SnakebiteWISHNCT03859154
Waveform Analysis In Snakebite Victims With Hematotoxicity
An observational study of Snakebite and Coagulopathy, Consumption, run by Jubilee Mission Medical College and Research Institute at 1 site in India.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Snakebite, Coagulopathy, Consumption
- How many people
- 96 participants
- Where
- 1 siteIndia
- Study dates
- 1 Mar 2022to 30 Jun 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 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
Who may be able to join
- -snakebite victims were activated Partial Thromboplastin Time (aPTT) sample has been sent
Who cannot join
- Not consenting to be part of the study
- OR known case of coagulation disorders
- OR chronic liver disease
Trial locations and contacts
1 site in 1 country.
India1 site
Jubilee Mission Medical College and Research Institute
Thrissur, Kerala, 686012
About this study
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.
Read more
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
Read the 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)
- Conditions
- Snakebite, Coagulopathy, Consumption
- Medical subject headings
- Snake Bites, Disseminated Intravascular Coagulation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clot wave form 1st derivative changes
Changes in the 1 st derivative
Measured: 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.
Clot wave form 2nd derivative changes
Changes in the 2nd derivative
Measured: 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 delay phase, baseline, acceleration, deceleration and end point phases of CWA
Changes in the predefined Clot wave segments
Measured: 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.
Secondary outcomes (2)
Clotting time (CT)
The absolute clotting time by modified lee white method done for all samples as per institutional protocol
Measured: 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..
maximum coagulation velocity
maximum coagulation velocity
Measured: 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.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Mar 2019
- Study start1 Mar 2022
- Primary completion1 Jun 2023
- Study completion30 Jun 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 SnakebiteStudies 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
- NCT03859154
- Sponsor's protocol ID
- 05/19/IEC/JMMC&RI
- Other IDs
- U1111-1229-0385
- Acronym
- WISH
- Status last verified
- Jul 2023
- First submitted
- 26 Feb 2019
- Last updated
- 17 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- 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 17 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Waveform Analysis In Snakebite Victims With Hematotoxicity
- ClinicalTrials.gov ID
- NCT03859154
- Acronym / sponsor ID
- WISH / 05/19/IEC/JMMC&RI
- Conditions
- Snakebite, Coagulopathy, Consumption
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 96 participants (actual)
- Lead sponsor
- Jubilee Mission Medical College and Research InstituteUniversity, hospital or other
- Study start
- 1 Mar 2022 (actual)
- Primary completion
- 1 Jun 2023 (actual)
- Study completion
- 30 Jun 2023 (actual)
- First posted
- 1 Mar 2019 (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.
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
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
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- 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
Key inclusion criteria (1 listed)
- -snakebite victims were activated Partial Thromboplastin Time (aPTT) sample has been sent
Key exclusion criteria (3 listed)
- Not consenting to be part of the study
- OR known case of coagulation disorders
- OR chronic liver disease
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
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
2 secondary outcomes
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..
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.
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 17 Jul 2023.
- Results publication: 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 Snakebite 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 1 inclusion and 3 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 17 Jul 2023. 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?
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.). 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 NCT03859154, 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 17 Jul 2023.