ILTHPI - Comparison of Medicament Containing Tetracycline, Metronidazole, Bismuth Versus Amoxicillin, Metronidazole, Clarithromycin

Visiting Staff, Division of Gastroenterology and Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

Helicobacter pylori (H. pylori) is a spiral shaped, microaerophilic, gram negative bacterium. The organism resides in the acid and mucous layer of the human gastric mucosa, adheres to and colonizes the mucosal surface of the stomach and the mucosal epithelium with gastric metaplasia of duodenal bulb. Many studies have shown that H. pylori is an important causal factor of chronic gastritis, peptic ulcer disease, gastric cancer and gastric lymphoma. Endoscopic examination is indicated to confirm the above diagnosis for patient with H. pylori infection. The eradication rate of standard triple therapy has fallen below 80% in many countries due to the worldwide increasing prevalence of antibiotic resistant strains. This is related to the special gastric milieu of H. pylori, which leads to a more difficult and complicated treatment for achieving a successful eradication rate than other bacteria. Several strategies have been proposed to increase the eradication rate in the first line therapy or as a rescue therapy. However, these rescue therapies will increase the side effects and costs of treatment, decrease the compliance of patients and increase the rate of worldwide antibiotic resistance steadily. The WHO has listed H. Pylori as one of 12 antibiotic-resistant bacteria that have the greatest threat to human health in Feb. 2017. Our previous studies suggested that the administration of single -dose therapeutic agents can achieve the eradication of H. pylori immediately while conducting the endoscopic examination. The eradication rate of intraluminal therapy for H. pylori infection (ILTHPI) is 53.7% (51/95), and control the intragastric pH above 4 prior to the ILTHPI can even reach a 72.0%(36/50) eradication rate of H. pylori.

According to the recent Taiwan consensus for the treatment of H. pylori in 2017, the first line therapeutic regiment of H. pylori containing Amoxicillin, Clarithromycin, and Metronidazole if the rate of Clarithromycin resistance is below 15%, while the first line therapeutic regiment of H. pylori containing tetracycline, metronidazole, and bismuth subcitrate if the rate of Clarithromycin resistance is above 15%. We aimed to evaluate and compare the efficacy of medicament containing Tetracycline, Metronidazole, and Bismuth versus Amoxicillin, Metronidazole, and Clarithromycin for the Intraluminal therapy of Helicobacter pylori infection.

Study Overview

• Status: Completed
• Conditions: Helicobacter Pylori Infection
• Intervention / Treatment: Drug: Tetracycline, Metronidazole, Bismuth subcitrate; Drug: Amoxicillin, Metronidazole, Clarithromycin

Detailed Description

During the endoscopic examination, patient is sedated with intravenous Midazolam 5mg and Fentanyl 0.05mg, the vital signs will be closely monitored by physiological monitor (PHILIPS SureSigns VM6). The treatment will be terminated immediately if unstable vital sign detected or if patient asks for termination. The pH value of gastric juice will be measured with the pH test strips. and the he gastric mucus is irrigated with acetylcysteine solution. The investigators randomly assigned medicaments containing different antibiotic powders either Tetracycline 2g, Metronidazole 2g, and Bismuth 480mg (Group A) or Amoxicillin 3g, Metronidazole 2g, and Clarithromycin 1g (Group B) to dispense on the surface of gastric mucosa and duodenal mucosa of duodenal bulb. After the intraluminal therapy, patients will rest for 30 to 60 minutes and go home if the effect of sedation subsided. Patients can take meal if no abdominal discomfort. C13-Urea breath test (UBT) will be used to assess the existence of H. pylori 2 weeks after the intraluminal therapy. Patients failed to achieve intraluminal eradication of H. pylori will be assigned to 7-day concomitant therapy (Group A) or 7-day bismuth quadruple therapy (Group B). The C13-UBT will be used to assess the existence of H. pylori 4 weeks after the oral antibiotic therapy. The overall eradication rates of the intraluminal therapy plus the oral antibiotics therapies will be evaluated.

• Study Type: Interventional
• Enrollment (Actual): 104
• Phase: Phase 4

Contacts and Locations

Study Locations

• Taiwan
  • Taipei, Taiwan, 10449
    • Division of Gastroenterology and Department of Internal Medicine, Mackay Memorial Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients aged between 20 years and 75 years
2. Patients have H. pylori infection and have not treated with oral antibiotics
3. Patients are willing to receive the intraluminal therapy. The written informed consents will be obtained from all patients prior to enrollment.

Exclusion Criteria:

• Patients will be excluded from the study if any one of the following criteria is present:

  1. Children and teenagers aged less than 20 years, or adult greater than 75 years
  2. Contraindication for endoscopic examination or food retention in the gastric lumen
  3. History of gastrectomy; Gastroduodenal stenosis、deformity or obstruction; Gastroduodenal malignancy, including adenocarcinoma and lymphoma
  4. Contraindication to treatment drugs: previous allergic reaction to antibiotics of study, PPI (Lansoprazole), Acetylcysteine and Sucralfate; pregnant or lactating women
  5. Severe concurrent acute or chronic illness: renal failure, decompensated cirrhosis of liver, incurable malignant disease
  6. Patients who cannot give informed consent by himself or herself

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A (Tetracycline, Metronidazole, and Bismuth); Intraluminal Therapy for Helicobacter pylori Infection - Single dose medicament containing Tetracycline 2g, Metronidazole 2g, and Bismuth subcitrate 480 mg	Drug: Tetracycline, Metronidazole, Bismuth subcitrate; 52 participants (Group A) are randomly assigned to receive intraluminal eradication of H. pylori with medicament containing Tetracycline, Metronidazole, and Bismuth subcitrate; Other Names: Bismuth Trioxide
Active Comparator: Group B (Amoxicillin, Metronidazole, and Clarithromycin); Intraluminal Therapy for Helicobacter pylori Infection - Single dose medicament containing Amoxicillin 3g, Metronidazole 2g, and Clarithromycin 1g	Drug: Amoxicillin, Metronidazole, Clarithromycin; 52 participants (Group B) are randomly assigned to receive intraluminal eradication of H. pylori with medicament containing Amoxicillin, Metronidazole, and Clarithromycin; Other Names: Klaricid

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The eradication rates of intraluminal therapy	To evaluate and compare the eradication rates of different medicaments for the Intraluminal Therapy for Helicobacter pylori Infection between Group A and Group B.	C13-UBT will be used to assess the existence of H. pylori 2 weeks after the intraluminal therapy

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The adverse events of intraluminal therapy	of different medicaments for the Intraluminal Therapy for Helicobacter pylori Infection between Group A and Group B.	Within one week after the Intraluminal Therapy for Helicobacter pylori Infection
The eradication rates of oral antibiotic rescue therapies	To evaluate and compare the eradication rates of different oral antibiotic rescue therapies for failed Intraluminal Therapy between concomitant therapy ( Group A) and bismuth-based quadruple therapy (Group B)	C13-UBT will be used to assess the existence of H. pylori 4 weeks after the oral antibiotics rescue therapy
The adverse events of oral antibiotic rescue therapies	To evaluate and compare the adverse events of different oral antibiotic rescue therapies for failed Intraluminal Therapy between concomitant therapy ( Group A) and bismuth-based quadruple therapy (Group B)	Within one week after complete the oral antibiotics rescue therapy

Collaborators and Investigators

• Sponsor: Mackay Memorial Hospital
• Investigators: Principal Investigator: Tai-cherng Liou, MD, Division of Gastroenterology and Department of Internal Medicine, Mackay Memorial Hospital

Study record dates

Study Major Dates

• Study Start (Actual): April 19, 2021
• Primary Completion (Actual): August 30, 2022
• Study Completion (Actual): December 16, 2022

Study Registration Dates

• First Submitted: April 14, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 21, 2021

Study Record Updates

• Last Update Posted (Actual): January 4, 2023
• Last Update Submitted That Met QC Criteria: January 1, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Metronidazole; Clarithromycin; Amoxicillin; Helicobacter Pylori; Proton pump inhibitor; Tetracycline; Bismuth
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Gastrointestinal Agents; Anti-Bacterial Agents; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Protein Synthesis Inhibitors; Antiprotozoal Agents; Antiparasitic Agents; Anti-Ulcer Agents; Antacids; Metronidazole; Amoxicillin; Clarithromycin; Bismuth; Tetracycline; Bismuth tripotassium dicitrate
• Other Study ID Numbers: 21MMHIS016e

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No