The Combination of Sitagliptin and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

Study Overview
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Brief Summary
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Randomized, open-label, multicenter study to compare the efficacy and safety of combination of Sitagliptin and danazol versus danazol for the treatment of adults with steroid-resistant/relapse immune thrombocytopenia (ITP).

Detailed Description
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The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 120 adults with steroid-resistant/relapse ITP in China. Patients were randomized to Sitagliptin plus danazol and 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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The Combination of Sitagliptin and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: A Randomized, Controlled, Multicenter, Open-label Trial

Conditions
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Immune Thrombocytopenia, Blood Coagulation Disorders, Thrombocytopenia, Physiological Effects of Drugs

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Danazol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia; Platelet count of less than 30×109/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; 18 years older; 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
Maximum Age: 70 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
Interventional Model Description: The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 100 adults with steroid-resistant/ relapse ITP in China. Patients were randomized to Sitagliptin plus danazol and danazol monotherapy group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Sitagliptin and Danazol<br>Sitagliptin is given at a dose of 100 mg/m2 qd for 12 weeks. Danazol is given at 200mg bid for 12 weeks. | Drug: Sitagliptin<br>* Oral Sitagliptin (100mg/m2 daily) for 12 weeks. DPP4 inhibitors have anti-inflammatory, immunomodulatory, and hematopoietic effects in addition to their glycemic regulatory effects. In vivo experiments found that endogenous DPP-4 inhibits megakaryopoiesis, and knockout or inhibition of DPP4 in vivo can enhance the recovery of hematopoietic function after stress. The loss of DPP-4 activity in DPP-4-/-mice mice resulted in an expansion of the megakaryocyte progenitor population in vivo, the recovery time of platelets was shorter than in normal mice after platelet depletion with anti-mouse CD41 antibody. Compared with ordinary mice, the number of platelets increased, which provides a theoretical basis for the use of DPP-4 inhibitors in patients with ITP, and has potential clinical significance.<br>* Other names: JANUVIA;Drug: Danazol<br>* Oral danazol (200 mg twice daily) for 12 weeks.<br>* Other names: Danocrine;|
| Active Comparator: Danazol<br>Danazol is given at 200mg bid for 12 weeks. | Drug: Danazol<br>* Oral danazol (200 mg twice daily) for 12 weeks.<br>* Other names: Danocrine;|

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. | 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Sitagliptin, Immune Thrombocytopenia, Danazol