Waveform Analysis In Snakebite Victims With Hematotoxicity (WISH)

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ClinicalTrials.gov Identifier: NCT03859154

Recruitment Status : Recruiting

First Posted : March 1, 2019

Last Update Posted : June 1, 2020

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Sponsor:

Information provided by (Responsible Party):

Siju V Abraham, MD, Jubilee Mission Medical College and Research Institute

Study Description

Brief Summary:

In hematotoxic snakebites, due to the lack of a better alternative, 20 minute whole blood clotting test (20'WBCT) or Clotting time remains the standard test in developing countries even though its reliability and sensitivity has been shown to be low.

Activated partial thromboplastin time (aPTT) based Clot Waveform Analysis (CWA) is an optic absorbance assay that can be used as a global clotting test.

It essentially detects the change in colour of the plasma as coagulation progresses and quantifies the change in the form of a waveform.

In this study, the investigators intend to study prospectively the behaviour of clot wave (CW) in hematotoxic bites.

A pilot observational study was initially conducted (IEC Ref No. 42/16/IEC/JMMC and RI) and CWA showed changes which provided information earlier than the conventional coagulation studies in the snakebite victims studied.

While aPTT or WBCT reflects clotting time, CWA conveys the dynamic process of clot formation. CWA may reveal disorders of clotting in snakebite victims before the conventional tests become abnormal.

Here the investigators aim to study the changes in CWA in snakebite victims who develop coagulation disorders in blood

Condition or disease
Snakebite Coagulopathy, Consumption

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Detailed Description:

Viperidae bites are quite common in India and are notorious to cause hematotoxicity.

In hematotoxic bites, the test recommended to ascertain the development of coagulopathy is a whole blood clotting test (WBCT) as per the current guidelines.

Eventhough the reliability and sensitivity of WBCT has been shown to be low, it still remains the standard test.

There exists a need to explore other coagulation studies in snakebite to look for a better and efficient alternative.

Clot waveform analysis (CWA) is an activated partial thromboplastin time (aPTT)-based optic absorbance assay that can be used as a global clotting test.

It has been shown useful in identifying disseminated intravascular coagulation (DIC) in sepsis with high specificity (97.6%) and sensitivity (98%), and the test is recommended by the British Committee for Standards in Hematology guidelines for the diagnosis and treatment of DIC.

CWA is based on the traditional aPTT assay. On assessing aPTT with light transmission, a change in the light absorbance is observed as the clot stabilizes by fibrin polymerization.

Plotting the milliabsorbance (mAbs) of the sample to time, a curve is obtained which reflects the optical profile that is generated as a clot is formed.

This tracing against time gives a qualitative assessment of fibrin polymerization.

The delta in absorbance (dAbs) is based on the change in mAbs value from the baseline to the endpoint (plateau) along the Y-axis of the clot curve. The dAbs values of <100 mAbs denote low fibrinogen samples

The normal clot waveform has five main phases: delay, baseline, acceleration, deceleration, and end point.

The "delay" period begins at 0 and precedes the "baseline." which denotes the mixing of the reagents and system optimization of light intensity.

The "baseline" is the portion of the curve which appears after all reagents have been added to the time and the clot formation begins.

The aPTT value is noted at this point (vertical red line). The "acceleration" phase denotes fibrin clot formation, whereas "deceleration" denotes decreasing rate of clot formation.

There are two more curves that are plotted in CWA, the first derivative and the second derivatives. They are both derivatives of the absorbance curves. The first derivative reflects the coagulation velocity, whereas the second derivative reflects the acceleration of coagulation.

The investigators in this study aim to assess the changes in the CW form in viper-envenomated victims and to compare CWA with standard tests such as prothrombin time (PT) with the international normalized ratio (INR), aPTT, clotting time (CT) (modified Lee and White method) and 20'WBCT( twenty minute whole blood clotting test)

Study Design

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Study Type :	Observational
Estimated Enrollment :	100 participants
Observational Model:	Cohort
Time Perspective:	Prospective
Official Title:	Waveform Analysis In Snakebite Victims With Hematotoxicity
Actual Study Start Date :	April 30, 2019
Estimated Primary Completion Date :	December 1, 2020
Estimated Study Completion Date :	January 31, 2021

Groups and Cohorts

Group/Cohort
Viper bite victims Snakebite victims in whom the snake has been brought and positively identified as Viperidae AND simultaneous aPTT has been sent AND consenting to be part of the study
Nonvenomous snakebite age and gender matched victims of snake bite in whom the culprit snake brought along has been identified as a non venomous one. AND consenting to be part of the study

Outcome Measures

Primary Outcome Measures :

Clot wave form 1st derivative changes [ Time Frame: For all aPTT samples done at admission, just prior to antivenom administration, 6 hours after antivenom administration completion and 6 hours after blood product administration, upto 7 days post admission. ]
Changes in the 1 st derivative
Clot wave form 2nd derivative changes [ Time Frame: For all aPTT samples done at admission, just prior to antivenom administration, 6 hours after antivenom administration completion and 6 hours after blood product administration, up to 7 days post admission. ]
Changes in the 2nd derivative
changes in delay phase, baseline, acceleration, deceleration and end point phases of CWA [ Time Frame: For all aPTT samples done at admission, just prior to antivenom administration, 6 hours after antivenom administration completion and 6 hours after blood product administration, up to 7 days post admission. ]
Changes in the predefined Clot wave segments

Secondary Outcome Measures :

Clotting time (CT) [ Time Frame: For all CT samples done at admission, just prior to antivenom administration, 6 hours after antivenom administration completion and 6 hours after blood product administration, up to 7 days post admission.. ]
The absolute clotting time by modified lee white method done for all samples as per institutional protocol
maximum coagulation velocity [ Time Frame: For all aPTT samples done at admission, just prior to antivenom administration, 6 hours after antivenom administration completion and 6 hours after blood product administration, up to 7 days post admission. ]
maximum coagulation velocity

Other Outcome Measures:

sensitivity and specificity of CWA in detecting envenomation compared to 20'WBCT and MLW (Modified Lee and White) method [ Time Frame: from admission till time of objective detection of coagulopathy, or up to 48 hours of admission, whichever is earliest ]
To test how sensitive and specific changes in CWA is in detecting coagulopathy in snakebite victims compared to the World Health Organisation Recommended twenty minute whole blood clotting test and the modified lee white clotting time done as per institute protocol
correlation of CWA with serum fibrinogen levels [ Time Frame: For all serum Fibrinogen and aPTT sample sent simultaneously upto 48 hours of admission. ]
For all serum Fibrinogen and aPTT sample sent simultaneously correlation of CWA parameters with serum fibrinogen levels

Eligibility Criteria

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Ages Eligible for Study:	Child, Adult, Older Adult
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No
Sampling Method:	Probability Sample

Study Population

All victims of snakebite consenting to be part of the study presenting to the emergency department at Jubilee Mission Medical College and Research Institute Thrissur, Kerala, India

Snake bite registry would be established All consecutive cases would be enrolled in the study if they consent to be part of it.

Sub group analysis excluding the dry bites,would be done Sub group analysis of the victims of hematotoxic snakebite would be done

Criteria

Inclusion Criteria:

-snakebite victims were activated Partial Thromboplastin Time (aPTT) sample has been sent

Exclusion Criteria:

Not consenting to be part of the study
OR known case of coagulation disorders
OR chronic liver disease

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03859154

Contacts

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Contact: Siju V Abraham, M.D	919447754321	sijuvabraham@jmmc.ac.in

Locations

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India
Jubilee Mission Medical College and Research Institute	Recruiting
Thrissur, Kerala, India, 686012
Contact: Siju Varghese Abraham, MD +919447754311 sijuvabraham@gmail.com

Sponsors and Collaborators

Jubilee Mission Medical College and Research Institute

Investigators

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Principal Investigator:	Siju V Abraham, M.D	Jubilee Mission Medical College and Research Institute

More Information

Publications of Results:

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.

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Responsible Party:	Siju V Abraham, MD, Assistant Professor in the Department of Emergency Medicine, Jubilee Mission Medical College and Research Institute
ClinicalTrials.gov Identifier:	NCT03859154
Other Study ID Numbers:	05/19/IEC/JMMC&RI U1111-1229-0385 ( Other Identifier: World Health Organisation )
First Posted:	March 1, 2019 Key Record Dates
Last Update Posted:	June 1, 2020
Last Verified:	May 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	Undecided

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Additional relevant MeSH terms:

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Disseminated Intravascular Coagulation Snake Bites Blood Coagulation Disorders Hematologic Diseases Hemorrhagic Disorders	Bites and Stings Poisoning Chemically-Induced Disorders Wounds and Injuries Thrombophilia

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