NEJM evidence · 2026
Feasibility Trial of Prolonged versus Single-Dose Challenge in Penicillin Allergy.
СтатьяРандомизированное исследованиеМногоцентровое исследованиеНазвание и аннотация: Перевод в очереди
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Rose Morgan, Vogrin Sara, Mitri Elise A, De Luca Joseph, Lapirow Daniel, Reynolds Gemma K, Hall Rebecca, McInnes Kerryn, James Fiona, Ng Irvin, Sullivan Richard, Lane Michael, Legg Amy, Copaescu Ana, Goh Michelle S, Chua Kyra Y L, Holmes Natasha E, Trubiano Jason A
Аннотация
BACKGROUND: We aimed to evaluate the feasibility of conducting a multicenter, double-blind, placebo-controlled trial of prolonged (i.e., multidose) compared with single-dose amoxicillin challenge in patients with a history of delayed penicillin allergy and to assess the frequency of immune-mediated adverse events.
METHODS: We conducted a parallel, double-blind, placebo-controlled multicenter randomized feasibility trial at four Australian hospitals. Adults who had a history of penicillin allergy of delayed-onset (2 or more hours after exposure) or unknown timing and had tolerated a single-dose oral challenge to amoxicillin were eligible to enroll. Participants were randomly assigned 1:1 using a permuted block design to either a 5-day amoxicillin challenge (intervention) or a placebo (control). The primary outcome measures were adherence to the intervention (N, % taking at least 80% of capsules), need for unblinding (N, %), and recruitment feasibility (N, % of eligible patients enrolled). The secondary outcome measures included positive oral challenges, defined as immune-mediated adverse events up to and including day 7.
RESULTS: We screened 302 adults and randomly assigned 120 participants to intervention (n=60) or control (n=60). The mean (standard deviation) age was 49.4 years (17.6). Allergy histories included 42% (50/120) delayed reactions and 58% (70/120) of unknown timing. Adherence to the intervention was 83% (100/120; 95% confidence interval, 75 to 90) (88% intervention and 78% control). No patients were unblinded and recruitment feasibility was 71% (120/169). The number of positive oral challenges was 7 of 60 (12%) in the intervention group and 3 of 60 (5%) in the control group (risk difference, 6.7 percentage points; 95% confidence interval, -3.2 to 16.5). One serious adverse event (1/60, 1.7%, severe cutaneous adverse reaction) was observed in the control group.
CONCLUSIONS: Conducting a double-blind, placebo-controlled randomized trial of single-dose versus multidose oral amoxicillin challenge was feasible. A fully powered efficacy trial is needed to assess between-group differences in immune-mediated adverse events. (Funded by Austin Health and others; trial registration: ANZCTR - ACTRN12623001242617, registered on November 30, 2023.).
METHODS: We conducted a parallel, double-blind, placebo-controlled multicenter randomized feasibility trial at four Australian hospitals. Adults who had a history of penicillin allergy of delayed-onset (2 or more hours after exposure) or unknown timing and had tolerated a single-dose oral challenge to amoxicillin were eligible to enroll. Participants were randomly assigned 1:1 using a permuted block design to either a 5-day amoxicillin challenge (intervention) or a placebo (control). The primary outcome measures were adherence to the intervention (N, % taking at least 80% of capsules), need for unblinding (N, %), and recruitment feasibility (N, % of eligible patients enrolled). The secondary outcome measures included positive oral challenges, defined as immune-mediated adverse events up to and including day 7.
RESULTS: We screened 302 adults and randomly assigned 120 participants to intervention (n=60) or control (n=60). The mean (standard deviation) age was 49.4 years (17.6). Allergy histories included 42% (50/120) delayed reactions and 58% (70/120) of unknown timing. Adherence to the intervention was 83% (100/120; 95% confidence interval, 75 to 90) (88% intervention and 78% control). No patients were unblinded and recruitment feasibility was 71% (120/169). The number of positive oral challenges was 7 of 60 (12%) in the intervention group and 3 of 60 (5%) in the control group (risk difference, 6.7 percentage points; 95% confidence interval, -3.2 to 16.5). One serious adverse event (1/60, 1.7%, severe cutaneous adverse reaction) was observed in the control group.
CONCLUSIONS: Conducting a double-blind, placebo-controlled randomized trial of single-dose versus multidose oral amoxicillin challenge was feasible. A fully powered efficacy trial is needed to assess between-group differences in immune-mediated adverse events. (Funded by Austin Health and others; trial registration: ANZCTR - ACTRN12623001242617, registered on November 30, 2023.).