Description

Study Title:

CURE-H. Pylori: A Randomized Controlled Trial of Dexlansoprazole, Lansoprazole, and Vonoprazan with Levofloxacin-Based Triple Therapy for Helicobacter pylori Eradication

Study Background:

Helicobacter pylori (H. pylori) infection is a major global health problem, infecting approximately 44% of the population worldwide, with even higher prevalence rates in certain regions. In Pakistan, H. pylori infection affects around 60% of the population, contributing to substantial morbidity and mortality from gastric diseases, including peptic ulcer disease, gastritis, gastric cancer, and mucosa-associated lymphoid tissue lymphoma. The transmission of H. pylori is primarily fecal-oral or oral-oral, often through contaminated water or food, which is exacerbated by poor hygiene and socio-economic conditions. Infection with H. pylori is also a major risk factor for the development of gastric cancer, a leading cause of cancer-related death worldwide.

The standard treatment for H. pylori infection has traditionally been a triple therapy regimen consisting of a proton pump inhibitor (PPI), Amoxicillin, and Clarithromycin. However, the effectiveness of this regimen has decreased significantly in recent years, particularly in areas like Pakistan, where high rates of antibiotic resistance-especially to Clarithromycin and Metronidazole-are prevalent. In addition, many patients are not compliant with prescribed treatments, further decreasing the overall success rates of H. pylori eradication efforts.

Given the importance of effective treatment for H. pylori infection, there is a need for alternative regimens that can overcome resistance to standard antibiotics. Dexlansoprazole, Lansoprazole, and Vonoprazan are all PPIs, but each differs in their pharmacokinetics and mechanism of action. Dexlansoprazole has been shown to have superior pharmacokinetics, with greater maximum plasma concentration and a longer half-life compared to other PPIs. Vonoprazan, a newer PPI, has shown promise in overcoming antibiotic resistance and enhancing the efficacy of antibiotics used in H. pylori eradication. Thus, the combination of these PPIs with Levofloxacin, a broad-spectrum antibiotic, and Amoxicillin may provide an effective alternative to the standard triple therapy, especially in high-resistance regions like Pakistan.

Study Objectives:

The study aims to compare the effectiveness of Dexlansoprazole, Lansoprazole, and Vonoprazan in combination with Levofloxacin and Amoxicillin for the eradication of H. pylori. The specific objectives are:

Primary Objective:

To assess the H. pylori eradication rate in three study groups receiving either Dexlansoprazole, Lansoprazole, or Vonoprazan combined with Levofloxacin-based triple therapy, measured by Urea Breath Test (UBT) at follow-up.

Secondary Objective:

To assess the improvement in gastrointestinal symptoms post-therapy, measured using the Gastrointestinal Symptom Rating Scale (GSRS), which assesses symptoms like reflux, abdominal pain, indigestion, diarrhea, and constipation.

Study Design:

This is a three-arm, parallel-group, open-label, randomized controlled trial (RCT) designed to compare the efficacy of three different PPI-based regimens in the eradication of H. pylori. The study will be conducted over a 12-month period across several healthcare centers in Pakistan, including Peshawar, Faisalabad, Rawalpindi, Multan, Lahore, Karachi, and Quetta. The study aims to recruit a total of 942 participants, with 314 participants per arm, adjusted for a 20% dropout rate.

Methods

Study Population:

The study will include adult patients (both sexes), diagnosed with H. pylori infection via UBT, who are not currently receiving treatment for H. pylori. Patients must meet the inclusion and exclusion criteria to be eligible for the trial.

Inclusion Criteria:

Adults (≥18 years) of both sexes.

Diagnosed with H. pylori infection through UBT.

Not currently on treatment for H. pylori infection.

Exclusion Criteria:

Pregnant or lactating women.

Patients with severe mental disabilities.

Patients with a history of allergic reactions to any of the drugs used in the study.

Patients who have received antibiotics in the last two weeks before the study.

Randomization

Participants will be randomly assigned (1:1:1) to one of three treatment arms:

Arm 1: Dexlansoprazole 60mg BD + Levofloxacin 500mg OD + Amoxicillin 1g BD (for 14 days).

Arm 2: Lansoprazole 30mg BD + Levofloxacin 500mg OD + Amoxicillin 1g BD (for 14 days).

Arm 3: Vonoprazan 20mg BD + Levofloxacin 500mg OD + Amoxicillin 1g BD (for 14 days).

Randomization will ensure unbiased allocation of participants to the treatment arms.

Data Collection:

Data will be collected at two points in time:

Baseline: Prior to the initiation of treatment, demographic information, medical history, and baseline symptoms using GSRS will be collected.

Follow-up (6 weeks): At the follow-up visit, participants will undergo the UBT to assess H. pylori eradication, and their gastrointestinal symptoms will be reassessed using GSRS.

A self-reporting questionnaire will gather information on various factors, including the use of NSAIDs, previous antibiotics, alcohol consumption, smoking history, and more.

Outcome Measures:

Primary Outcome:

The H. pylori eradication rate will be measured as the percentage of participants in each arm who have a negative UBT after completing the 14-day treatment regimen.

Secondary Outcomes:

Gastrointestinal Symptom Improvement: Measured by the GSRS, which evaluates symptoms like reflux, abdominal pain, indigestion, diarrhea, and constipation.

Adverse Events: The occurrence of any side effects or adverse events related to the treatments will be monitored throughout the trial.

Statistical Analysis:

Statistical analysis will be performed using SPSS version 26. Descriptive statistics will be used to summarize the baseline characteristics of the participants. The primary outcome (H. pylori eradication rate) will be analyzed using Chi-square or Fisher's exact tests. Continuous variables, such as symptom scores, will be analyzed using t-tests or ANOVA where appropriate. An intention-to-treat analysis will be performed to include all randomized participants, regardless of adherence. A p-value \< 0.05 will be considered statistically significant.

Ethical Considerations:

The study has received approval from the Institutional Review Board (IRB) of Dow University of Health Sciences, Karachi. Participants will be fully informed about the study's purpose, procedures, risks, and benefits, and will sign an informed consent form before enrollment. The study will adhere to ethical guidelines for research involving human participants, ensuring confidentiality and voluntary participation.

Study Timeline:

Preparation Phase:

Ethical approval, participant recruitment, and site preparation (1-2 months).

Enrollment Phase:

Recruitment of 942 participants (3-4 months).

Intervention Phase:

Participants will receive the prescribed treatment for 14 days (12 months).

Follow-up Phase:

Data collection at baseline and six weeks post-treatment (12 months).

Expected Impact:

The study aims to provide valuable insights into the most effective PPI-based regimen for H. pylori eradication in regions with high antibiotic resistance, particularly in Pakistan. By comparing Dexlansoprazole, Lansoprazole, and Vonoprazan in combination with Levofloxacin and Amoxicillin, this study could lead to more effective, region-specific treatment regimens, addressing the growing challenge of antibiotic resistance. The findings will contribute to global knowledge of H. pylori treatment and may lead to new, more effective therapeutic strategies for countries with similar antibiotic resistance profiles.

The study's findings could also inform the development of patient-centered treatment plans that take into account regional resistance patterns, leading to improved patient outcomes and reduced healthcare costs. Furthermore, this research will help shape future guidelines for H. pylori management and could lead to the wider adoption of Vonoprazan and Dexlansoprazole in clinical practice.

Conclusion

This trial will provide crucial data on the comparative effectiveness of PPI-based triple therapies in H. pylori eradication. The results are expected to contribute significantly to the treatment landscape in Pakistan and other regions with similar healthcare challenges. If successful, the study could have wide-reaching implications for gastroenterology and infectious disease management, particularly in addressing the growing issue of antibiotic resistance. The evidence generated could ultimately enhance the quality of life for millions of individuals suffering from H. pylori-related diseases, while also informing public health strategies aimed at reducing the global burden of gastric cancer and other gastrointestinal disorders.