The Efficacy and Safety of Ilaprazole/Doxycycline-based Bismuth-containing Quadruple Therapy on Hp Infected Duodenal Ulcers

The Efficacy and Safety of Ilaprazole/Doxycycline-based Bismuth-containing Quadruple Therapy on Hp Infected Duodenal Ulcers: A Randomized, Parallel-controlled Multi-center Study

Helicobacter pylori (Hp) infection is one of the important causes of gastrointestinal diseases, including gastritis, peptic ulcer, and malignancies, nd the eradication of Hp can effectively cure or prevent these diseases. Now, owing to the increasingly serious antibiotic resistance, Hp eradication rate is, however, becoming decreased. In order to improve the eradication rate of Hp, clinicians pay great attention to choose more effective treatment.

Ilaprazole Enteric-Coated Tablets is a new generation of proton pump inhibitor (PPI). Previous research found that Ilaprazole had a more prolonged half-life and higher suppression of gastric acid secretion. In addition, its metabolism is not significantly influenced by CYP2C19, compared to the available PPIs. Doxycycline is in the tetracycline antibiotic class, has a stronger antibacterial force than tetracycline and its antibacterial spectrum is basically the same as tetracycline and doxycycline, so far, it is not widely used. Preliminary observations showed that Ilaprazole/Doxycycline-based quadruple therapy was effective in treating Hp infection, with less adverse reactions and good compliance with patients.

In this study, a multi-center, randomized, parallel controlled trial will be conducted in 7 hospitals in Hunan Province, China, to observe the clinical efficacy and safety of the Bismuth-containing quadruple therapy with Ilaprazole, Doxycycline, Furazolidone and Bismuth Potassium Citrate in the treatment of Hp infected duodenal ulcer. It is expected to complete 200 effective cases, including 100 cases in the experimental group and 100 cases in the control group.

Study Overview

• Status: Completed
• Conditions: Duodenal Ulcer Due to Helicobacter Pylori
• Intervention / Treatment: Drug: Doxycycline Hyclate Enteric-Coated Capsules; Drug: Ilaprazole Enteric-Coated Tablets; Drug: Furazolidone Tablets; Drug: Potassium Citrate Tablets; Drug: Amoxicillin Capsules

• Study Type: Interventional
• Enrollment (Actual): 184
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Hunan
    • Changsha, Hunan, China, 410008
      • Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410013
      • The Third Xiangya Hospital of Central South University
    • Changsha, Hunan, China, 410011
      • The Second Xiangya Hospital of Central South University
    • Hengyang, Hunan, China, 421001
      • The First Affiliated Hospital of University of South China
    • Loudi, Hunan, China, 417000
      • Loudi Central Hospital
    • Shaoyang, Hunan, China, 422000
      • Shaoyang Central Hospital
    • Yongzhou, Hunan, China, 425000
      • The Affiliated Hospital Of YongZhou Vocational Technical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 63 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Has endoscopic evidence of active duodenal ulcer(within a week before participate), accompanying or not accompanied with abdominal pain/abdominal discomfort, acid, heartburn, abdominal distention, belching and other corresponding symptoms.
2. The diameter of the ulcer is 0.3 to 2.0cm, and the number is less than or equal 2.
3. Has evidence(s) of Hp infection. (13C-UBT/14C-UBT/Pathological test)
4. Has a history of antiacid medication, but has been stopped for more than 2 weeks.
5. Has not used antibiotics and (or) bismuth agents in nearly four weeks.
6. Understand and be willing to participate in this clinical trial.

Exclusion Criteria:

1. Has been taking ulcer medications, such as non-steroidal anti-inflammatory drugs, adrenal corticosteroids etc.
2. Has allergic and idiosyncratic responses to the tested drugs and (or) control drugs.
3. Has a diagnosis of duodenal carcinelcosis or a duodenal ulcer can not rule out the the possibility of malignancy (patients with gastrointestinal mucosal epithelial mild atypical hyperplasia are not ruled out) or compound ulcers.
4. Has severe or progressive dysphagia, weight loss, gastrointestinal bleeding or other alarm symptoms.
5. Has esophageal or gastric varices, Zollinger-Ellison syndrome, or serious complications such as pyloric obstruction, active bleeding in the endoscope; esophageal erosion or ulcers, other digestive serious diseases, Such as Crohn's disease, ulcerative colitis.
6. Has a history of gastric acid suppression surgery, esophageal surgery, or digestive organ surgery, with the exception of simple suture of perforation.
7. Is pregnant, breastfeeding or has a family planning during whole trail.
8. Has serious cardiovascular, pulmonary, hepatic, renal, hematological or endocrine disease with uncontrolled condition.
9. Has participated in other clinical trials within 3 months prior to the trial.
10. Is required to use the prescribed anti-ulcer drug during the trial.
11. Has a history of drug and (or) alcohol abuse.
12. Has restriction on sodium, with metabolic alkalosis and (or) hypocalcemia.
13. Has a long-term use of clopidogrel.
14. Has other reasons for not to participating in clinical trials.

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 1; week1 to week2：Doxycycline Hyclate Enteric-Coated Capsules 0.1g,orally,twice daily,taken with meals, Ilaprazole Enteric-Coated Tablets 5mg,orally,twice daily, Furazolidone Tablets 0.1g,orally,twice daily,taken with meals, Bismuth Potassium Citrate Tablets 220mg,orally,twice daily week3 to week4：Ilaprazole Enteric-Coated Tablets 5mg,orally,once daily	Drug: Doxycycline Hyclate Enteric-Coated Capsules; group 1,0.1g*10 capsules/box, produced by Yung Shin Pharm.Ind.(Kunshan) Co.,Ltd.; Drug: Ilaprazole Enteric-Coated Tablets; group 1 and group 2,5mg*6 capsules/box, produced by Livzon Pharmaceutical Group Inc; Drug: Furazolidone Tablets; group 1 and group 2,0.1g*100 tablets/bottle,produced by Shanxi Yunpeng Pharmaceutical co.,Ltd.; Drug: Potassium Citrate Tablets; group 1 and group 2,110mg*40 tablets/bottle,produced by Livzon Pharmaceutical Group Inc
Active Comparator: group 2; Amoxicillin Capsules 1g,orally,twice daily,taken with meals, Ilaprazole Enteric-Coated Tablets 5mg,orally,twice daily, Furazolidone Tablets 0.1g,orally,twice daily,taken with meals, Bismuth Potassium Citrate Tablets 220mg,orally,twice daily. week3 to week4：Ilaprazole Enteric-Coated Tablets 5mg,orally,once daily	Drug: Ilaprazole Enteric-Coated Tablets; group 1 and group 2,5mg*6 capsules/box, produced by Livzon Pharmaceutical Group Inc; Drug: Furazolidone Tablets; group 1 and group 2,0.1g*100 tablets/bottle,produced by Shanxi Yunpeng Pharmaceutical co.,Ltd.; Drug: Potassium Citrate Tablets; group 1 and group 2,110mg*40 tablets/bottle,produced by Livzon Pharmaceutical Group Inc; Drug: Amoxicillin Capsules; group 2,0.5g*24 capsules/box, produced by United Laboratories（Zhuhai）

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The eradication rate of H. pylori infection	Evaluated by 13C-urea breath test (13C-UBT), 14C-urea breath test (14C-UBT), or Pathological examination.	Visit period 3 (After day 56)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The healing rate of duodenal ulcer(s)	Duodenal ulcer healing rate is defined as the percentage of participants with complete healing of ulcer (according to Sakita-Fukutomi classification) under endoscope.	Visit period 2 (day 28±1)
Number of duodenal ulcer(s)	Confirmed by endoscope.	Visit period 2 (day 28±1)
Maximum diameter of duodenal ulcer(s)	Confirmed by endoscope (cm).	Visit period 2 (day 28±1)
Surrounding inflammation and(or) erosion of duodenal ulcer(s)	Confirmed by endoscope.	Visit period 2 (day 28±1)
Incidence of bleeding	Confirmed by endoscope.	Visit period 2 (day 28±1)
Improvement of gastric symptoms	Improvement is defined as the total change from baseline symptoms scores of Symptom Rating Scale(Includidng 9 items: Pain in day, Pain in night, Burning in day, Burning in night, Acid reflux in day, Acid reflux in night, Nausea and vomiting, Belching, Abdominal distension. Depending on severity and frequency, scale ranges from 0-3 points.).	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Degree of pain	Evaluated by clinical symptoms scores; Pain in day 0 point: No pain. 1 point: Mild pain, do not affect daily life and work, do not have to take medicines. 2 points: Obvious pain,partly affect daily life and work, or have to take medicines. 3 points: Severe pain, must rest, taking medicine is ineffective; Pain in night 0 point: No pain. 1 point: Mild pain, do not affect daily life and work, do not have to take medicines. 2 points: Obvious pain,partly affect daily life and work, or have to take medicines. 3 points: Severe pain, must rest, taking medicine or eat is ineffective	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Degree of burning	Evaluated by clinical symptoms scores; Burning in day 0 point: No burning. 1 point: Occasionally. 2 points: Frequently and duration prolonged. 3 points: Continuously, use antacid to alleviate briefly.; Burning in night 0 point: No burning. 1 point: Occasionally. 2 points: Frequently and duration prolonged. 3 points: Continuously, use antacid to alleviate briefly.	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Degree of acid reflux	Evaluated by clinical symptoms scores; Acid reflux in day 0 point: No acid reflux. 1 point: Occasionally. 2 points: One to two times a day. 3 points: Several times a day.; Acid reflux in night 0 point: No acid reflux. 1 point: Occasionally. 2 points: One to two times a day. 3 points: Several times a day.	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Degree of nausea and vomiting	Evaluated by clinical symptoms scores Nausea and vomiting 0 point: No nausea. 1 point: Occasionally and briefly. 2 points: Frequent nausea, vomiting. 3 points: Continuous nausea, frequent vomiting.	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Degree of belching	Evaluated by clinical symptoms scores Belching 0 point: No belching. 1 point: Occasionally. 2 points: Frequently. 3 points: Continuously, and affect normal activities.	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Degree of abdominal distension	Evaluated by clinical symptoms scores Abdominal distension 0 point: No abdominal distension. 1 point: Occasionally. 2 points: Obvious abdominal distension. 3 points: Severe abdominal distension, and affect normal activities.	Screening period (day -3~0), Visit period 1 (day 14±1), Visit period 2 (day 28±1)
Symptom disappearance time		Visit period 1 (day 14±1), Visit period 2 (day 28±1)

Collaborators and Investigators

• Sponsor: The Third Xiangya Hospital of Central South University
• Collaborators: Livzon Pharmaceutical Group Inc.; Yung Shin Pharm. Ind. Co., Ltd.
• Investigators: Principal Investigator: JINGSHU CHI, The Third Xiangya Hospital of Central South University; Principal Investigator: XIAOMING LIU, The Third Xiangya Hospital of Central South University

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2017
• Primary Completion (Actual): June 20, 2019
• Study Completion (Actual): September 20, 2019

Study Registration Dates

• First Submitted: October 30, 2017
• First Submitted That Met QC Criteria: November 9, 2017
• First Posted (Actual): November 17, 2017

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 26, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: Helicobacter pylori eradication; Duodenal Ulcer; Ilaprazole/Doxycycline-based Bismuth-containing quadruple therapy
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Stomach Diseases; Intestinal Diseases; Peptic Ulcer; Duodenal Diseases; Ulcer; Duodenal Ulcer; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents, Local; Anti-Infective Agents; Enzyme Inhibitors; Natriuretic Agents; Anti-Bacterial Agents; Diuretics; Respiratory System Agents; Antiprotozoal Agents; Antiparasitic Agents; Monoamine Oxidase Inhibitors; Antimalarials; Expectorants; Anti-Infective Agents, Urinary; Renal Agents; Antitrichomonal Agents; Doxycycline; Amoxicillin; Potassium Citrate; Furazolidone
• Other Study ID Numbers: xucanxia2000

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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