Rifabutin, Omeprazole, Alinia, and Doxycycline Therapy for Prior Treatment Failure Helicobacter pylori Population: A Randomized, Open-Label Clinical Pilot Study ROAD Trial

Abstract

Purpose:Helicobacter pylori infection is a global problem with a large spectrum of clinical syndromes like dyspepsia, ulcer, MALT, and gastric cancer. WHO considers Helicobacter pylori a carcinogen. Multibacterial regiments have been established to eradicate Helicobacter pylori. Treatment failure remains a clinical challenge due to microbial resistance, recrudescence, or reinfection. Bacterial genomic resistance confers a series of antimicrobials with species specificity. This study evaluates the efficacy of a novel regiment against treatment failure population. Methods: Seventy-six patients (n=76) were recruited with treatment failure with metronidazole (Mtz), clarithromycin (Cltx), amoxicillin (Amx), levofloxacin (Lvx), tetracycline (Tcx) with bismuth, in non-sequential therapy. Group A (n=36): Mtz 30/36 (83%), Amx 29/36(80%), Cltx 30/36 (83%), bismuth 23/36 (64%), Tcx 21/36 (58%), NTZ 6/36 (16%), Dox 6/36 (16%). Group B (n= 40): Mtz 31/40 (77%), Cltx 30/40 (75%), Amx 32/40 (80%), Tcx 13/40 (32%), Lvx 9/40 (22%), NTZ 9/40 (22%), Dox 9/40 (22%), bismuth 21/40 (52%). Group A received oral rifabutin 300 mg QD, alinia 500 mg BID, Dox 200 mg nightly, and omeprazole 40 mg prior to breakfast for 10 days. Group B received oral macrodantin (Mcd) 300 mg daily, Dox 200 mg nightly, alinia (Ntz) 500 mg bid, and omeprazole 40 mg for 10 days. All underwent endoscopy with four quadrant biopsies. Helicobacter pylori pre- and post-stool antigen. Group A: intestinal metaplasia (IM) 9/36 (25%), antral erosion 3/36 (8%), duodenitis 7/40 (17%). Group B: IM 11/40 (28%), duodenal ulcer 2/40 (5%), peptic ulcer 4/40 (10%). Exclusion: pregnancy, recent Clostridium difficile infection, NSAIDs, bismuth, PPI, or any antibiotics use within 2 months, gastric cancer, any hypersensitivity to study drugs, or recent chemotherapy. Results: Group A: ROAD 29/36 (72%). Stopped for itching 2/36 (8%) and 1/36 (3%) atypical chest pain. 1/36 (3%) took for 7 days. Side events in Group A: 11/36 (30%) nausea, 3/36 (8%) constipation, 4/36 (11%) headache, 2/36 (5%) diarrhea, 2/36 (5%) vomiting, 1/36 (3%) dizziness, 1/36 (3%) abdominal pain, 1/36 (3%) palpitations, and no skin rash. Group B: MOAD 21/40 (52%) eradicated. Stopped: 4/40 (10%). Side events in Group B: 13/40 (32%) nausea, 2/40 (5%) dysgeusia, 3/40 (7%) vomiting, 4/40 (10%) constipation, 2/40 (5%) diarrhea, 3/40 (7%) headache, 2/40 (5%) dizziness, 2/40 (5%) atypical chest pain, 3/40 (7%) abdominal pain, 2/40 (5%) itching, 2/40 (5%) palpitations, and no skin rash. Conclusion: Optimal eradication of Helicobacter pylori is aimed to prevent MALT or gastric cancer over time with significant morbidity and QOL. ROAD therapy has exceeded the eradication rate over MOAD in prior treatment experienced or failed therapy with symptoms. Larger trial to validate.