A Controlled Clinical Trial on The Use of a Specific Antivenom Against Envenoming by Bungarus Multicinctus

In northern Vietnam, a vast majority of the most severe envenomed patients are bitten by Bungarus multicinctus. Hitherto, these victims have received supportive care only. The aims of this study were to assess the possible efficacy and side effects of a newly produced antivenom.

Study Overview

• Status: Completed
• Conditions: Snake Bite
• Intervention / Treatment: Other: Supportive Care; Drug: Bungarus multicinctus-candidus Antivenom

Detailed Description

Venomous snakebites constitute a serious health problem in many Asian countries. In Vietnam, the burden of snakebite on the public health stimulated Calmette to conduct original studies at the Vaccine Institute in Saigon over a hundred years ago and to develop the first snake antivenom ever.

In northern Vietnam, a vast majority of the most severe envenomed patients are bitten by Bungarus multicinctus, which is the only krait species giving rise to significant morbidity and mortality in the area. Its venom contains toxins which can cause severe neuromuscular blockade but which do not give rise to swelling or necrosis at the site of the bite.

Supportive care is an important part of the management of snakebites, but antivenom administration is the mainstay therapy in the majority of medically significant envenomings. Such specific therapy may dramatically reduce the consequences of the envenomation. In Vietnam, no specific antivenom against B. multicinctus has been available until recently when it has produced for clinical use.

• Study Type: Interventional
• Enrollment (Actual): 81
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Vietnam
  • Hanoi, Vietnam
    • Vietnam Poison Control Center, Bach Mai Hospital, HMU

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Envenomed by B. multicinctus
• Showed clinical signs of systemic envenomation (neuromuscular signs)
• Provided written informed consent (during the year 2006)

Exclusion Criteria:

• Pregnancy
• Patients had a known history of intolerance to equine serum

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: control group; As the antivenom was not yet clinically available until 2006, all patients included during the first two years (2004-2005) received supportive therapy only.	Other: Supportive Care; Supportive Care only (endotracheal intubation, mechanical ventilation...)
Active Comparator: antivenom group; The patients included during the third year (2006) were treated with antivenom therapy and supportive care.	Drug: Bungarus multicinctus-candidus Antivenom; Five to ten ampoules of antivenom, depending on severity of muscle paralysis, were diluted with isotonic glucose solution to have total 50 ml and infused intravenously by electric pump during one hour. After a period of 6-8 hours, a second infusion was administered, under similar condition to the first, if no clinical improvement or adverse reaction had been noted. The patients also received supportive care such as intubation, ventilation...if necessary.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
duration of mechanical ventilation	the length of ICU stay

Secondary Outcome Measures

Outcome Measure	Time Frame
clinical course during ICU stay	the length of ICU stay
complications (Ventilator associated pneumonia...)	the length of ICU stay
adverse effects (anaphylaxis, serum sickness...)	the length of ICU stay
hyponatremia, renal and liver function	the length of ICU stay

Collaborators and Investigators

• Sponsor: Hanoi Medical University
• Collaborators: Karolinska Institutet; Swedish International Development Cooperation Agency (SIDA)
• Investigators: Study Director: Jonas Höjer, MD, PhD, Karorinska Institute, Swedish Poisons Information Centre

Publications and helpful links

General Publications

• Chan JC, Cockram CS, Buckley T, Young K, Kay R, Tomlinson B. Evenoming by Bungarus multicinctus (many-banded krait) in Hong Kong. J Trop Med Hyg. 1995 Dec;98(6):457-60.
• Pe T, Myint T, Htut A, Htut T, Myint AA, Aung NN. Envenoming by Chinese krait (Bungarus multicinctus) and banded krait (B. fasciatus) in Myanmar. Trans R Soc Trop Med Hyg. 1997 Nov-Dec;91(6):686-8. doi: 10.1016/s0035-9203(97)90524-1.
• Cheng AC, Winkel KD. Snakebite and antivenoms in the Asia-Pacific: wokabaut wantaim, raka hebou ("walking together"). Med J Aust. 2001 Dec 3-17;175(11-12):648-51. doi: 10.5694/j.1326-5377.2001.tb143762.x. No abstract available.
• Dart RC, McNally J. Efficacy, safety, and use of snake antivenoms in the United States. Ann Emerg Med. 2001 Feb;37(2):181-8. doi: 10.1067/mem.2001.113372.
• White J. Envenoming and antivenom use in Australia. Toxicon. 1998 Nov;36(11):1483-92. doi: 10.1016/s0041-0101(98)00138-x.
• Karlson-Stiber C, Persson H, Heath A, Smith D, al-Abdulla IH, Sjostrom L. First clinical experiences with specific sheep Fab fragments in snake bite. Report of a multicentre study of Vipera berus envenoming. J Intern Med. 1997 Jan;241(1):53-8. doi: 10.1046/j.1365-2796.1997.80896000.x.
• Ha TH, Hojer J, Trinh XK, Nguyen TD. A controlled clinical trial of a novel antivenom in patients envenomed by Bungarus multicinctus. J Med Toxicol. 2010 Dec;6(4):393-7. doi: 10.1007/s13181-010-0051-4.

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): December 1, 2006
• Study Completion (Actual): December 1, 2006

Study Registration Dates

• First Submitted: December 16, 2008
• First Submitted That Met QC Criteria: December 17, 2008
• First Posted (Estimate): December 18, 2008

Study Record Updates

• Last Update Posted (Estimate): December 18, 2008
• Last Update Submitted That Met QC Criteria: December 17, 2008
• Last Verified: December 1, 2008

More Information

Terms related to this study

• Keywords: antivenom; snake bite; Bungarus multicinctus; Vietnam
• Additional Relevant MeSH Terms: Chemically-Induced Disorders; Wounds and Injuries; Poisoning; Bites and Stings; Snake Bites; Physiological Effects of Drugs; Immunologic Factors; Antivenins
• Other Study ID Numbers: antivenom; second study on snakebite

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No