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

NCT ID: NCT00685230

Last Updated: 2011-06-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2/PHASE3

Total Enrollment

15 participants

Study Classification

INTERVENTIONAL

Study Start Date

2004-05-31

Study Completion Date

2005-10-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Scorpion Sting Envenomation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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1

Alacramyn and midazolam as needed

Group Type EXPERIMENTAL

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

Intervention Type BIOLOGICAL

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

2

placebo and midazolam as needed

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type OTHER

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

Interventions

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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.

Intervention Type BIOLOGICAL

Placebo

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

Intervention Type OTHER

Other Intervention Names

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Anascorp

Eligibility Criteria

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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.
Minimum Eligible Age

6 Months

Maximum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Arizona

OTHER

Sponsor Role collaborator

Universidad Nacional Autonoma de Mexico

OTHER

Sponsor Role collaborator

Instituto Bioclon S.A. de C.V.

INDUSTRY

Sponsor Role lead

Responsible Party

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Instituto Bioclon

Principal Investigators

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Leslie Boyer, MD

Role: PRINCIPAL_INVESTIGATOR

Poison and Drug Center

Walter Garcia, MD

Role: STUDY_DIRECTOR

Instituto Bioclon S.A. de C.V.

Alejandro Alagon, PhD

Role: STUDY_CHAIR

Universidad Nacional Autonoma de Mexico

Locations

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Tucson Medical Center

Tucson, Arizona, United States

Site Status

University Medical Center

Tucson, Arizona, United States

Site Status

Countries

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United States

References

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

Reference Type BACKGROUND
PMID: 6516334 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 10533010 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6381751 (View on PubMed)

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

Reference Type BACKGROUND

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

Reference Type 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.

Reference Type BACKGROUND
PMID: 10533009 (View on PubMed)

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

Reference Type 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.

Reference Type BACKGROUND

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

Reference Type 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.

Reference Type BACKGROUND

TESS Data Collection Manual (available upon request)

Reference Type 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.

Reference Type BACKGROUND
PMID: 2034501 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 6507396 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 7402816 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19439743 (View on PubMed)

Related Links

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http://www.arizona.edu/

The University of Arizona

http://www.ibt.unam.mx

Instituto de Biotecnologia de la UNAM

Other Identifiers

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AL-02/03

Identifier Type: -

Identifier Source: org_study_id

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