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

Snake Bites Clinical Trial

— Copperhead  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01864200
• Other study ID #: BTG-PR005-002
• Status: Completed
• Phase: Phase 4
• First received: May 24, 2013
• Last updated: October 19, 2017
• Start date: July 2013
• Est. completion date: December 2015

Study information

• Verified date: October 2017
• Source: BTG International Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 74
• Est. completion date: December 2015
• Est. primary completion date: December 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Years and older

Eligibility

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)

1. Lower extremity: swelling crossing hip joint

2. 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

Related Conditions & MeSH terms

• Snake Bites

Intervention

Biological:
• Crotalidae polyvalent immune fab (ovine)
crotalidae antivenom
• Placebo
Saline placebo

Locations

Country	Name	City	State
United States	Lehigh Valley Hospital Center	Allentown	Pennsylvania
United States	Georgia Regents University	Augusta	Georgia
United States	St Joseph Regional Health Center	Bryan	Texas
United States	University of North Carolina	Chapel Hill	North Carolina
United States	Medical University of South Carolina	Charleston	South Carolina
United States	University of Virginia	Charlottesville	Virginia
United States	Palmetto Health Richland	Columbia	South Carolina
United States	University of Texas - Southwestern	Dallas	Texas
United States	Duke University	Durham	North Carolina
United States	Vidant Medical Center	Greenville	North Carolina
United States	Ben Taub General Hospital	Houston	Texas
United States	Texas Children's Hospital	Houston	Texas
United States	Marshall Health	Huntington	West Virginia
United States	University of Kansas Hospital	Kansas City	Kansas
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	Virginia Commonwealth University	Richmond	Virginia
United States	Washington University	Saint Louis	Missouri
United States	Scott & White Hospital	Temple	Texas

Sponsors (1)

Lead Sponsor	Collaborator
BTG International Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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