Combination of Danazole With Berberine in the Treatment of ITP

Peking University People's Hospital55 enrolled

Overview

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

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.

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Corticosteroid-resistant or Relapsed ITP

Interventions

Berberine plus danazolDRUG

Oral BBR (0.3g thrice daily) plus oral danazol (200 mg twice daily) for 16 weeks

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Clinically confirmed immune thrombocytopenic purpura (ITP) newly diagnosed 2. Platelet count less than 30×109/L on two occasions or Platelets above 30×109/L combined with bleeding manifestation 3. Subject is ≥ 18 years and ≤80years 4. Subject has signed and dated written informed consent. 5. Fertile patients must use effective contraception during treatment and observational period 6. Negative pregnancy test Exclusion Criteria: 1. Have an impaired renal function as indicated by a serum creatinine level \> 2.0 mg/dL 2. 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 3. Have a New York Heart Classification III or IV heart disease 4. Have a history of severe psychiatric disorder or are unable to comply with study and follow-up procedures 5. Have active hepatitis B or hepatitis C infection 6. Have a HIV infection 7. Have active infection requiring antibiotic therapy within 7 days prior to study entry 8. Are pregnant or lactating women, or plan to become pregnant or impregnated within 12 months of receiving study drug 9. Previous treatment with rituximab 10. Previous splenectomy 11. Had previous or concomitant malignant disease 12. Not willing to participate in the study. 13. Expected survival of \< 2 years 14. Intolerant to murine antibodies 15. Immunosuppressive treatment within the last month 16. Connective tissue disease 17. Autoimmune hemolytic anemia 18. Patients currently involved in another clinical trial with evaluation of drug treatment

Locations (1)

Peking University Institute of Hematology

Beijing, Beijing Municipality, China

Outcomes

Primary Outcomes

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))

Time frame: 6 month

Secondary Outcomes

the Count of Participants That Had Adverse Events

any adverse events/serious adverse events associated with study drugs and bleeding events

Time frame: 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).

Time frame: 4 weeks

DOR

duration of response (DOR)

Time frame: 2 years

Data from ClinicalTrials.gov

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