starting any treatment
| Study group | Role | What they receive |
|---|---|---|
| Cirrhotic with venous thromboembolism | cirrhotic patients with a venous thromboembolic event (including deep venous thrombosis, pulmonary embolism, acute non-malignant portal vein thrombosis, splenic vein, inferior vena cava thrombosis or mesenteric vascular occlusion).
Each patient will subjected to through history taking and careful examination to detect and risk factors also laboratory work to detect thrombocytopenia, disease severity, coagulation status thrombelastography before starting anticoagulants.
* Patients will start treatment with anticoagulants therapy after liaise with the specialized physician.
* Protein C, protein S and antithrombin III level will be assessed 3 months after the acute thrombotic event and 1 month of vitamin K antagonist (VKA) withdrawal. Receives: Device: thromboelastography | |
| Cirrhotic without venous thromboembolism | cirrhotic patients without any thrombotic events Each patient will subjected to through history taking and careful examination to detect and risk factors. - Protein C, protein S and antithrombin III level will be assessed at baseline. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Occurence of recanalization of thrombosed vessel
Efficacy of anticoagulants describe its ability to prevent further thrombosis and restore patency of thrmobosed vessel
Measured: 24 weeks from baseline
Secondary outcomes (2)
detect safety of anticoagulants in cirrhotic
Occurrence of any bleeding event while on anticoagulants therapy
Measured: During treatment period wither 12 or 24 weeks from starting therapy
Correlate thromboelastography results with hypercoagluable state in cirrhotic patients with venous thromboembolism
Changes in r, k and MA- TEG parameters in cirrhotic patients with venous thromboembolism
Measured: 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jul 2018
- Study start1 Sep 2018 (estimated)
- Primary completion30 Jun 2019 (estimated)
- Study completion1 Sep 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (12)Papers the sponsor has linked to this study.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- More trials run by Assiut UniversityThe sponsor's other registered studies.
- 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
- Case-control
- Time perspective
- Prospective
- Enrolment
- 60 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assiut University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ahmed Radwan Riad, Assiut University
- Investigators
- Mohamed Abdel Sabour Mohamed Mekky, Study director, Assiut University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03580577
- Sponsor's protocol ID
- Liver cirrhosis and thrombosis
- Status last verified
- Jul 2018
- First submitted
- 16 Jun 2018
- Last updated
- 30 Jul 2018
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008 Nov;53(11):3012-7. doi: 10.1007/s10620-008-0265-3. Epub 2008 Apr 29.
PubMed 18443906Northup PG, McMahon MM, Ruhl AP, Altschuler SE, Volk-Bednarz A, Caldwell SH, Berg CL. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006 Jul;101(7):1524-8; quiz 1680. doi: 10.1111/j.1572-0241.2006.00588.x.
PubMed 16863556Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017 Jun;66(6):1313-1326. doi: 10.1016/j.jhep.2017.01.006. Epub 2017 Jan 12.
PubMed 28088580Tripodi A, Primignani M, Chantarangkul V, Dell'Era A, Clerici M, de Franchis R, Colombo M, Mannucci PM. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-11. doi: 10.1053/j.gastro.2009.08.045. Epub 2009 Aug 23.
PubMed 19706293Tripodi A, Primignani M, Lemma L, Chantarangkul V, Mannucci PM. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol. 2013 Aug;59(2):265-70. doi: 10.1016/j.jhep.2013.03.036. Epub 2013 Apr 11.
PubMed 23583273Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell'Era A, Fabris F, Salerno F, Mannucci PM. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006 Aug;44(2):440-5. doi: 10.1002/hep.21266.
PubMed 16871542Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, Mannuccio Mannucci P. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005 Mar;41(3):553-8. doi: 10.1002/hep.20569.
PubMed 15726661van Wijngaarden A, van den Besselaar AM, Bertina RM. Thrombomodulin activity in commercial thromboplastin preparations. Thromb Res. 1986 Aug 1;43(3):265-74. doi: 10.1016/0049-3848(86)90146-5.
PubMed 3016943Tripodi A, Primignani M, Braham S, Chantarangkul V, Clerici M, Moia M, Peyvandi F. Coagulation parameters in patients with cirrhosis and portal vein thrombosis treated sequentially with low molecular weight heparin and vitamin K antagonists. Dig Liver Dis. 2016 Oct;48(10):1208-13. doi: 10.1016/j.dld.2016.06.027. Epub 2016 Jul 1.
PubMed 27470055HARTERT H. [Thrombelastography, a method for physical analysis of blood coagulation]. Z Gesamte Exp Med. 1951;117(2):189-203. No abstract available. Undetermined Language.
PubMed 14836887Collins S, MacIntyre C, Hewer I. Thromboelastography: Clinical Application, Interpretation, and Transfusion Management. AANA J. 2016 Apr;84(2):129-34.
PubMed 27311154MacIvor D, Rebel A, Hassan ZU. How do we integrate thromboelastography with perioperative transfusion management? Transfusion. 2013 Jul;53(7):1386-92. doi: 10.1111/j.1537-2995.2012.03728.x. Epub 2012 Jun 7. No abstract available.
PubMed 22670837
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Risk Factors and Outcomes of Acute Venous Thromboembolism in Cirrhotic Patients: A Hospital Based Prospective Study
- ClinicalTrials.gov ID
- NCT03580577
- Acronym / sponsor ID
- Liver cirrhosis and thrombosis
- Conditions
- Liver Cirrhosis, Venous Thromboembolism
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Assiut UniversityUniversity, hospital or other
- Study start
- 1 Sep 2018 (estimated)
- Primary completion
- 30 Jun 2019 (estimated)
- Study completion
- 1 Sep 2019 (estimated)
- First posted
- 9 Jul 2018 (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.
patient with liver cirrhosis was supposed to have autoanticoagulation which approved to be wrong, with absence of conventional method to detect all abnormalities in coagulation state. Thromboelastography (TEG) give a broad picture for the coagulation defects.
In addition to that no guidelines prescribed anticoagulants for venous thromboembolism in cirrhotic, so the investigators will do a study to demonstrate frequency and risk factors for acute venous thromboembolism in cirrhotic patients, find a conventional laboratory method and test TEG to assess risk of thrombosis in cirrhotic patients.Also, to validate current algorithm for use of anticoagulant and antiplatelet for thromboembolism for non cirrhotic in cirrhotic patients.
Detailed description
Nowadays, the term "autoanticoagulated" ,which prescribed coagulopathy state in chronic liver disease (CLD) patients due to impaired synthesis of coagulation factors and elevated international normalized ratio(INR), has been approved to be wrong and those patients are liable for venous thromboembolism (VTE) with 0.5% - 6.3% incidence of deep venous thrombosis (DVT) and pulmonary thromboembolism (PE) among cirrhotic patients.
This may be explained by normal or even increased production of factor VIII and von Willebrand factor, enhanced thrombin activity and Low level of protein C, protein S and antithrombin III due to impaired liver synthesis, other risk factor include sedentary lifestyle, fractures, immobility, hospitalization, elevated estrogen levels, surgery, concomitant disease states and cancer, damaged vasculature that increases inflammation, and sluggish splanchnic blood flow, which are all common in those patients.
Absence of gold standard estimation for hypercoagulability in cirrhotic patients, is a big problem. During measurement of conventional parameters such as international normalized ratio (INR) or partial thromboplastin time, reagents used to measure the prothrombin time do not contain thrombomodulin on which protein C depend for activation, so it does not adequately reflect reduced levels protein C. Thromboelastography a device that has the ability to measure whole blood coagulation cascade including platelet function, It can be used to monitor coagulation status before liver transplantation operation to properly identify and treat coagulation abnormalities.
No worldwide guidelines is established neither for management nor prophylaxis of VTE in cirrhotic patients, this may be due to safety concerns regarding the risk of bleeding related to anticoagulant drugs when used in people with advanced liver disease, especially if there is significant thrombocytopenia, and/or the presence of varices.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cirrhotic with venous thromboembolism | – | Device: thromboelastographycirrhotic patients with a venous thromboembolic event (including deep venous thrombosis, pulmonary embolism, acute non-malignant portal vein thrombosis, splenic vein, inferior vena cava thrombosis or mesenteric vascular occlusion). Each patient will subjected to through history taking and careful examination to detect and risk factors also laboratory work to detect thrombocytopenia, disease severity, coagulation status thrombelastography before starting anticoagulants. * Patients will start treatment with anticoagulants therapy after liaise with the specialized physician. * Protein C, protein S and antithrombin III level will be assessed 3 months after the acute thrombotic event and 1 month of vitamin K antagonist (VKA) withdrawal. |
| Cirrhotic without venous thromboembolism | – | –cirrhotic patients without any thrombotic events Each patient will subjected to through history taking and careful examination to detect and risk factors. - Protein C, protein S and antithrombin III level will be assessed at baseline. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- liver cirrhosis patients with acute venous thromboembolism (VTE), control group of cirrhotic patients without VTE
Key inclusion criteria (2 listed)
- all cirrhotic patient who developed venous thromboembolic events
- written informed consent (patient or nearest relative )
Key exclusion criteria (5 listed)
- Patient with chronic thromboembolic event ( e.g. chronic pulmonary embolism, chronic portal vein thrombosis).
- patients on antiplatelets or anticoagulants.
- Patients with end stage kidney, heart or lung diseases
- Pregnant.
- Cirrhotic patients on control group who develop an acute thromboembolic event during the study period will be excluded and shifted to the case group
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 |
|---|---|---|
| thromboelastographythromboelastography will assess all coagulation abnormalities including platelets function in cirrhotic group with venous thromboembolism , and guide us about is there increased thrombosis risk or not, for that a fresh blood sample will be withdrawn from each patient before starting any treatment | Device | Cirrhotic with venous thromboembolism |
Primary outcome
Occurence of recanalization of thrombosed vessel
Time frame: 24 weeks from baseline
Efficacy of anticoagulants describe its ability to prevent further thrombosis and restore patency of thrmobosed vessel
2 secondary outcomes
detect safety of anticoagulants in cirrhotic
Time frame: During treatment period wither 12 or 24 weeks from starting therapy
Correlate thromboelastography results with hypercoagluable state in cirrhotic patients with venous thromboembolism
Time frame: 1 day
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2018.
- Background: PubMed 18443906Gulley D, Teal E, Suvannasankha A, Chalasani N, Liangpunsakul S. Deep vein thrombosis and pulmonary embolism in cirrhosis patients. Dig Dis Sci. 2008 Nov;53(11):3012-7. doi: 10.1007/s10620-008-0265-3. Epub 2008 Apr 29.
- Background: PubMed 16863556Northup PG, McMahon MM, Ruhl AP, Altschuler SE, Volk-Bednarz A, Caldwell SH, Berg CL. Coagulopathy does not fully protect hospitalized cirrhosis patients from peripheral venous thromboembolism. Am J Gastroenterol. 2006 Jul;101(7):1524-8; quiz 1680. doi: 10.1111/j.1572-0241.2006.00588.x.
- Background: PubMed 28088580Dhar A, Mullish BH, Thursz MR. Anticoagulation in chronic liver disease. J Hepatol. 2017 Jun;66(6):1313-1326. doi: 10.1016/j.jhep.2017.01.006. Epub 2017 Jan 12.
- Background: PubMed 19706293Tripodi A, Primignani M, Chantarangkul V, Dell'Era A, Clerici M, de Franchis R, Colombo M, Mannucci PM. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology. 2009 Dec;137(6):2105-11. doi: 10.1053/j.gastro.2009.08.045. Epub 2009 Aug 23.
- Background: PubMed 23583273Tripodi A, Primignani M, Lemma L, Chantarangkul V, Mannucci PM. Evidence that low protein C contributes to the procoagulant imbalance in cirrhosis. J Hepatol. 2013 Aug;59(2):265-70. doi: 10.1016/j.jhep.2013.03.036. Epub 2013 Apr 11.
- Background: PubMed 16871542Tripodi A, Primignani M, Chantarangkul V, Clerici M, Dell'Era A, Fabris F, Salerno F, Mannucci PM. Thrombin generation in patients with cirrhosis: the role of platelets. Hepatology. 2006 Aug;44(2):440-5. doi: 10.1002/hep.21266.
- Background: PubMed 15726661Tripodi A, Salerno F, Chantarangkul V, Clerici M, Cazzaniga M, Primignani M, Mannuccio Mannucci P. Evidence of normal thrombin generation in cirrhosis despite abnormal conventional coagulation tests. Hepatology. 2005 Mar;41(3):553-8. doi: 10.1002/hep.20569.
- Background: PubMed 3016943van Wijngaarden A, van den Besselaar AM, Bertina RM. Thrombomodulin activity in commercial thromboplastin preparations. Thromb Res. 1986 Aug 1;43(3):265-74. doi: 10.1016/0049-3848(86)90146-5.
- Background: PubMed 27470055Tripodi A, Primignani M, Braham S, Chantarangkul V, Clerici M, Moia M, Peyvandi F. Coagulation parameters in patients with cirrhosis and portal vein thrombosis treated sequentially with low molecular weight heparin and vitamin K antagonists. Dig Liver Dis. 2016 Oct;48(10):1208-13. doi: 10.1016/j.dld.2016.06.027. Epub 2016 Jul 1.
- Background: PubMed 14836887HARTERT H. [Thrombelastography, a method for physical analysis of blood coagulation]. Z Gesamte Exp Med. 1951;117(2):189-203. No abstract available. Undetermined Language.
- Background: PubMed 27311154Collins S, MacIntyre C, Hewer I. Thromboelastography: Clinical Application, Interpretation, and Transfusion Management. AANA J. 2016 Apr;84(2):129-34.
- Background: PubMed 22670837MacIvor D, Rebel A, Hassan ZU. How do we integrate thromboelastography with perioperative transfusion management? Transfusion. 2013 Jul;53(7):1386-92. doi: 10.1111/j.1537-2995.2012.03728.x. Epub 2012 Jun 7. No abstract available.
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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.
Mohamed Abdel Sabour Mohamed Mekky contact
Mohamed Abdel Sabour Mohamed Mekky study director
Assiut University
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 Liver Cirrhosis and Venous Thromboembolism, run by Assiut University at 1 site in Egypt.
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 2 inclusion and 5 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 30 Jul 2018. 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 Egypt. 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 Ahmed Radwan Riad (+2 01126435001, dr.radwan1988@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Occurence of recanalization of thrombosed vessel (time frame: 24 weeks from baseline). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03580577, which also lists 12 linked publications.
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 30 Jul 2018.