Double-Blind, Alacramyn® vs. Placebo in Pediatric Patients

NCT00685230 | Completed Phase 2

• 1 other identifier: AL-02/03
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

Brief Summary

There is no FDA approved therapy for the treatment of scorpion envenomation, Centruroides scorpion envenomation produces a pattern of neurotoxicity with a spectrum of severity ranging from trivial to life threatening. Patients stung by Centruroides scorpions develop a clinical syndrome which may require sedation with benzodiazepines and observation for 6 to 28 hours of intensive care monitoring. A safe therapy is necessary to halt the progression of symptoms early in the clinical course while avoiding the clinical deterioration that can occur en route to a tertiary facility. Alacramyn® is anticipated to be safer and more effective than the present standard of care, midazolam, and faster-acting such that the need for transport of most rural patients will be eliminated and will reduce hospitalization time. The working hypotheses are as follows:

1. 1.The investigational antivenom is safe as treatment of scorpion sting envenomation.
2. 2.The investigational antivenom is effective as treatment of scorpion sting envenomation.

Conditions

Scorpion Sting Envenomation

Keywords

scorpion sting; envenomation; alacramyn

Outcome Measures

Primary Outcomes (1)

• The primary study endpoint is the resolution of clinically important signs of scorpion envenomation

  4 hours

Secondary Outcomes (2)

• Alacramyn®-treated patients require significantly less benzodiazepine sedation than placebo controls, for control of agitation

  4 hours

• Venom blood levels decrease after Alacramyn® treatment, while the placebo group continues to have elevated blood venom levels

  1 hour

Study Arms (2)

1

EXPERIMENTAL

Alacramyn and midazolam as needed

Biological: Antivenin Centruroides (scorpion) equine immune F(ab)2

2

PLACEBO COMPARATOR

placebo and midazolam as needed

Other: Placebo

Interventions

Antivenin Centruroides (scorpion) equine immune F(ab)2 BIOLOGICAL

3 vials of Alacramyn reconstitued in 50 ml of normal saline as a IV infusion over 10 minutes.

Also known as: Anascorp

1

Placebo OTHER

Placebo reconstituted in 50 ml of normal saline administered over 10 min

2

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females of 6 months to 18 years of age
• Presenting for emergency treatment within 5 hours with clinically important systemic signs of scorpion sting envenomation.
• Signed written Informed Consent by patient or legal guardian.
• No participation in a clinical drug trial within the last month or concomitantly.

You may not qualify if:

• Allergy to horse serum.
• Use within the past 24 hours of drugs expected to alter immune response: H1 or H2 blockers, corticosteroids.
• Use of any antivenom within the last month or concomitantly.
• Underlying medical conditions that significantly alter immune response: bone marrow suppression congenital or acquired immuno-deficiency state, chemotherapy and chronic corticosteroid use.
• Allergy to midazolam.
• More than 0.3mg/kg of body weight of midazolam administered during the hour prior to study drug infusion.
• Concurrent medical condition involving a baseline neurologic status mimicking envenomation (chorea, tardive dyskinesia, uncontrolled epilepsy).
• Pregnant and nursing women.

Sponsors & Collaborators

• Instituto Bioclon S.A. de C.V.: lead
• University of Arizona: collaborator
• Universidad Nacional Autonoma de Mexico: collaborator

Study Sites (2)

Tucson Medical Center

Tucson, Arizona, 85712, United States

Location

University Medical Center

Tucson, Arizona, 85724, United States

Location

Related Publications (16)

• Likes K, Banner W Jr, Chavez M. Centruroides exilicauda envenomation in Arizona. West J Med. 1984 Nov;141(5):634-7.

  PMID: 6516334 BACKGROUND

• Connor, D.A., Seldon, B.S., Scorpion Envenomation. Chapter in Wilderness Medicine; Management of Wilderness and Environmental Emergencies. 3rd edition. Auerbach PS, ed., Mosby Yearbook, Inc. St. Louis, MO. pp 831-842

  BACKGROUND

• Gibly R, Williams M, Walter FG, McNally J, Conroy C, Berg RA. Continuous intravenous midazolam infusion for Centruroides exilicauda scorpion envenomation. Ann Emerg Med. 1999 Nov;34(5):620-5. doi: 10.1016/s0196-0644(99)70164-2.

  PMID: 10533010 BACKGROUND

• Curry SC, Vance MV, Ryan PJ, Kunkel DB, Northey WT. Envenomation by the scorpion Centruroides sculpturatus. J Toxicol Clin Toxicol. 1983-1984;21(4-5):417-49. doi: 10.3109/15563658308990433.

  PMID: 6381751 BACKGROUND

• Chavez-Haro A., Gonzalez J., Paniagua nJ., Efficiency and Security Comparison between Two Different Scorpion-derived Antivenom in Mexico, Abstract, Leon Study Data Analysis.

  BACKGROUND

• Gonzalez, C., et al, Development of an Immunoenzymatic Assay for the Quantification of Scorpion Venom in Plasma, Abstract, Cuernavaca, 2000

  BACKGROUND

• LoVecchio F, Welch S, Klemens J, Curry SC, Thomas R. Incidence of immediate and delayed hypersensitivity to Centruroides antivenom. Ann Emerg Med. 1999 Nov;34(5):615-9. doi: 10.1016/s0196-0644(99)70176-9.

  PMID: 10533009 BACKGROUND

• Alagon Cano, A., Gozalez Juarez, C., From Serotherapy to Fabotherapy, Abstract, Cuernavaca, 1998.

  BACKGROUND

• Cabral-Soto, J., et al, Comparison of Efficacy between Two Antiscorpion Antivenoms, Abstract, Cuernavaca, 2000, Clinical Study Report, Randomized, Double-Blind, Variable dosing of Alacramyn in Patients With Scorpion Sting (this was done with two approved products in Mexico, Alacramyn and Birmex), March 2002.

  BACKGROUND

• Madrazo Navarro, M., et al, Animales Ponzoñosos en la Población Derechohabiente del IMSS 1990-1996.

  BACKGROUND

• Dart, R.C., Horowitz, R.S., Use of Antibodies as Antivenoms: A primitive Solution for Complex Problem? Rocky Mountain Poison and Drug Center, Denver Co, USA.

  BACKGROUND

• TESS Data Collection Manual (available upon request)

  BACKGROUND

• Berg RA, Tarantino MD. Envenomation by the scorpion Centruroides exilicauda (C sculpturatus): severe and unusual manifestations. Pediatrics. 1991 Jun;87(6):930-3. No abstract available.

  PMID: 2034501 BACKGROUND

• Rachesky IJ, Banner W Jr, Dansky J, Tong T. Treatments for Centruroides exilicauda envenomation. Am J Dis Child. 1984 Dec;138(12):1136-9. doi: 10.1001/archpedi.1984.02140500042015.

  PMID: 6507396 BACKGROUND

• Rimsza ME, Zimmerman DR, Bergeson PS. Scorpion envenomation. Pediatrics. 1980 Aug;66(2):298-302.

  PMID: 7402816 BACKGROUND

• Boyer LV, Theodorou AA, Berg RA, Mallie J; Arizona Envenomation Investigators; Chavez-Mendez A, Garcia-Ubbelohde W, Hardiman S, Alagon A. Antivenom for critically ill children with neurotoxicity from scorpion stings. N Engl J Med. 2009 May 14;360(20):2090-8. doi: 10.1056/NEJMoa0808455.

  PMID: 19439743 DERIVED

Related Links

• The University of Arizona
• Instituto de Biotecnologia de la UNAM

MeSH Terms

Conditions

Scorpion Stings

Condition Hierarchy (Ancestors)

Bites and Stings; Poisoning; Chemically-Induced Disorders; Wounds and Injuries

Study Officials

• Leslie Boyer, MD

  Poison and Drug Center

  PRINCIPAL INVESTIGATOR

• Walter Garcia, MD

  Instituto Bioclon S.A. de C.V.

  STUDY DIRECTOR

• Alejandro Alagon, PhD

  Universidad Nacional Autonoma de Mexico

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: May 23, 2008
• First Posted: May 28, 2008
• Study Start: May 1, 2004
• Primary Completion: August 1, 2005
• Study Completion: October 1, 2005
• Last Updated: June 2, 2011

Record last verified: 2011-06

Locations

US (2)