Randomized, Double-Blind, Placebo-Controlled Study: CroFab® vs Placebo for Copperhead Snake Envenomation

Study Overview
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Brief Summary
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This study will evaluate the recovery from copperhead snake bite in patients with mild or moderate venom effect. Potential subjects received CroFab antivenom or placebo. After blinded treatment and discharge, the subject returns to the clinic for follow-up assessments at day 3, 7, 14, and 28 after snake bite as well as follow-up telephone assessments on day 10, 17, and 24 after snake bite. The purpose of this study is to compare recovery in copperhead snake bite patients treated with antivenom vs placebo (no active drug) as measured by the Patient Specific Functional Scale (PSFS) at Day 14 follow-up. The primary efficacy endpoint of this study was achieved.

Detailed Description
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This study will evaluate the recovery from copperhead snake bite in patients with mild or moderate venom effect. Potential subjects will receive CroFab antivenom or placebo. The trial is conducted by emergency room doctors, toxicologists, or surgeons at hospitals in regions where copperhead bites are common. After blinded treatment and discharge, the subject returns to the clinic for follow-up assessments at day 3, 7, 14, and 28 after snake bite. The subject will also be called by telephone for follow-up assessments on day 10, 17, and 24 after snake bite. The purpose of this study is to compare recovery in copperhead snake bite patients treated with antivenom vs placebo (no active drug) as measured by the Patient Specific Functional Scale (PSFS) at Day 14 follow-up.The primary efficacy endpoint of this study was achieved. Treatment with CroFab® demonstrated measurable and significant improvement (less disability) over placebo: in the mITT population, the LS mean total score on the PSFS at Day 14 follow-up and treatment showed less disability in patients randomized to receive CroFab® than those receiving placebo.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled Study Comparing CroFab® vs Placebo With Rescue Treatment for Copperhead Snake Envenomation

Conditions
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Snake Bites

Intervention / Treatment
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* Biological: Crotalidae polyvalent immune fab (ovine)
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria- Envenomation by a copperhead snake a. Snake identified by one of the following means: i.Snake or photograph of snake brought to Emergency Department ii.Patient chooses copperhead from an array of snake photographs iii.Patient envenomated in an area where only copperheads are endemic iv.Patient envenomated by a captive copperhead snake Completion of informed consent and eligibility confirmation within 24 hours of envenomation Envenomation on only one extremity, distal to the elbow or knee Clinical evidence of mild or moderate venom effect (limb swelling and/or tenderness) is present (Venom effects need not be progressing.) Patient willing and able to complete follow-up schedule of assessments Patient is able to read, comprehend and sign the IRB approved consent document(s) Patient is able to read and comprehend the written assessment tools (e.g., DASH, LEFS, PROMIS Physical Function Short Form 10a (PROMIS PF-10), PGIC, etc.) Patient is ≥12 years of age Patient is sober, competent, and able to complete verbal and written informed consent Exclusion Criteria- Patient has clinical evidence of severe venom effect as defined by meeting any one of the following parameters: i. Swelling to an entire extremity (all major joints affected) Lower extremity: swelling crossing hip joint Upper extremity: swelling crossing shoulder joint ii. INR > 2.0 iii. Platelets <50,000 cells / µL iv. Fibrinogen <50 mg/dL v. Compartment syndrome vi. Systolic Blood Pressure <90 mmHg vii. More than minimal bleeding viii. Investigator's clinical discretion Patient has already received antivenom for the management of the current envenomation Patient is pregnant or breastfeeding Patient is a prisoner Patient has a distracting injury or condition with acute pain or functional impairment, and/or is unable to make a reliable self-report of functionality status based solely on the condition of interest Patient had a previous snake envenomation to any body area in the 30 days prior to screening/enrollment, regardless of whether antivenom was administered for the previous envenomation Patient had an acute traumatic event, surgery, an acute medical event, or exacerbation of a pre-existing medical or surgical condition affecting the envenomated extremity within the 30 days prior to screening/enrollment Patient has participated in a clinical study involving an investigational pharmaceutical product or device within the 3 months prior to screening that may have impact on clinical outcomes of snakebite Patient has previously participated in this clinical study Patient has a known history of hypersensitivity to any components of CroFab®, or to papaya or papain Patient is otherwise unsuitable for inclusion in this study, based on the opinion of the Investigator

Ages Eligible for Study
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Minimum Age: 12 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: CroFab<br>crotalidae polyvalent immune fab (ovine) per approved labeling | Biological: Crotalidae polyvalent immune fab (ovine)<br>* crotalidae antivenom<br>* Other names: CroFab;|
| Placebo Comparator: Saline placebo<br>Saline placebo | Biological: Placebo<br>* Saline placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient Specific Functional Scale Score | Patient Specific Functional Scale (PSFS) at 14 day follow-up This is a three-item instrument, administered verbally, that is used to evaluate whether a health condition impacts a patient's ability to perform activities that are important to him/her. On the initial assessment, the patient is asked to identify up to three important activities that you are unable to do or are having difficulty with as a result of your (snakebite). The patient then provides a rating for each item, on an 11-point ordinal scale ranging from 0 (unable to perform activity) to 10 (able to perform activity at the same level as before the injury or problem). During reassessments, the subject is prompted to re-rate the same three activities. The average of up to 3 specific activity scores was recorded, and the range of possible scores is 0 - 10. Higher scores indicate less impairment. | at 14 day follow-up |