PALACE
Trial question
Is direct oral penicillin challenge noninferior to penicillin skin testing followed by an oral challenge in patients with a low-risk penicillin allergy?
Study design
Multi-center
Open label
RCT
Population
Characteristics of study participants
66.0% female
34.0% male
N = 377
377 patients (247 female, 130 male).
Inclusion criteria: patients with low-risk penicillin allergy with a PEN-FAST score < 3.
Key exclusion criteria: anaphylaxis associated with any drug; known history of chronic spontaneous urticaria or mast cell disease; history of non-IgE-mediated severe reactions.
Interventions
N=187 direct oral challenge (direct oral penicillin in drug challenge).
N=190 standard of care (skin prick and intradermal penicillin testing, followed by oral challenge if skin testing results are negative).
Primary outcome
Physician-verified positive immune-mediated oral penicillin challenge within 1 hour post-intervention
0.5%
0.5%
0.5 %
0.4 %
0.3 %
0.1 %
0.0 %
Direct oral
challenge
Standard of
care
Difference not exceeding
non-inferiority
margin ✓
Difference not exceeding non-inferiority margin in physician-verified positive immune-mediated oral penicillin challenge within 1 hour post-intervention (0.5% vs. 0.5%; RR 1.02, 90% CI 0.1 to 10.34).
Secondary outcomes
No significant difference in positive skin test or oral challenge (0.5% vs. 2.6%; RR 0.2, 90% CI 0.03 to 1.22).
No significant difference in positive oral challenge, per protocol (0% vs. 0.6%; ARD -0.4, 90% CI -2.6 to 1).
No significant difference in Pen-Fast 1 score (1% vs. 0.9%; AD 0.1%, 90% CI -3.1 to 3.8).
Safety outcomes
No significant differences in adverse events, immune-mediated adverse events.
Conclusion
In patients with low-risk penicillin allergy with a PEN-FAST score < 3, direct oral challenge was noninferior to standard of care with respect to a physician-verified positive immune-mediated oral penicillin challenge within 1 hour post-intervention.
Reference
Ana Maria Copaescu, Sara Vogrin, Fiona James et al. Efficacy of a Clinical Decision Rule to Enable Direct Oral Challenge in Patients With Low-Risk Penicillin Allergy: The PALACE Randomized Clinical Trial. JAMA Intern Med. 2023 Sep 1;183(9):944-952.
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