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

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

Timeline

Start

2004-05

Primary completion

2005-08

Completion

2005-10

Outcome

Met primary endpoint

paper resolution of symptoms in all eight antivenom recipients versus one of seven placebo recipients within 4 hours after treatment (P=0.001). PMID 19439743 ↗

Publications

• Background Likes K, Banner W Jr, Chavez M. Centruroides exilicauda envenomation in Arizona. West J Med. 1984 Nov;141(5):634-7.
• 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.
• 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.
• 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.
• 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.
• 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.
• Background Rimsza ME, Zimmerman DR, Bergeson PS. Scorpion envenomation. Pediatrics. 1980 Aug;66(2):298-302.
• 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.

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Indications