RHB-105, a novel, rifabutin-based therapy, may offer a new avenue for Helicobacter pylori eradication, an industry-funded trial suggested.
Researchers conducted a phase 3, double-blind trial (ERADICATE Hp2) at 55 clinical research sites in the United States. The study enrolled 455 treatment-naive adults with epigastric discomfort and confirmed H. pylori infection. Two hundred twenty-eight participants were randomly assigned to receive RHB-105 (amoxicillin, 3 g/d; omeprazole, 120 mg/d; and rifabutin, 150 mg/d), and 227 were randomly assigned to receive an active comparator (amoxicillin, 3 g/d, and omeprazole, 120 mg/d), given as four capsules every eight hours for 14 days. Because rifabutin can cause chromaturia, all patients took 50 mg of riboflavin once daily to maintain study blinding. Patients of Asian descent were excluded because of the higher prevalence of poor metabolism of cytochrome P450 2C19. The primary efficacy end point was eradication of H. pylori, measured by 13C urea breath test at a test-of-cure visit conducted between 43 and 71 days after initiation of therapy. The study was funded by RedHill Biopharma Ltd., which was involved in study design, data collection, data analysis and interpretation, and writing and review of the manuscript. Results were published online on May 5 by Annals of Internal Medicine.
In the intention-to-treat population, the eradication rate was higher with RHB-105 than with the active comparator (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 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%). The eradication rate with RHB-105 remained high, irrespective of the resistance or susceptibility of H. pylori strains causing infection. The mean adherence to treatment was 97.5% in the RHB-105 group and 97.9% in the active comparator group.
Limitations of the study include the fact that it excluded people of Asian descent, among other limitations, the study authors noted. The findings of adherence and efficacy suggested that RHB-105 should be considered as a first-line empirical therapy for H. pylori infection, they concluded.
“In an era of increasing antimicrobial resistance, it is important to note that the efficacy of RHB-105 was not adversely affected by clarithromycin resistance or by metronidazole resistance, and there was no evidence of development of rifabutin resistance among patients who experienced treatment failure,” the authors wrote.