The Combination of Terbutaline 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-label, single center study to assess the efficacy and safety of terbutaline plus danazol in patients with corticosteroid resistant/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. β2-AR agonist terbutaline modulates T cell differentiation and effector cell function. A single center prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were assigned to terbutaline plus danazol group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to assess the efficacy and safety of terbutaline plus danazol in patients with corticosteroid-resistant/relapsed ITP.

Official Title
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The Combination of Terbutaline 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: Terbutaline
* 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; Subject has signed and dated written informed consent. Fertile patients must use effective contraception during treatment and observational period Negative pregnancy test. 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. diagnosis with any of the following diseases: chronic hypertension, hyperthyroidism, diabetes, or seizure disorder.

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: Terbutaline plus Danazol group<br>Terbutaline 2.5mg tid po plus danazol 200mg bid po for 12weeks | Drug: Terbutaline<br>* 2.5mg po tid for 12 weeks<br>* Other names: Bricanyl Brethine;Drug: Danazol<br>* 200mg po bid for 12 weeks<br>* Other names: Danol;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained response | The maintenance of platelet count ≥ 30 x 10^9/L, at least 2-fold increase of the baseline count, the absence of bleeding, and no need for rescue medication at the 6-month follow-up. Interim analysis was scheduled at 50% through recruitment. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| complete remission | The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding. | 6 months | 
| partial remission | The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy. | 6 months | 
| time to response | Time to response was defined as the time from starting treatment to the time to achieve the response. Interim analysis | 6 months | 
| duration of response | Duration of response was measured from the achievement of response to the loss of response. | 6 months | 
| incidence of treatment-emergent adverse events | Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. | 6 months |