Clinical trial NCT01864200: Randomized, Double-Blind, Placebo-Controlled Study: CroFab® vs Placebo for Copperhead Snake Envenomation
Official title: A Randomized, Double-Blind, Placebo-Controlled Study Comparing CroFab® vs Placebo With Rescue Treatment for Copperhead Snake Envenomation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Snake Bites
Lead sponsor: BTG International Inc.
Sponsor class: OTHER
First posted: 2013-05-29
Enrollment: 74
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Patient Specific Functional Scale Score
timeFrame: at 14 day follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Georgia Regents University
state: Georgia
city: Kansas City
country: United States
facility: University of Kansas Hospital
state: Kansas
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Greenville
country: United States
facility: Vidant Medical Center
state: North Carolina
city: Allentown
country: United States
facility: Lehigh Valley Hospital Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Columbia
country: United States
facility: Palmetto Health Richland
state: South Carolina
city: Bryan
country: United States
facility: St Joseph Regional Health Center
state: Texas
city: Dallas
country: United States
facility: University of Texas - Southwestern
state: Texas
city: Houston
country: United States
facility: Ben Taub General Hospital
state: Texas
city: Houston
country: United States
facility: Texas Children's Hospital
state: Texas
city: Temple
country: United States
facility: Scott & White Hospital
state: Texas
city: Charlottesville
country: United States
facility: University of Virginia
state: Virginia
city: Richmond
country: United States
facility: Virginia Commonwealth University
state: Virginia
city: Huntington
country: United States
facility: Marshall Health
state: West Virginia
Study officials:
affiliation: BTG International Inc.
name: Maria Gasior, MD
role: PRINCIPAL_INVESTIGATOR
References: