Combination of Danazole With Berberine in the Treatment of ITP

Study Overview
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Brief Summary
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A prospective, multicenter, open-label, Phase II, single arm, trial performed in 6 departments of hematology in China

Detailed Description
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Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count and mucocutaneous bleeding. Approximately one-third of ITP patients fail to respond to first-line therapies. In addition, a certain amount of the patients relapse and require further therapy after one or more treatment strategies (e.g., thrombopoietin receptor agonists or rituximab). The optimal second-line treatment remains a challenge.Berberine (BBR), an isoquinoline alkaloid derived from plants, is widely used as a nonprescription drug to treat diarrhea. Our previous data demonstrated that gut microbiota dysbiosis may contribute to the development of corticosteroid-resistant ITP. BBR may correct corticosteroid-resistance by modulating the gut microbiota structure, thus being a novel potential second-line candidate to treat ITP. Importantly, the potential clinical benefits of BBR have already been evaluated in various studies using human subjects, and it has been shown to be safe. Danazol is an attenuated androgen that has successfully been used in the treatment of ITP. Considering the side-effects of a regular dose of danazol and that BBR and danazol share disparate mechanisms in the treatment of ITP, we hypothesized that the combination of these two agents might be a promising option to maximize efficacy while minimizing adverse effects. Therefore, we aimed to evaluate the long-term efficacy and safety of berberine plus danazol in patients with corticosteroid-resistant or relapsed ITP.

Official Title
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Combination of Danazole With Berberine in the Treatment of ITP

Conditions
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Corticosteroid-resistant or Relapsed ITP

Intervention / Treatment
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* Drug: Berberine plus danazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinically confirmed immune thrombocytopenic purpura (ITP) newly diagnosed Platelet count less than 30×109/L on two occasions or Platelets above 30×109/L combined with bleeding manifestation Subject is ≥ 18 years and ≤80years Subject has signed and dated written informed consent. Fertile patients must use effective contraception during treatment and observational period Negative pregnancy test Exclusion Criteria: Have an impaired renal function as indicated by a serum creatinine level > 2.0 mg/dL Have an inadequate liver function as indicated by a total bilirubin level > 2.0 mg/dL and/or an aspartate aminotransaminase or alanine aminotransferase level > 3×upper limit of normal Have a New York Heart Classification III or IV heart disease Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures Have active hepatitis B or hepatitis C infection Have a HIV infection Have active infection requiring antibiotic therapy within 7 days prior to study entry Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug Previous treatment with rituximab Previous splenectomy Had previous or concomitant malignant disease Not willing to participate in the study. Expected survival of < 2 years Intolerant to murine antibodies Immunosuppressive treatment within the last month Connective tissue disease Autoimmune hemolytic anemia Patients currently involved in another clinical trial with evaluation of drug treatment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Berberine plus danazol<br>Berberine plus danazol group | Drug: Berberine plus danazol<br>* Oral BBR (0.3g thrice daily) plus oral danazol (200 mg twice daily) for 16 weeks<br>* Other names: HangZhou Mingsheng of China;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Count of Participants That Achieved 6-month Sustained Response | 6-month sustained response defined as platelet count of 30×10⁹/L or more and at least a doubling of baseline platelet count (partial response (PR)), or a platelet count of 100×10⁹/L or more and the absence of bleeding without rescue medication(complete response (CR)) | 6 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the Count of Participants That Had Adverse Events | any adverse events/serious adverse events associated with study drugs and bleeding events | 2 years | 
| the Count of Participants That Achieved Initial Response | Initial response by day 28. Initial response includes partial response (PLT of 30×10⁹/L or more and at least a doubling of baseline platelet count) and complete response (PLT of 100×10⁹/L or more and the absence of bleeding without rescue medication). | 4 weeks | 
| DOR | duration of response (DOR) | 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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corticosteroid-resistant or relapsed ITP, Danazole, berberine