Immune Thrombocytopenia
Conditions
Keywords
steroid-resistant, refractory, Atorvastatin, Acetylcysteine, Danazol
Brief summary
Single-arm, open-lable, multicentre study to compare the efficacy and safety of atorvastatin, acetylcysteine plus danazol with danazol monotherapy in patients with corticosteroidresistant/relapsed ITP.
Detailed description
Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. Atorvastatin was shown to enhance bone marrow endothelial cell function and N-acetylcysteine (NAC) was shown to inhibit PLT binding to endothelial cell. A multicentre prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were randomized to atorvastatin, acetylcysteine plus danazol with danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to compare the efficacy and safety of atorvastatin, acetylcysteine plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.
Interventions
DRUGatorvastatin
Atorvastatin was used in combination with acetylcysteine and danazol.
DRUGAcetylcysteine
Acetylcysteine was used in combination with atorvastatin and danazol.
DRUGDanazol
Danazol was used in combination with atorvastatin and acetylcysteine or as the monotherapy
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 No maximum
Healthy volunteers
No
Inclusion criteria
* ITP confirmed by excluding other supervened causes of thrombocytopenia; * Platelet count of less than 30×10\^9/L at enrollment; * Patients who did not achieve a sustained response to treatment with full dose corticosteroids for a minimum duration of 4 weeks or who relapsed during steroid-tapering or after its discontinuation; * ECOG\<2. * EPCs in bone marrow less than 0.02%
Exclusion criteria
* Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus) * congestive heart failure * severe arrhythmia * nursing or pregnant women * aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria * creatinine or serum bilirubin levels each 1.5 times or more than the normal range * active or previous malignancy * Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the sustained platelet response at the 6-month follow-up | From the start of study treatment (Day 1) up to the end of Month 6 | The number of participants (responders) with platelet count \>=30x10\^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count \>=100x10\^9/L (CR) and the absence of bleeding, without rescue medication at 6-month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| overall response | From the start of study treatment (Day 1) up to the end of Month 6 | The number of participants with platelet count \>=30×10\^9/L at least once and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy. |
| time to response | From the start of study treatment (Day 1) up to the end of Year 2 | Time to response was defined as the time from starting treatment to the time to achieve the response. |
| duration of response | From the start of study treatment (Day 1) up to the end of Year 2 | Duration of response was measured from the achievement of response to the loss of response. |
| incidence of treatment-emergent adverse events | From the start of study treatment (Day 1) up to the end of Year 2 | All patients were assessed for treatment-emergent adverse events every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 |
Countries
China
Contacts
Primary ContactXiao-hui Zhang, Professor
Outcome results
None listed