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

Study Overview
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Brief Summary
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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.

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

Conditions
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Duodenal Ulcer Due to Helicobacter Pylori

Intervention / Treatment
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* Drug: Doxycycline Hyclate Enteric-Coated Capsules
* Drug: Amoxicillin Capsules
* Drug: Ilaprazole Enteric-Coated Tablets
* Drug: Furazolidone Tablets
* Drug: Potassium Citrate Tablets


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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. The diameter of the ulcer is 0.3 to 2.0cm, and the number is less than or equal 2. Has evidence(s) of Hp infection. (13C-UBT/14C-UBT/Pathological test) Has a history of antiacid medication, but has been stopped for more than 2 weeks. Has not used antibiotics and (or) bismuth agents in nearly four weeks. Understand and be willing to participate in this clinical trial. Exclusion Criteria: Has been taking ulcer medications, such as non-steroidal anti-inflammatory drugs, adrenal corticosteroids etc. Has allergic and idiosyncratic responses to the tested drugs and (or) control drugs. 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. Has severe or progressive dysphagia, weight loss, gastrointestinal bleeding or other alarm symptoms. 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. Has a history of gastric acid suppression surgery, esophageal surgery, or digestive organ surgery, with the exception of simple suture of perforation. Is pregnant, breastfeeding or has a family planning during whole trail. Has serious cardiovascular, pulmonary, hepatic, renal, hematological or endocrine disease with uncontrolled condition. Has participated in other clinical trials within 3 months prior to the trial. Is required to use the prescribed anti-ulcer drug during the trial. Has a history of drug and (or) alcohol abuse. Has restriction on sodium, with metabolic alkalosis and (or) hypocalcemia. Has a long-term use of clopidogrel. Has other reasons for not to participating in clinical trials.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group 1<br>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<br>* group 1,0.1g*10 capsules/box, produced by Yung Shin Pharm.Ind.(Kunshan) Co.,Ltd.<br>Drug: Ilaprazole Enteric-Coated Tablets<br>* group 1 and group 2,5mg*6 capsules/box, produced by Livzon Pharmaceutical Group Inc<br>Drug: Furazolidone Tablets<br>* group 1 and group 2,0.1g*100 tablets/bottle,produced by Shanxi Yunpeng Pharmaceutical co.,Ltd.<br>Drug: Potassium Citrate Tablets<br>* group 1 and group 2,110mg*40 tablets/bottle,produced by Livzon Pharmaceutical Group Inc<br>|
| Active Comparator: group 2<br>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: Amoxicillin Capsules<br>* group 2,0.5g*24 capsules/box, produced by United Laboratories（Zhuhai）<br>Drug: Ilaprazole Enteric-Coated Tablets<br>* group 1 and group 2,5mg*6 capsules/box, produced by Livzon Pharmaceutical Group Inc<br>Drug: Furazolidone Tablets<br>* group 1 and group 2,0.1g*100 tablets/bottle,produced by Shanxi Yunpeng Pharmaceutical co.,Ltd.<br>Drug: Potassium Citrate Tablets<br>* group 1 and group 2,110mg*40 tablets/bottle,produced by Livzon Pharmaceutical Group Inc<br>|

What is the study measuring?
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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) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Helicobacter pylori eradication, Duodenal Ulcer, Ilaprazole/Doxycycline-based Bismuth-containing quadruple therapy