Combination of Danazole With Berberine in the Treatment of ITP

Corticosteroid-resistant or Relapsed ITP Clinical Trial

Official title:

Combination of Danazole With Berberine in the Treatment of ITP

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03909763
• Other study ID #: ZXH81470343
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 20, 2016
• Est. completion date: June 30, 2021

Study information

• Verified date: September 2020
• Source: Peking University People's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: June 30, 2021
• Est. primary completion date: December 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Corticosteroid-resistant or Relapsed ITP

Intervention

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

Locations

Country	Name	City	State
China	Peking University Institute of Hematology	Beijing	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Peking University People's Hospital

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The Count of Participants That Achieved 6-month Sustained Response	6-month sustained response defined as platelet count of 30×10?/L or more and at least a doubling of baseline platelet count (partial response (PR)), or a platelet count of 100×10?/L or more and the absence of bleeding without rescue medication(complete response (CR))	6 month
Secondary	the Count of Participants That Had Adverse Events	any adverse events/serious adverse events associated with study drugs and bleeding events	2 years
Secondary	the Count of Participants That Achieved Initial Response	Initial response by day 28. Initial response includes partial response (PLT of 30×10?/L or more and at least a doubling of baseline platelet count) and complete response (PLT of 100×10?/L or more and the absence of bleeding without rescue medication).	4 weeks
Secondary	DOR	duration of response (DOR)	2 years