Prolonged versus single dose in penicillin oral challenge testing: protocols for a pilot and definitive randomised...

Area of Science:

• Clinical Medicine
• Allergy and Immunology
• Pharmacology

Background:

• Penicillin allergy labels (PALs) affect 10% of hospitalized patients globally, leading to poorer outcomes.
• Most PALs are inaccurate and should be removed to improve patient care.
• Oral penicillin challenge is effective for PAL removal, but optimal duration is unclear.

Purpose of the Study:

• To assess the feasibility and safety of a prolonged (5-day) oral penicillin challenge versus a single-dose challenge.
• To determine if a 5-day challenge is superior to a single-dose challenge in excluding delayed penicillin allergy reactions.
• To establish the foundation for a definitive trial (PROSPECTOR-2) on prolonged penicillin challenge efficacy.

Main Methods:

• Two parallel, double-blind, placebo-controlled trials (PROSPECTOR-1 and PROSPECTOR-2) were designed.
• Patients with delayed or unknown penicillin allergy history, who passed an initial challenge, were recruited.
• PROSPECTOR-1 assessed feasibility of single-dose vs. 5-day challenge; PROSPECTOR-2 will assess superiority.

Main Results:

• PROSPECTOR-1 will evaluate the safety and feasibility of both challenge durations.
• PROSPECTOR-2, using a vanguard design, will compare the 5-day challenge against the single-dose challenge.
• Data from each trial will be analyzed separately, with sample size adjustments for PROSPECTOR-2 based on PROSPECTOR-1 findings.

Conclusions:

• The PROSPECTOR studies aim to resolve the optimal duration for oral penicillin challenge.
• Findings will inform clinical practice regarding the removal of inaccurate penicillin allergy labels.
• This research is crucial for improving antibiotic stewardship and patient safety.