This was a prospective single-center an open‑label parallel blind randomized controlled trial.. This study was performed in the department of gastroenterology at Damascus hospital, Syria. We recruited appropriate candidates from patients who visited our clinic for evaluation of dyspeptic symptoms by upper gastrointestinal endoscopy between February 2020 and August 2020. Exclusion criteria were (1) younger than 18 years and older than 80 years; (2) prior eradication treatment for H pylori; (3) documented reactions to any of the studied medications ;(4) recent use of antibiotics, bismuth, or proton pump inhibitors (PPIs) in the preceding month; (5) pregnant or lactating women; (6) previous gastric surgery; (7) alcohol or opioid abuse; or (8) severe concurrent medical illnesses, such as liver failure, renal failure, or terminal malignancy. The Ethical Committee of Damascus hospital had approved the design and procedures of this research. We provide each patient with written informed consent before beginning the study procedure. We register this study as a standard randomized clinical trial (Clinicaltrial.gov, identifierNCT04348786, date:29-January-2020, https://clinicaltrials.gov/ct2/show/NCT04348786).
Eligible patients were randomized in a 1:1 ratio to receive two-week therapy of either modified bismuth quadruple (B-group) or modified concomitant levofloxacin (L-group). The B-group obtained bismuth subsalicylate 524 mg q.i.d, doxycycline 100 mg, tinidazole 500 mg, esomeprazole 20 mg each b.i.d for 14 days. While the L-group obtained levofloxacin 500 mg q.d, tinidazole 500 mg, amoxicillin 1000 mg, and esomeprazole 20 mg each b.i.d for 14 days. The indication of treatment relied on the American College of gastroenterology guideline and Maastricht V/Florence consensus report 13,15 including peptic ulcer, chronic gastritis, primary gastric MALT lymphoma, intestinal metaplasia, dyspepsia, and unexplained iron deficiency anaemia.
We used a Microsoft Excel function called (RANDBETWEEN) to generate a sequence of two randomized numbers, number one referred to the B-group, and number two referred to the L-group. We printed each code on separate paper and inserted it into sealed opaque envelopes in unchanged order, and held it in a secure locker belonging to an independent medical staff member. After obtaining informed consent, the independent medical staff member took the top envelope to assign each patient to the treatment regimen. We provided written instructions to all patients on how to take the medications. At the end of the treatment course, patients revisited the clinic to investigate side effects and evaluate compliance.
H. pylori Detection.
Eligible patients have undergone upper gastrointestinal endoscopy. Endoscopists have taken five gastric biopsies: two from the antrum, two from the body, and one from the incisura according to the Sydney system.18 Pathologists confirmed H. Pylori infection by microscopic examination after using haematoxylin, eosin, and Giemsa stains.19 We sent all biopsies to the central pathology laboratory of the same referral hospital.
At week eight, patients visited the central laboratory of our hospital and performed stool antigen tests by using the enzyme immunoassay method (EIA).20
Safety and Compliance.
Adverse drug reactions and drug regimen compliance were assessed by a qualified physician. Adverse drug reactions were evaluated using open-ended questions in patient self-reports. We reported side effects such as nausea, vomiting, diarrhoea, melena, dysgeusia, and anorexia. We evaluated compliance by counting the number of pills unused of each medication and considered that the patient was complaint if he/she has taken at least 90% of the assigned treatment protocol. Medical laboratory workers were blinded to the treatment arm. Numerical data were shown as mean, while qualitative data were expressed as a ratio.
Authors reported the results according to CONSORT.)
The primary outcome was the H pylori eradication rates of the initially assigned treatment according to intention to treat analysis (ITT), and per-protocol analysis (PPA).
Sample size and statistical analysis:
Our sample size (N = 78) was planned before the study, based on Federico et al research. the eradication rate based on ITT was 0.92 % in modified concomitant levofloxacin-containing therapy.21 We used tinidazole instead of metronidazole in the doxycycline-bismuth regimen for the first time, so we assumed that the eradication rate was 0.5, which gave us the largest sample size. 22,23 We used a power (1-β) of 99%, two tails test and Significance level(α) equal to 5%, with a 1:1 allocation ratio. Each treatment arm requires thirty-four patients.24,25 We added five patients to each group to compensate for the predicted dropout. 26,27.
Statistical tests: Chi-square test (χ2 -test) for categorical variables, and t-test for continuous data. We calculated the odds ratio with a 95% confidence interval. A P-value of less than 0.05 was considered statistically significant. We performed statistical analyses using SPSS (IBM Corp. Released in 2017. IBM SPSS Statistics for Windows, Version 25.0. Armonk, NY: IBM Corp).