Optimal Dose of Antivenom for Daboia Siamensis Envenomings

NCT04210141 | Suspended Phase 2 DMC

• 1 other identifier: OXTREC 63-19
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of the study is to identify an 'optimal' initial dosing of the new Burma Pharmaceutical Industry (BPI) lyophilized mono-specific antivenom for patients with systemic Daboia siamensis envenoming. The initial dosing will aim to reverse venom-induced coagulopathy (as demonstrated by a negative 20 minutes Whole Blood Clotting Time (20WBCT) at 6 hours in 95% of patients whilst causing less than 5% anaphylactic reaction.

Conditions

Daboia Siamensis Envenoming

Outcome Measures

Primary Outcomes (2)

• Blood Coagulation

  Blood coagulation at 6 hours as measured by the 20 minute WBCT (binary outcome)

  within 24 hours of patient recruitment

• Anaphylaxis

  Anaphylaxis as defined by the European Academy of Allergy and Immunology within 180 minutes of antivenom administration

  within 24 hours of patient recruitment

Secondary Outcomes (7)

• Time to restoration of blood coagulability as determined by the 20 WBCT.

  within 24 hours of patient recruitment

• International normalized ratio (INR) determined by the POC INR meter.

  within 24 hours of patient recruitment

• Blood coagulability as determined by PT and fibrinogen

  within 24 hours of patient recruitment

• Occurrence of any serious adverse events

  within 24 hours of patient recruitment

• The occurrence of envenoming sequelae at 3 month follow up

  within 6 months of patient recruitment

Study Arms (2)

Standard of care

ACTIVE COMPARATOR

Patients will receive an initial antivenom dose of 80mL lyophilized BPI viper antivenom, as per current national guidelines

Biological: lyophilized BPI viper antivenom

Adaptive arm

EXPERIMENTAL

Patients will receive an initial dose of lyophilized BPI viper antivenom determined by the adaptive model.

Biological: lyophilized BPI viper antivenom

Interventions

lyophilized BPI viper antivenom BIOLOGICAL

Antivenom

Adaptive arm; Standard of care

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients suspected of systemic envenoming with DS
• Incoagulable blood by 20-minute WBCT
• Antivenom naïve
• Age ≥ 15

You may not qualify if:

• Receiving anticoagulant therapy e.g. warfarin
• Known bleeding disorder e.g. haemophilia
• Decompensated liver disease
• Severely envenomed patients (as defined in the Myanmar National Guidelines)

Sponsors & Collaborators

• Myanmar Oxford Clinical Research Unit: lead
• University of Oxford: collaborator
• Mahidol Oxford Tropical Medicine Research Unit: collaborator

Study Sites (1)

Myanmar Oxford Clinical Research Unit

Yangon, Burma

Location

Related Publications (5)

• Gutierrez JM, Calvete JJ, Habib AG, Harrison RA, Williams DJ, Warrell DA. Snakebite envenoming. Nat Rev Dis Primers. 2017 Sep 14;3:17063. doi: 10.1038/nrdp.2017.63.

  PMID: 28905944 BACKGROUND

• Williams DJ, Faiz MA, Abela-Ridder B, Ainsworth S, Bulfone TC, Nickerson AD, Habib AG, Junghanss T, Fan HW, Turner M, Harrison RA, Warrell DA. Strategy for a globally coordinated response to a priority neglected tropical disease: Snakebite envenoming. PLoS Negl Trop Dis. 2019 Feb 21;13(2):e0007059. doi: 10.1371/journal.pntd.0007059. eCollection 2019 Feb. No abstract available.

  PMID: 30789906 BACKGROUND

• Myint-Lwin, Warrell DA, Phillips RE, Tin-Nu-Swe, Tun-Pe, Maung-Maung-Lay. Bites by Russell's viper (Vipera russelli siamensis) in Burma: haemostatic, vascular, and renal disturbances and response to treatment. Lancet. 1985 Dec 7;2(8467):1259-64. doi: 10.1016/s0140-6736(85)91550-8.

  PMID: 2866333 BACKGROUND

• Alfred S, Bates D, White J, Mahmood MA, Warrell DA, Thwin KT, Thein MM, Sint San SS, Myint YL, Swe HK, Kyaw KM, Zaw A, Peh CA. Acute Kidney Injury Following Eastern Russell's Viper (Daboia siamensis) Snakebite in Myanmar. Kidney Int Rep. 2019 May 29;4(9):1337-1341. doi: 10.1016/j.ekir.2019.05.017. eCollection 2019 Sep. No abstract available.

  PMID: 31517153 BACKGROUND

• Wheeler GM, Mander AP, Bedding A, Brock K, Cornelius V, Grieve AP, Jaki T, Love SB, Odondi L, Weir CJ, Yap C, Bond SJ. How to design a dose-finding study using the continual reassessment method. BMC Med Res Methodol. 2019 Jan 18;19(1):18. doi: 10.1186/s12874-018-0638-z.

  PMID: 30658575 BACKGROUND

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomized adaptive design

Study Record Dates

• First Submitted: December 20, 2019
• First Posted: December 24, 2019
• Study Start: April 1, 2025
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): November 1, 2027
• Last Updated: April 1, 2024

Record last verified: 2023-10

Locations

BU (1)