Accuracy and Agreement of a 45 mg Versus a 75 mg 13C-Urea Breath Test for the Diagnosis of Helicobacter pylori Infection in Adults: A Randomized Crossover Trial

Background: The optimal 13C-urea breath test (UBT) dosage for diagnosing Helicobacter pylori remains debated. We compared the accuracy and agreement of a low-dose 45 mg tablet (without citric acid) versus the standard 75 mg granule (with citric acid) protocol. Methods: In this prospective, randomized crossover trial, adults underwent both a 45 mg and a 75 mg 13C-UBT on the same day. Breath samples were collected at 15 and 30 min. The primary outcome was diagnostic agreement at 30 min. Secondary outcomes included diagnostic performance against a composite reference standard, wherein concordant 45 mg and 75 mg UBT results were presumed to represent true H. pylori status, while discordant cases underwent endoscopic reference testing (rapid urease test and histology, with immunohistochemistry where required), stratified by age and BMI. Results: For the 431 participants included, the 45 mg and 75 mg tests showed substantial agreement at 30 min (90.3%; κ = 0.766). The 30 min sampling time yielded significantly better accuracy than 15 min for both doses. The 45 mg protocol achieved excellent accuracy (AUC 0.953), statistically non-inferior to the 75 mg protocol (AUC 0.966; p = 0.50). Notably, in participants aged <40 years or with BMI < 25.0 kg/m2, the 45 mg protocol demonstrated robust performance (AUC 0.977 and 0.966, respectively), comparable to the 75 mg standard (p > 0.05). No adverse events occurred. Conclusions: The low-dose 45 mg 13C-UBT provides high diagnostic agreement and comparable clinical performance to the standard 75 mg protocol without requiring citric acid acidification. Its robust performance in younger, lower-BMI individuals shows clinical promise. However, because diagnostic accuracy analyses partly relied on a composite reference assumption, further externally validated studies are required before broad screening-policy claims can be made.