The Combination of Terbutaline and Danazol as the Treatment of Corticosteroid-resistant/Relapse Immune Thrombocytopenia

Study Overview
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Brief Summary
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A randomized, open-label, multicenter study to compare the efficacy and safety of terbutaline plus danazol compared to danazol monotherapy for the second-line treatment of adults with corticosteroid-resistant or relapsed primary immune thrombocytopenia (ITP).

Detailed Description
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The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 228 adults with ITP in China. Patients were randomized to terbutaline plus danazol compared to danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.

Official Title
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A Multicenter Randomized Trial of Second Line Treatment for Corticosteroid-Resistant or Relapsed Immune Thrombocytopenia: Combined Terbutaline and Danazol Versus Danazol Monotherapy

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: Patients >18 years old with corticosteroid-resistant or relapsed ITP who had either a platelet count of <30×10^9/L or a platelet count of <50×10^9/L and clinically significant bleeding. Not achieving a sustained response to therapy with full-dose corticosteroids for a duration of at least 4 weeks or relapsed during the process of corticosteroid tapering or discontinuation; Platelet counts <30×10^9/L or platelet counts < 50×10^9/L and significant bleeding symptoms (WHO bleeding scale 2 or above); Willing and able to sign written informed consent. Exclusion Criteria: Pregnant or lactating women; Secondary ITP (have a known diagnosis of connective tissue diseases, malignancy, active infection, HIV infections or hepatitis B virus or hepatitis C virus infections); Received drugs affecting the platelet counts within 6 months before the screening visit (e.g., chemotherapy, anticoagulants, etc); Severe medical condition (lung, heart, hepatic or renal disorder); Patients who are deemed unsuitable for the study by the investigator. Patients who had hypertension, diabetes mellitus, hyperthyroidism or coronary heart disease.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Terbutaline plus danazol<br>Terbutaline: A dose of 2.5 mg three times daily for 16 weeks Danazol: A dose of 200 mg twice daily for 16 weeks | Drug: Terbutaline<br>* Orally terbutaline at a dose of 2.5 mg three times daily for 16 weeks<br>Drug: Danazol<br>* Orally danazol at a dose of 200 mg twice daily for 16 weeks<br>|
| Active Comparator: Danazol monotherapy<br>Danazol: A dose of 200 mg twice daily for 16 weeks | Drug: Danazol<br>* Orally danazol at a dose of 200 mg twice daily for 16 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall response | Achieving a platelet count ≥ 30 × 10^9/L confirmed on at least two separate occasions (at least 7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment and the absence of bleeding. | From date of randomization until 1 years or the end of follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained response | maintenance of a platelet count > 30 × 10^9/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR | From date of randomization until 1 years or the end of follow-up | 
| Complete response | a platelet count ≥ 100 × 10^9/L measured on two occasions at least 7 days apart and the absence of bleeding | From date of randomization until 1 years or the end of follow-up | 
| Remission | a durable platelet count > 30 × 109/L without bleeding up to 12 months after randomization | at 12-month follow-up | 
| Time to response | the time from starting treatment to the time a response was achieved. | From date of randomization until 1 years or the end of follow-up | 
| Duration of response | time from OR until loss of response or until the last follow-up visit | From date of randomization until 1 years or the end of follow-up | 
| Rescue therapy | any new medical intervention taken to increase the platelet count or prevent bleeding events or an increase in the dose of concomitant treatments | From date of randomization until 1 years or the end of follow-up | 
| Associated factors of treatment failure, OR, SR and remission | Factors that are associated with treatment failure, OR, SR and remission | From date of randomization until 1 years or the end of follow-up | 
| Number of patients with bleeding | Number of patients with bleeding complication (WHO bleeding score) | From date of randomization until 1 years or the end of follow-up | 
| Number of patients with side effects | Number of patients with Medication adverse events. | From date of randomization until 1 years or the end of follow-up | 
| Relapse | Loss of OR | From date of randomization until 1 years or the end of follow-up | 
| Relapse-free survival | the time interval between achievement of OR and relapse or the end of the follow-up | From date of randomization until 1 years or the end of follow-up |