H. Pylori Eradication for Moderate ITP

• ClinicalTrials.gov Identifier: NCT03177629
• Recruitment Status: Recruiting
• First Posted: June 6, 2017
• Last Update Posted: September 7, 2018
• Sponsor: Seoul National University Hospital
• Collaborator: Hallym University Medical Center
• Information provided by (Responsible Party): Soo-Mee Bang, Seoul National University Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenic Purpura; Helicobacter Pylori; Immune Thrombocytopenia	Drug: treatment : H. pylori eradication	Phase 3

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 54 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment

Intervention 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)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: May 23, 2017
• Estimated Primary Completion Date: June 2020
• Estimated Study Completion Date: December 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment arm: H. pylori eradication; treatment arm: H. pylori eradication at visit 1(0 month)	Drug: treatment : H. pylori eradication; 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
No Intervention: Control arm -1st stage; At visit 1(0 month) no intervention, observation only from visit 1 to visit 3
Active Comparator: Control arm - 2nd stage; 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; 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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 19 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Soo-Me Bang, M.D.; 82 31 787 7039; smbang7@snu.ac.kr

Contact: HYO JUNG KIM, M.D.; 82 31 380 3704; hemonc@hallym.or.kr

Locations

Korea, Republic of

Seoul National University Bundang Hospital; Recruiting

Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707

Contact: Soo-Mee Bang, M.D. 82 31 787 7039 smbang7@snu.ac.kr

Sponsors and Collaborators

Seoul National University Hospital

Hallym University Medical Center

Investigators

• Principal Investigator: Soo-Me Bang, M.D.; Seoul National University Bundang Hospital

More Information

Publications:

Kim H, Lee WS, Lee KH, Bae SH, Kim MK, Joo YD, Zang DY, Jo JC, Lee SM, Lee JH, Lee JH, Kim DY, Ryoo HM, Hyun MS, Kim HJ; CoOperative Study Group A for Hematology (COSAH). Efficacy of Helicobacter pylori eradication for the 1st line treatment of immune thrombocytopenia patients with moderate thrombocytopenia. Ann Hematol. 2015 May;94(5):739-46. doi: 10.1007/s00277-014-2268-9. Epub 2014 Dec 13.

• Responsible Party: Soo-Mee Bang, Professor, Department of Internal Medicine, Seoul National University Hospital
• ClinicalTrials.gov Identifier: NCT03177629
• Other Study ID Numbers: KSH_ITP1701
• First Posted: June 6, 2017
• Last Update Posted: September 7, 2018
• Last Verified: September 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Soo-Mee Bang, Seoul National University Hospital:

Immune Thrombocytopenic Purpura; Helicobacter pylori

Additional relevant MeSH terms:

Thrombocytopenia; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Blood Platelet Disorders; Hematologic Diseases; Blood Coagulation Disorders; Hemorrhage; Pathologic Processes; Skin Manifestations; Signs and Symptoms; Thrombotic Microangiopathies; Immune System Diseases; Hemorrhagic Disorders; Autoimmune Diseases