The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

Study Overview
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Brief Summary
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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
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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.

Official Title
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The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: atorvastatin
* Drug: Acetylcysteine
* Drug: Danazol


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: atorvastatin, acetylcysteine & danazol<br>atorvastatin 20mg qd po plus acetylcysteine 400mg tid po plus danazol 200mg bid po for 12 weeks | Drug: atorvastatin<br>* Atorvastatin was used in combination with acetylcysteine and danazol.<br>Drug: Acetylcysteine<br>* Acetylcysteine was used in combination with atorvastatin and danazol.<br>Drug: Danazol<br>* Danazol was used in combination with atorvastatin and acetylcysteine or as the monotherapy<br>* Other names: Danol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the sustained platelet response at the 6-month follow-up | 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. | From the start of study treatment (Day 1) up to the end of Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| overall response | 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. | From the start of study treatment (Day 1) up to the end of Month 6 | 
| time to response | Time to response was defined as the time from starting treatment to the time to achieve the response. | From the start of study treatment (Day 1) up to the end of Year 2 | 
| duration of response | Duration of response was measured from the achievement of response to the loss of response. | From the start of study treatment (Day 1) up to the end of Year 2 | 
| incidence of treatment-emergent adverse events | 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 | From the start of study treatment (Day 1) up to the end of Year 2 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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steroid-resistant, refractory, Atorvastatin, Acetylcysteine, Danazol