H. Pylori Eradication for Moderate ITP

Study Overview
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Brief Summary
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The purpose of this study is to determine the efficacy of H. pylori eradication for the treatment of chronic or persistent immune thrombocytopenic purpura (ITP) patients with moderate thrombocytopenia. This is a multi-center, open label, prospective randomized phase IIl study.

Detailed Description
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Current treatment guideline of ITP recommends corticosteroid as the first line treatment when patient has active bleeding or less than 30×10^9/L of platelet, because of side effect and cost issues. Since the first case report by Italian study, several investigators have reported that secondary immune thrombocytopenia (ITP) can occur in patients with Helicobacter pylori (H. pylori) infection. We already reported the efficacy of H. pylori eradication in moderate ITP patients with phase II study (Annals Hematology 2015:94:739-46). To improve the evidence of this strategy for the treatment of moderate ITP, we plan to start this multi-center, open label, prospective randomized phase 3 study.

Official Title
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Efficacy of Helicobacter Pylori Eradication for the Treatment of Chronic or Persistent Immune Thrombocytopenic Purpura Patients With Moderate Thrombocytopenia: Multicenter Prospective Randomized Phase 3 Study

Conditions
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Immune Thrombocytopenic Purpura, Helicobacter Pylori, Immune Thrombocytopenia

Intervention / Treatment
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* Drug: treatment : H. pylori eradication


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 19 years Persistent or chronic ITP patients defined by international working group 30 X 10^9/L ≤ platelet level ≤ 80 X 10^9/L H. pylori infection should be confirmed by at least one of tests: urea breath test (UBT), CLO, stool H. pylori Ag, H. pylori in gastric tissue (reported by a trained pathologist) No history of any ITP treatment for the past 3 months No previous history of H. pylori eradication treatment Patients who voluntarily participate in this study and with informed consents Exclusion Criteria: patients who have any cause of thrombocytopenia such as HIV, HCV infection, lymphoproliferative disease, malignant neoplasm, liver disease, definite SLE and other autoimmune diseases, drugs, MDS and leukemia uncontrolled hypothyroidism or hyperthyroidism active bleeding for the past 3 months or history of hemorrhagic gastric ulcer or brain hemorrhage active infection patients who are taking anticoagulant or aspirin patients with penicillin allergy or side effects of macrolide patients who are taking mizolastine, terfenadine, cisapride, pimozide, astemizole, ergot alkaloid and its derivatives (ergotamine and dihydroergotamine), bepridil or atazanavir patients who have known allergy or severe side effect on study drugs pregnant or lactating women

Ages Eligible for Study
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Minimum Age: 19 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
Interventional Model Description: treatment group vs control group Patients in treatment group will be treated with antibiotics for H. pylori eradication at visit 1. Control group has 2 stage. Fot the 1st stage (for 3 months), the patient will be observed without any treatment. And at visit 4, at 2nd stage, they will be treated with the same regimen for H. pylori eradication.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment arm: H. pylori eradication<br>treatment arm: H. pylori eradication at visit 1(0 month) | Drug: treatment : H. pylori eradication<br>* treatment: H. pylori eradication (pantoprazole, amoxicillin, clarithromycin, metronidazole) to treatment group at visit 1 and to control group 2nd stage at visit 4. Day 1-5: pantoprazole 40mg bid, amoxicillin 1000mg bid, PO Day 6 - 10: pantoprazole 40mg bid, clarithromycin 500mg bid, metronidazole 500mg tid, PO<br>|
| No Intervention: Control arm -1st stage<br>At visit 1(0 month) no intervention, observation only from visit 1 to visit 3 | |
| Active Comparator: Control arm - 2nd stage<br>Same patients group with control arm 1st stage. After observation for 3 months during stage 1, the patients of control arm will be treated with same regimen for H. pylori eradication at visit 4 (2nd stage). | Drug: treatment : H. pylori eradication<br>* treatment: H. pylori eradication (pantoprazole, amoxicillin, clarithromycin, metronidazole) to treatment group at visit 1 and to control group 2nd stage at visit 4. Day 1-5: pantoprazole 40mg bid, amoxicillin 1000mg bid, PO Day 6 - 10: pantoprazole 40mg bid, clarithromycin 500mg bid, metronidazole 500mg tid, PO<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response rate (ORR: complete response + response rate) of platelets | ORR between treatment group with UBT (-) and control group with stage 1 International working group criteria for ITP treatment response will be used for ORR definition | visit 4 (3 months after randomization) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ORR between treatment group and control group with stage 1 | all patients in the treatment group (with UBT (+) or UBT (-) patients) | visit 4 (3 months after randomization) | 
| ORR of control group with stage 2 | patients in the control group with stage 2 with UBT (-) | At visit 5 (6 months after randomization) | 
| ORR after H. pylori eradication in all patients who were treated and UBT (-) | UBT (-) patients in treatment group and control group with stage 2 | 3 months after H. pylori eradication | 
| Time to response | from initiation date of study drugs to the date of R or CR in treatment group | from initiation date of study drugs to the date of R or CR (assessed up to 6 months) | 
| Response duration | from the date of R or CR to the date of loss of R or CR / or till last f/u date in treatment group | from the date of R or CR to the date of loss of R or CR / or till last f/u date, whichever came first (assessed up to 6 months) | 
| H. pylori eradication rate | defined by UBT (-) | at vist 4 (3 months after randomization) after drug treatment | 
| drug toxicity and compliance | NCI CTCAE v4.0 for safety measurement, 85% of taking medicine for criteria of compliance | At visit 2, 3, 4, 5 (1, 2, 3, 6 months after randomization, respectively) for treatment group, at visit 5 (6 months after randomization) for control group stage 2 | 
| QoL | within & between group after H. pylori eradication, FACIT-F, FACIT-Th6 | At visit 1(Day 1 of study drug medication) & vist 4 (3 months after randomization) | 
| platelet level at randomization | comparison of platelet level at randomization between treatment responder and non-responder of H. pylori eradication | 3 months after H. pylori eradication | 
| ITP duration before randomization | comparison of ITP duration before randomization between treatment responder and non-responder of H. pylori eradication | 3 months after H. pylori eradication | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Immune Thrombocytopenic Purpura, Helicobacter pylori