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

Study Overview
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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: The investigational antivenom is safe as treatment of scorpion sting envenomation. 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.

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

Conditions
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Scorpion Sting Envenomation

Intervention / Treatment
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* Biological: Antivenin Centruroides (scorpion) equine immune F(ab)2
* Other: Placebo


Participation Criteria
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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.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Alacramyn and midazolam as needed | Biological: Antivenin Centruroides (scorpion) equine immune F(ab)2<br>* 3 vials of Alacramyn reconstitued in 50 ml of normal saline as a IV infusion over 10 minutes.<br>* Other names: Anascorp;|
| Placebo Comparator: 2<br>placebo and midazolam as needed | Other: Placebo<br>* Placebo reconstituted in 50 ml of normal saline administered over 10 min<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary study endpoint is the resolution of clinically important signs of scorpion envenomation |  | 4 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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scorpion sting, envenomation, alacramyn