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

Purpose

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.

Condition	Intervention	Phase
Snake Bite	Drug: Bungarus multicinctus-candidus Antivenom Other: Supportive Care	Phase 1 Phase 2

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	A Controlled Clinical Trial on The Use of a Specific Antivenom Against Envenoming by Bungarus Multicinctus

Further study details as provided by Hanoi Medical University:

Primary Outcome Measures:

duration of mechanical ventilation [ Time Frame: the length of ICU stay ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

clinical course during ICU stay [ Time Frame: the length of ICU stay ] [ Designated as safety issue: Yes ]
complications (Ventilator associated pneumonia...) [ Time Frame: the length of ICU stay ] [ Designated as safety issue: Yes ]
adverse effects (anaphylaxis, serum sickness...) [ Time Frame: the length of ICU stay ] [ Designated as safety issue: Yes ]
hyponatremia, renal and liver function [ Time Frame: the length of ICU stay ] [ Designated as safety issue: Yes ]

Enrollment:	81
Study Start Date:	March 2004
Study Completion Date:	December 2006
Primary Completion Date:	December 2006 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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.

Arms

Assigned Interventions

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.

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.

Eligibility

Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00811239

Locations

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

Sponsors and Collaborators

Hanoi Medical University

Karolinska Institutet

Swedish International Development Cooperation Agency (SIDA)

Investigators

Study Director:

Jonas Höjer, MD, PhD

Karorinska Institute, Swedish Poisons Information Centre

More Information

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.

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. 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. Review.

White J. Envenoming and antivenom use in Australia. Toxicon. 1998 Nov;36(11):1483-92.

Karlson-Stiber C, Persson H, Heath A, Smith D, al-Abdulla IH, Sjöström 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.

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Ha TH, Höjer 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.

ClinicalTrials.gov Identifier:	NCT00811239 History of Changes
Other Study ID Numbers:	antivenom, second study on snakebite
Study First Received:	December 16, 2008
Last Updated:	December 17, 2008
Health Authority:	Vietnam: Ministry of Health

Keywords provided by Hanoi Medical University:

antivenom
snake bite
Bungarus multicinctus
Vietnam

Additional relevant MeSH terms:

Snake Bites
Bites and Stings
Poisoning
Substance-Related Disorders

Antivenins
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on June 17, 2013