Corticosteroid-resistant or Relapsed ITP
Conditions
Keywords
corticosteroid-resistant or relapsed ITP, Danazole, berberine
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.
Interventions
DRUGBerberine plus danazol
Oral BBR (0.3g thrice daily) plus oral danazol (200 mg twice daily) for 16 weeks
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Count of Participants That Achieved 6-month Sustained Response | 6 month | 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)) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| the Count of Participants That Had Adverse Events | 2 years | any adverse events/serious adverse events associated with study drugs and bleeding events |
| the Count of Participants That Achieved Initial Response | 4 weeks | 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). |
| DOR | 2 years | duration of response (DOR) |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Berberine Plus Danazol Berberine plus danazol group
Berberine plus danazol: Oral BBR (0.3g thrice daily) plus oral danazol (200 mg twice daily) for 16 weeks | 45 |
| Total | 45 |
Baseline characteristics
| Characteristic | Berberine Plus Danazol | — |
|---|---|---|
| Age, Continuous | 45 years | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Sex: Female, Male Female | 29 Participants | — |
| Sex: Female, Male Male | 16 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 45 |
| other Total, other adverse events | 4 / 45 |
| serious Total, serious adverse events | 1 / 45 |
Outcome results
Primary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Berberine Plus Danazol | The Count of Participants That Achieved 6-month Sustained Response | 28 Participants |
Secondary
DOR
duration of response (DOR)
Time frame: 2 years
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Berberine Plus Danazol | DOR | 9.2 months | Standard Deviation 10.731 |
Secondary
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
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Berberine Plus Danazol | the Count of Participants That Achieved Initial Response | 21 Participants |
Secondary
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
| Arm | Measure | Category | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Berberine Plus Danazol | the Count of Participants That Had Adverse Events | Adverse events associated with study drugs | 4 Participants |
| Berberine Plus Danazol | the Count of Participants That Had Adverse Events | Bleeding events | 1 Participants |
| Berberine Plus Danazol | the Count of Participants That Had Adverse Events | No adverse events | 40 Participants |