Clinical trial NCT04520282: Hemostatic Variables In Snakebite 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
Study type: OBSERVATIONAL
Overall status: COMPLETED
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
Lead sponsor: Jubilee Mission Medical College and Research Institute
Sponsor class: OTHER
First posted: 2020-08-20
Enrollment: 96
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
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

Brief 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 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.

Eligibility criteria: Inclusion Criteria:

1. All patients with history suggestive of snakebite presenting within 6 hours of snakebite AND
2. All providing a written informed consent and/or assent

Exclusion Criteria:

1. All patients of stings or bites other than snakes
2. All patients who received antivenom or blood products at another institute
3. All patients with known hematological malignancies, coagulation disorders, chronic liver or renal failure.
4. All patients known to be on warfarin, heparin or any newer oral or injectable anticoagulants
5. All withdrawing a consent later on, or withdrawing assent later on-

Primary outcomes:
measure: To study the serial change in CT of snakebite victims
timeFrame: up to 30 days
measure: To study the serial change in fibrinogen levels of snakebite victims
timeFrame: up to 30 days
measure: To study the serial change in D dimer levels of snakebite victims
timeFrame: up to 30 days
Secondary outcomes:
measure: Diagnostic accuracy of Clotting Time in detecting coagulopathy
timeFrame: 48 hours
measure: Diagnostic accuracy of 20'WBCT, MLW, Delayed reading of 20'WBCT in detecting coagulopathy
timeFrame: 48 hours
measure: Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of the bedside coagulation tests.
timeFrame: 48 hours
measure: Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation conventional coagulation tests
timeFrame: 48 hours
measure: To study the serial change in PT and aPTT-clot waveform of snakebite victims
timeFrame: up to 7 days
measure: To describe the clinical characteristics of snakebite victims measured as per a pre set proforma
timeFrame: up to 30 days
Other outcomes:
measure: Time to envenomation in hematotoxic snakebites in the region
timeFrame: 7 days
measure: Time to envenomation in Russells viper snake bite in the region
timeFrame: 48 hours
measure: Time to envenomation in pitviper (crotaline) snake bite in the region
timeFrame: 48 hours
measure: To study the serial change in ROTEM waveform of snakebite victims
timeFrame: up to 7 days
measure: To study the serial change in PT, aPTT of snakebite victims
timeFrame: up to 30 days
measure: To study the serial change in coagulation factor assays of snakebite victims
timeFrame: up to 7 days
measure: Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of coagulation factor assays.
timeFrame: 48 hours
measure: Change in coagulopathy in snakebite victims, after antivenom administration as measured by normalisation of Clot Waveform analysis (CWA) and Rotational Thromobelastometry
timeFrame: 48 hours
measure: To study the serial change in myoglobin levels of snakebite victims
timeFrame: 7 days
measure: To study the correlation of admission proteinuria and incidence of renal failure in 30 days
timeFrame: up to 7 days
measure: To describe the peripheral smear changes in hematotoxic snakebite victims
timeFrame: up to 7 days
Locations:
city: Thrissur
country: India
facility: Jubilee Mission Medical College and Research Institute
state: Kerala
Study officials:
affiliation: Jubilee Mission Medical College and Research Institute
name: Siju V Abraham, M D
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.