Rifabutin-Based Triple Therapy (RHB-105) for Helicobacter pylori Eradication: A Double-Blind, Randomized, Controlled Trial.

BACKGROUND: Although consensus supports eradication of Helicobacter pylori infections, antimicrobial resistance has substantially reduced eradication rates with most current therapies.

OBJECTIVE: To assess the effectiveness of a novel rifabutin-based therapy (RHB-105) for H pylori eradication.

DESIGN: Phase 3, double-blind trial (ERADICATE Hp2). (ClinicalTrials.gov: NCT03198507).

SETTING: 55 clinical research sites in the United States.

PARTICIPANTS: 455 treatment-naive adults with epigastric discomfort and confirmed H pylori infection.

INTERVENTION: RHB-105 (amoxicillin, 3 g; omeprazole, 120 mg; and rifabutin, 150 mg) versus active comparator (amoxicillin, 3 g, and omeprazole, 120 mg), given as 4 capsules every 8 hours for 14 days.

MEASUREMENTS: Between-group difference for H pylori eradication rate, demonstrated by 13 C urea breath test 4 weeks after treatment, analyzed by using the χ2 test.

RESULTS: In the intention-to-treat population, the eradication rate was higher with RHB-105 than with the active comparator (228 vs. 227 patients, respectively; 83.8% [95% CI, 78.4% to 88.0%] vs. 57.7% [95% CI, 51.2% to 64.0%]; P < 0.001). Eradication rates were unaffected by resistance to clarithromycin or metronidazole. No rifabutin resistance was detected. The most commonly reported adverse events (incidence ≥5%) were diarrhea (10.1% with RHB-105 vs. 7.9% with active comparator), headache (7.5% vs. 7.0%), and nausea (4.8% vs. 5.3%).

LIMITATION: Persons of Asian descent were excluded because of their higher prevalence of poor cytochrome P450 2C19 metabolizers.

CONCLUSION: These findings suggest potential for RHB-105 as first-line empirical H pylori therapy, addressing an unmet need in the current environment of increasing antibiotic resistance.

PRIMARY FUNDING SOURCE: RedHill Biopharma Ltd.