Snake BitesHISSNCT04520282
Hemostatic Variables In Snakebite Study
An observational study of Snake Bites and Coagulopathy, Consumption, run by Jubilee Mission Medical College and Research Institute at 1 site in India.
Trial summary
Background Novelty The global assays of coagulation, namely the viscoelastometric tests and clot waveform has never been studied in detail before in snakebite victims. The pathophysiology of VICC including specific factor deficiencies and serial trend in blood cell indices amongst various hematotoxic snakebite in the… Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Snake Bites, Coagulopathy, Consumption
- How many people
- 96 participants
- Where
- 1 siteIndia
- Study dates
- 15 Mar 2022to 9 Aug 2023
- 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: All patients with history suggestive of snakebite presenting within 6 hours of snakebite and providing a written informed consent and/or assent would be included in the study Definitions: 'Snakebite' OR 'History suggestive of snakebite' would be defined as, patients or their bystander claiming in sound mind not and not under the influence of any inebriants, to have witnessed being bitten by a snake, OR, patient with clinical features of snakebite as suspected by the clinician on floor
Who may be able to join
- All patients with history suggestive of snakebite presenting within 6 hours of snakebite AND
- All providing a written informed consent and/or assent
Who cannot join
- All patients of stings or bites other than snakes
- All patients who received antivenom or blood products at another institute
- All patients with known hematological malignancies, coagulation disorders, chronic liver or renal failure.
- All patients known to be on warfarin, heparin or any newer oral or injectable anticoagulants
- All withdrawing a consent later on, or withdrawing assent later on-
Trial locations and contacts
1 site in 1 country.
India1 site
Jubilee Mission Medical College and Research Institute
Thrissur, Kerala, 680005
About this study
Official title: Haemostatic Variables in Snakebite: a Regional Prospective Cohort to Identify the Role of Global Coagulation Assays and Serial Laboratory Testing in the Management of Snakebite Coagulopathy
Background
Novelty The global assays of coagulation, namely the viscoelastometric tests and clot waveform has never been studied in detail before in snakebite victims.
The pathophysiology of VICC including specific factor deficiencies and serial trend in blood cell indices amongst various hematotoxic snakebite in the region is not known.
No Indian study to date has systematically examined the changes in early laboratory tests results in envenomed and non envenomed snakebite victims.
Read the detailed description
The problem:
Snakebite is a neglected disease of the poor in India. Nearly 50,000 individuals die of snake bite every year in the country, making it the region with most number of snakebite related deaths in the world.
Snakebite though is one of the leading cause of mortality and morbidity globally, it is in fact a "local" problem which warrants a regionalized approach. The venom characteristics of snakes and their response to treatment vary across geographical regions, even within the same species.
Therefore the venom sourcing for antivenom production, to clinical characterization of snakebites needs to be regionalized.
Clinical profiling of snakebite has been done in many observational studies across the region but a comprehensive prospective regional profiling of laboratory parameters including the global assays have not been done to date.
The health care in India is mostly out of one's own pocket, and the victims are of the lower socio economic strata the health care costs are seldom affordable. Research in the field is also sparse due to lack of funding for the same. The investigators through this research aim to study the clinical and laboratory profile of snakebite victims presenting to a tertiary care snakebite treatment centre in central Kerala and the role of global coagulation assays in the management of the same.
Once answered, the research question, would provide a better understanding of the hematotoxic snakebite in the region.
It could aid in better patient care strategies, including possible determination of a better test for coagulopathy, judicious antivenom and blood product usage.
Its relevance in local, national and international context:.
Snakebite being region specific warrants a region specific approach to the problem. Venomous species like Humpnosed pit viper (Hypnale hypnale) envenomation which is the second most common snakebite (first being Daboia russelli ) in the region is a serious problem that needs better understanding.
This would be a model which can be replicated in selected tertiary care snakebite centers across the country. Answering these research questions across the country would lead to better understanding of coagulopathy in snakebite, its response to antivenom and blood products in India.
It may also lead to quantifying the need for region specific antivenom in the country.
No Indian study has systematically examined the changes in early laboratory tests results in envenomed and non envenomed snakebite victims to date.
With the exception of a few case reports there has been no studies that has looked at the performance of global coagulation assays in the country.
The country that becomes the largest contributor of global burden of snake bite in terms of mortality is India.
This model if applicable in India, should be replicable elsewhere too. Ten years back, the investigators would not have been able to envision this study, since the understanding of the process of snake bite related coagulopathy was limited, and it was national projects like the Australian snake bite project implemented elsewhere that form the basis for the current understanding of the problem of snakebite.
In the international context many other low and middle income countries that are burdened by snake bites would benefit from any result in terms of a better bedside coagulation test (like CWA or MLW) or a cheaper blood indices (DNI) to prognosticate snake envenomation.
The understanding of coagulopathy in snakebite is now changing. Conventionally, although this coagulopathy is likened to disseminated intravascular coagulation (DIC), in the recent years, it has been described as venom-induced consumptive coagulopathy (VICC).
VICC defers from DIC in its rapidity of both onset and resolution. It used to be compared to Disseminated Intravascular Coagulation, but now the understanding of the same is changing and more recently the term VICC- Venom induced consumptive coagulopathy has been introduced. The snake venom in India are known to contain Factor V activators (D russelli), Factor X activators (D russelli), prothrombin activators (PTA) (Echis sp.), thrombin like enzymes (TLE) and fibrinogenases (Trimeresurus sp,. Hypnale hypnale). The above mentioned findings are mostly from studies in Srilanka, with assays done in samples frozen and sent to Australia, by the same team of investigators.
There are not many properly conducted study from any region of India that helps understand the pathophysiology better.
- Conditions
- Snake Bites, Coagulopathy, Consumption
- Keywords
- global coagulation assay, hemostatic variables, coagulopathy, VICC, DIC, Venom induced consumptive coagulopathy, Disseminated intravascular coagulation, ROTEM, CWA, clot waveform analysis, 20'WBCT, Clotting time, thromboelastometry, viscoelastometry, blood cell indices, snakebite, hematotoxic
- Medical subject headings
- Snake Bites, Disseminated Intravascular Coagulation, Hemostatic Disorders
What is being measured
The primary outcome is the main question the study is designed to answer.
To study the serial change in CT of snakebite victims
Change from baseline (sample taken at admission) for clotting time would be recorded in minutes and seconds assessed at 1 hour (post admission), 1 hour 30 mins (post admission), 3 hours (post admission), 6 hours (post bite), 6 hours post antivenom, 6 hours after blood products or 12 hours after antivenom and at discharge or at 30 days (whichever is earlier)
Measured: up to 30 days
To study the serial change in fibrinogen levels of snakebite victims
The change in fibrinogen levels from baseline (sample taken at admission, 0 hour), 6 hour post bite, 6 hours post antivenom,12 hours post antivenom, 6 hours after blood products and at discharge or at 30 days (whichever occurs earlier), measured in weight per volume (milligram per decilitre).
Measured: up to 30 days
To study the serial change in D dimer levels of snakebite victims
The change D dimer from baseline (sample taken at admission, 0 hour), 6 hour post bite, 6 hours post antivenom,12 hours post antivenom, 6 hours after blood products and at discharge or at 30 days (whichever occurs earlier) measured in weight per volume ( micrograms per decilitre respectively).
Measured: up to 30 days
Secondary outcomes (6)
Diagnostic accuracy of Clotting Time in detecting coagulopathy
Sensitivity and specificity of Clotting Time (minutes) done using Modified Lee and White method (MLW) in detecting coagulopathy compared to conventional coagulation test (PT, aPTT)
Measured: 48 hours
Diagnostic accuracy of 20'WBCT, MLW, Delayed reading of 20'WBCT in detecting coagulopathy
Sensitivity, specificity of
- 20'WBCT (minutes)
- Delayed reading of 20'WBCT (30'WBCT) in detecting coagulopathy compared to conventional coagulation test (PT, aPTT)
Measured: 48 hours
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of the bedside coagulation tests.
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of bedside coagulation tests (20'WBCT, MLW Clotting time, Delayed reading of 20'WBCT, Activated Clotting Time) (before and after antivenom)
Measured: 48 hours
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation conventional coagulation tests
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of conventional coagulation tests PT/INR and aPTT (before and after antivenom)
Measured: 48 hours
To study the serial change in PT and aPTT-clot waveform of snakebite victims
The change of PT and aPTT-clot waveform from baseline (sample taken at admission; 0 Hours) would be recorded in milli absorption (mabs) per second, 6 hours (post bite), 6 hours post antivenom, 12 hours post antivenom ,6 hours after blood products and at discharge or 7 days whichever is earlier
Measured: up to 7 days
To describe the clinical characteristics of snakebite victims measured as per a pre set proforma
The clinical characteristics of snakebite victims, including systemic manifestation and local manifestations would be measured as per a pre set proforma
Measured: up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Aug 2020
- Study start15 Mar 2022
- Primary completion31 Jul 2023
- Study completion9 Aug 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Snake BitesStudies 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
- 96 participants (actual)
Sponsor and investigators
- Lead sponsor
- Jubilee Mission Medical College and Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Siju V Abraham, MD, Jubilee Mission Medical College and Research Institute
- Investigators
- Siju V Abraham, M D, Principal investigator, Jubilee Mission Medical College and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04520282
- Sponsor's protocol ID
- 01/20/IEC/JMMC&RI
- Other IDs
- U1111-1252-7998
- Acronym
- HISS
- Status last verified
- Mar 2024
- First submitted
- 31 May 2020
- Last updated
- 7 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Abraham SV, Rafi AM, Krishnan SV, Palatty BU, Innah SJ, Johny J, Varghese S. Utility of Clot Waveform Analysis in Russell's Viper Bite Victims with Hematotoxicity. J Emerg Trauma Shock. 2018 Jul-Sep;11(3):211-216. doi: 10.4103/JETS.JETS_43_17.
PubMed 30429630
Study at a glance
From the registry record, last updated by the sponsor on 7 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Haemostatic Variables in Snakebite: a Regional Prospective Cohort to Identify the Role of Global Coagulation Assays and Serial Laboratory Testing in the Management of Snakebite Coagulopathy
- ClinicalTrials.gov ID
- NCT04520282
- Acronym / sponsor ID
- HISS / 01/20/IEC/JMMC&RI
- Conditions
- Snake Bites, Coagulopathy, Consumption
- Keywords
- global coagulation assay, hemostatic variables, coagulopathy, VICC, DIC, Venom induced consumptive coagulopathy, Disseminated intravascular coagulation, ROTEM
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Jubilee Mission Medical College and Research InstituteUniversity, hospital or other
- Study start
- 15 Mar 2022 (actual)
- Primary completion
- 31 Jul 2023 (actual)
- Study completion
- 9 Aug 2023 (actual)
- First posted
- 20 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.
Background
Novelty The global assays of coagulation, namely the viscoelastometric tests and clot waveform has never been studied in detail before in snakebite victims.
The pathophysiology of VICC including specific factor deficiencies and serial trend in blood cell indices amongst various hematotoxic snakebite in the region is not known.
No Indian study to date has systematically examined the changes in early laboratory tests results in envenomed and non envenomed snakebite victims.
Detailed description
The problem:
Snakebite is a neglected disease of the poor in India. Nearly 50,000 individuals die of snake bite every year in the country, making it the region with most number of snakebite related deaths in the world.
Snakebite though is one of the leading cause of mortality and morbidity globally, it is in fact a "local" problem which warrants a regionalized approach. The venom characteristics of snakes and their response to treatment vary across geographical regions, even within the same species.
Therefore the venom sourcing for antivenom production, to clinical characterization of snakebites needs to be regionalized.
Clinical profiling of snakebite has been done in many observational studies across the region but a comprehensive prospective regional profiling of laboratory parameters including the global assays have not been done to date.
The health care in India is mostly out of one's own pocket, and the victims are of the lower socio economic strata the health care costs are seldom affordable. Research in the field is also sparse due to lack of funding for the same. The investigators through this research aim to study the clinical and laboratory profile of snakebite victims presenting to a tertiary care snakebite treatment centre in central Kerala and the role of global coagulation assays in the management of the same.
Once answered, the research question, would provide a better understanding of the hematotoxic snakebite in the region.
It could aid in better patient care strategies, including possible determination of a better test for coagulopathy, judicious antivenom and blood product usage.
Its relevance in local, national and international context:.
Snakebite being region specific warrants a region specific approach to the problem. Venomous species like Humpnosed pit viper (Hypnale hypnale) envenomation which is the second most common snakebite (first being Daboia russelli ) in the region is a serious problem that needs better understanding.
This would be a model which can be replicated in selected tertiary care snakebite centers across the country. Answering these research questions across the country would lead to better understanding of coagulopathy in snakebite, its response to antivenom and blood products in India.
It may also lead to quantifying the need for region specific antivenom in the country.
No Indian study has systematically examined the changes in early laboratory tests results in envenomed and non envenomed snakebite victims to date.
With the exception of a few case reports there has been no studies that has looked at the performance of global coagulation assays in the country.
The country that becomes the largest contributor of global burden of snake bite in terms of mortality is India.
This model if applicable in India, should be replicable elsewhere too. Ten years back, the investigators would not have been able to envision this study, since the understanding of the process of snake bite related coagulopathy was limited, and it was national projects like the Australian snake bite project implemented elsewhere that form the basis for the current understanding of the problem of snakebite.
In the international context many other low and middle income countries that are burdened by snake bites would benefit from any result in terms of a better bedside coagulation test (like CWA or MLW) or a cheaper blood indices (DNI) to prognosticate snake envenomation.
The understanding of coagulopathy in snakebite is now changing. Conventionally, although this coagulopathy is likened to disseminated intravascular coagulation (DIC), in the recent years, it has been described as venom-induced consumptive coagulopathy (VICC).
VICC defers from DIC in its rapidity of both onset and resolution. It used to be compared to Disseminated Intravascular Coagulation, but now the understanding of the same is changing and more recently the term VICC- Venom induced consumptive coagulopathy has been introduced. The snake venom in India are known to contain Factor V activators (D russelli), Factor X activators (D russelli), prothrombin activators (PTA) (Echis sp.), thrombin like enzymes (TLE) and fibrinogenases (Trimeresurus sp,. Hypnale hypnale). The above mentioned findings are mostly from studies in Srilanka, with assays done in samples frozen and sent to Australia, by the same team of investigators.
There are not many properly conducted study from any region of India that helps understand the pathophysiology better.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- All patients with history suggestive of snakebite presenting within 6 hours of snakebite and providing a written informed consent and/or assent would be included in the study Definitions: 'Snakebite' OR 'History suggestive of snakebite' would be defined as, patients or their bystander claiming in sound mind not and not under the influence of any inebriants, to have witnessed being bitten by a snake, OR, patient with clinical features of snakebite as suspected by the clinician on floor
Key inclusion criteria (2 listed)
- All patients with history suggestive of snakebite presenting within 6 hours of snakebite AND
- All providing a written informed consent and/or assent
Key exclusion criteria (5 listed)
- All patients of stings or bites other than snakes
- All patients who received antivenom or blood products at another institute
- All patients with known hematological malignancies, coagulation disorders, chronic liver or renal failure.
- All patients known to be on warfarin, heparin or any newer oral or injectable anticoagulants
- All withdrawing a consent later on, or withdrawing assent later on-
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
To study the serial change in CT of snakebite victims
Time frame: up to 30 days
Change from baseline (sample taken at admission) for clotting time would be recorded in minutes and seconds assessed at 1 hour (post admission), 1 hour 30 mins (post admission), 3 hours (post admission), 6 hours (post bite), 6 hours post antivenom, 6 hours after blood products or 12 hours after antivenom and at discharge or at 30 days (whichever is earlier)
To study the serial change in fibrinogen levels of snakebite victims
Time frame: up to 30 days
The change in fibrinogen levels from baseline (sample taken at admission, 0 hour), 6 hour post bite, 6 hours post antivenom,12 hours post antivenom, 6 hours after blood products and at discharge or at 30 days (whichever occurs earlier), measured in weight per volume (milligram per decilitre).
To study the serial change in D dimer levels of snakebite victims
Time frame: up to 30 days
The change D dimer from baseline (sample taken at admission, 0 hour), 6 hour post bite, 6 hours post antivenom,12 hours post antivenom, 6 hours after blood products and at discharge or at 30 days (whichever occurs earlier) measured in weight per volume ( micrograms per decilitre respectively).
6 secondary outcomes
Diagnostic accuracy of Clotting Time in detecting coagulopathy
Time frame: 48 hours
Diagnostic accuracy of 20'WBCT, MLW, Delayed reading of 20'WBCT in detecting coagulopathy
Time frame: 48 hours
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of the bedside coagulation tests.
Time frame: 48 hours
Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation conventional coagulation tests
Time frame: 48 hours
To study the serial change in PT and aPTT-clot waveform of snakebite victims
Time frame: up to 7 days
To describe the clinical characteristics of snakebite victims measured as per a pre set proforma
Time frame: up to 30 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Mar 2024.
- Background: PubMed 30429630Abraham SV, Rafi AM, Krishnan SV, Palatty BU, Innah SJ, Johny J, Varghese S. Utility of Clot Waveform Analysis in Russell's Viper Bite Victims with Hematotoxicity. J Emerg Trauma Shock. 2018 Jul-Sep;11(3):211-216. doi: 10.4103/JETS.JETS_43_17.
- 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.
Siju V Abraham, M D principal investigator
Jubilee Mission Medical College and Research Institute
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 Snake Bites and Coagulopathy, Consumption, run by Jubilee Mission Medical College and Research Institute 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 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: finished, as of the sponsor's last update on 7 Mar 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To study the serial change in CT of snakebite victims (time frame: up to 30 days). The study lists 3 primary outcomes in all. 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 NCT04520282, which also lists 1 linked publication.
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 7 Mar 2024.