H. Pylori Eradication for Moderate ITP

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

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.

Study Overview

• Status: Unknown
• Conditions: Immune Thrombocytopenia; Immune Thrombocytopenic Purpura; Helicobacter Pylori
• Intervention / Treatment: Drug: treatment : H. pylori eradication

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 Type: Interventional
• Enrollment (Anticipated): 54
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Soo-Me Bang, M.D.; Phone Number: 82 31 787 7039; Email: smbang7@snu.ac.kr
• Study Contact Backup: Name: HYO JUNG KIM, M.D.; Phone Number: 82 31 380 3704; Email: hemonc@hallym.or.kr

Study Locations

• Korea, Republic of
  • Gyeonggi-do
    • Seongnam-si, Gyeonggi-do, Korea, Republic of, 463-707
      • Recruiting
      • Seoul National University Bundang Hospital
      • Contact: Soo-Mee Bang, M.D.; Phone Number: 82 31 787 7039; Email: smbang7@snu.ac.kr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 19 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

3

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seoul National University Hospital
• Collaborators: Hallym University Medical Center
• Investigators: Principal Investigator: Soo-Me Bang, M.D., Seoul National University Bundang Hospital

Publications and helpful links

General 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.
• Han B, Kim HJ, Yhim HY, Oh D, Bae SH, Shin HJ, Lee WS, Kwon J, Lee JO, Kim HJ, Bang SM. Sequential eradication of Helicobacter pylori as a treatment for immune thrombocytopenia in patients with moderate thrombocytopenia: a multicenter prospective randomized phase 3 study. Ann Hematol. 2022 Jul;101(7):1435-1445. doi: 10.1007/s00277-022-04782-2. Epub 2022 May 28.

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 23, 2017
• Primary Completion (ANTICIPATED): June 1, 2020
• Study Completion (ANTICIPATED): December 1, 2020

Study Registration Dates

• First Submitted: May 29, 2017
• First Submitted That Met QC Criteria: June 5, 2017
• First Posted (ACTUAL): June 6, 2017

Study Record Updates

• Last Update Posted (ACTUAL): September 7, 2018
• Last Update Submitted That Met QC Criteria: September 5, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Keywords: Helicobacter pylori; Immune Thrombocytopenic Purpura
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura; Purpura, Thrombocytopenic; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia
• Other Study ID Numbers: KSH_ITP1701

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