Background and Purpose: 

• ~10% of all US patients report a penicillin allergy, however, estimates suggest that less than 5% of those labeled with a penicillin allergy are truly allergic 
• Because the standard skin testing for penicillin allergy is resource-intensive, the Copaescu et. Al (JAMA Int Med 2023) designed a clinical trial to determine whether oral challenge with penicillin is noninferior to the standard of care of penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy 

Methods: 

• Design and Participants  
  • Parallel, 2-arm, noninferiority, open-label, multicenter randomized clinical trial  
  • 6 specialized centers in the US, Canada, and Australia 
  • Eligible adults had a PEN-FAST score lower than 3 
    • PEN-FAST is an internationally validated clinical decision rule that enables point-of-care risk assessment for adults reporting penicillin allergies 
• Randomization 
  • Patients were randomly assigned to either the control group (penicillin skin test) or to the intervention group (direct oral challenge) 
• Primary Outcome and Measure 
  • Physician-verified positive immune-mediated oral penicillin challenge within 1-hour post-intervention in the intention-to-treat population 

Results: 

• 377 patients (65.5% female) with a median age of 51 years were included in the analysis  
  • 187 patients in the intervention group and 190 patients in the control group 
• The primary outcome occurred in one patient in both groups. 
• No serious adverse events occurred in either group. 

Conclusions: 

• Direct oral penicillin challenge in patients with a low-risk penicillin allergy was noninferior compared with standard-of-care skin testing followed by oral challenge. 
• The authors state: 

Direct oral penicillin challenge is a safe procedure to help remove more penicillin allergy labels in patients with a low-risk history compared to the standard-of-care penicillin skin tests alone. 

Learn More – Primary Sources: 

JAMA The PALACE RCT