Clinical trial NCT03909763: Combination of Danazole With Berberine in the Treatment of ITP
Official title: Combination of Danazole With Berberine in the Treatment of ITP
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Corticosteroid-resistant or Relapsed ITP
Keywords: corticosteroid-resistant or relapsed ITP
Danazole
berberine
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2019-04-10
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: The Count of Participants That Achieved 6-month Sustained Response
timeFrame: 6 month
Secondary outcomes:
measure: the Count of Participants That Had Adverse Events
timeFrame: 2 years
measure: the Count of Participants That Achieved Initial Response
timeFrame: 4 weeks
measure: DOR
timeFrame: 2 years
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Institute of Hematology
state: Beijing
Study officials:
affiliation: Peking University of people's hospital
name: Xiaohui Zhang, MD
role: PRINCIPAL_INVESTIGATOR
References: