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

Scorpion Sting Envenomation Clinical Trial

Official title:

Prospective, Randomized, Double-Blind, Controlled Study of Alacramyn® vs. Placebo in Pediatric Patients With Systemic Signs of Scorpion Sting Envenomation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00685230
• Other study ID #: AL-02/03
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: May 23, 2008
• Last updated: June 1, 2011
• Start date: May 2004
• Est. completion date: October 2005

Study information

• Verified date: June 2011
• Source: Instituto Bioclon S.A. de C.V.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

The purpose of this Prospective, Randomized, Double-Blind, Controlled, Multicenter Treatment Protocol, phase III trial is to examine the safety and efficacy of Alacramyn® for treatment of patients envenomed by scorpion sting.

This study will take place in two pediatric Intensive care units in Tucson, Arizona.

Patients who arrive at the emergency clinic presenting with scorpion sting symptoms will be evaluated for treatment with respect to the inclusion/exclusion criteria according to the study procedures. Only patients with clinically important systemic signs of scorpion sting envenomation will be included in the study. Baseline measures will include severity evaluation of the scorpion sting envenomation. The patient's vital signs, concomitant medication, medical history and demographic data will be collected. Blood tests will be done for haematology, chemistry, venom and anti-venom levels and urine test.

After informed consent and inclusion7exclusion criteria have been obtained and verified, and the baseline measurements have been done, three vials of Alacramyn® or placebo will be administered. During the following 3 hours, midazolam will continue, if indicated for control of agitation.

Patients off midazolam sedation after receiving study drug and no longer manifesting clinically important systemic signs of scorpion envenomation will be discharge at 4 hours, or 2 hours following cessation of midazolam drip, whichever occurs later. Prior to discharge repeat lab work, physical assessments, and vital signs will be done. Patients still requiring midazolam sedation and/or manifesting clinically important systemic signs of scorpion envenomation will be treated with standard of care for the duration of clinical symptoms. Those remaining for extended care undergo final study assessments at time of hospital discharge or at 24 hours after study drug infusion if hospitalization continues.

All patients who participated in the study will be contacted 7 and 14 days after treatment, looking for symptoms suggestive of ongoing venom effect, delayed serum sickness as well as for any other adverse event reported by the patient.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: October 2005
• Est. primary completion date: August 2005
• Accepts healthy volunteers: No
• Gender: All
• Age group: 6 Months to 18 Years

Eligibility

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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.

Related Conditions & MeSH terms

• Bites and Stings
• Poisoning
• Scorpion Sting Envenomation
• Scorpion Stings

Intervention

Biological:
• Antivenin Centruroides (scorpion) equine immune F(ab)2
3 vials of Alacramyn reconstitued in 50 ml of normal saline as a IV infusion over 10 minutes.

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

Locations

Country	Name	City	State
United States	Tucson Medical Center	Tucson	Arizona
United States	University Medical Center	Tucson	Arizona

Sponsors (3)

Lead Sponsor	Collaborator
Instituto Bioclon S.A. de C.V.	Universidad Nacional Autonoma de Mexico, University of Arizona

Country where clinical trial is conducted

United States, 

References & Publications (15)

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

Berg RA, Tarantino MD. Envenomation by the scorpion Centruroides exilicauda (C sculpturatus): severe and unusual manifestations. Pediatrics. 1991 Jun;87(6):930-3. — View Citation

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.

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

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

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. Review. — View Citation

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.

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. — View Citation

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

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

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. — View Citation

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

Rachesky IJ, Banner W Jr, Dansky J, Tong T. Treatments for Centruroides exilicauda envenomation. Am J Dis Child. 1984 Dec;138(12):1136-9. — View Citation

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

TESS Data Collection Manual (available upon request)

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary study endpoint is the resolution of clinically important signs of scorpion envenomation		4 hours
Secondary	Alacramyn®-treated patients require significantly less benzodiazepine sedation than placebo controls, for control of agitation		4 hours
Secondary	Venom blood levels decrease after Alacramyn® treatment, while the placebo group continues to have elevated blood venom levels		1 hour

External Links

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