A Multicenter Randomized Open-label Study of Diammonium Glycyrrhizinate Enteric-coated Capsule Plus DXM Versus DXM in Treatment of ITP

Study Overview
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Brief Summary
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The project was undertaking by Qilu Hospital of Shandong University in China. In order to report the efficacy and safety of diammonium glycyrrhizinate enteric-coated capsule plus high-dose dexamethasone for the treatment of adults with newly-diagnosed primary immune thrombocytopenia (ITP).

Detailed Description
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The investigators anticipate to undertaking a parallel group, randomised controlled trial of 106 ITP patients. One part of the participants are randomly selected to receive diammonium glycyrrhizinate enteric-coated capsule orally at a dose of 150mg tid for 3 months), combining with dexamethasone (given orally at a dose of 40 mg qd for 4 days). The others are selected to receive high-dose of dexamethasone alone. Patients who do not respond to the treatment may receive another cycle of high-dose dexamethasone therapy with an interval of 10 days. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study. The purpose of this study is to report the efficacy and safety of diammonium glycyrrhizinate enteric-coated capsule combining with high-dose dexamethasone therapy for the treatment of ITP.

Official Title
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High-dose Dexamethasone Plus Diammonium Glycyrrhizinate Enteric-coated Capsule Versus High-dose Dexamethasone in Treatment-naive Primary Immune Thrombocytopenia (ITP): a Multicentre, Randomised, Open-label Trial

Conditions
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Immune Thrombocytopenia

Intervention / Treatment
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* Drug: dexamethasone
* Drug: diammonium glycyrrhizinate enteric-coated capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Meet the diagnostic criteria for immune thrombocytopenia; Untreated hospitalized patients or patients from the clinic, may be male or female, between the ages of 18  80 years; To show a platelet count <30 * 10^9/L, or with bleeding manifestations, or both; Willing and able to sign written informed consent ITP patients with hepatitis virus infection or ITP patients with abnormal liver function at the time of enrollment, i.e., ITP patients with indications for diammonium glycyrrhizinate enteric-coated capsule, should be separately stratified. Exclusion Criteria: secondary thrombocytopenia; severe immune-deficiency; active or previous malignancy; HIV virus infection, tuberculosis, or other active infection (sepsis, pneumonia, or abscess); pregnancy or lactation; diabetes; hypertension; cardiovascular diseases; severe kidney function impairment; psychosis; osteoporosis; inflammatory bowel disease or gastric disease; arterial or venous thromboembolism within the 6 months before screening or patients who required anticoagulant treatment; an organ or haematopoietic stem-cell transplantation; neutrophil count of less than 1500 cells per mm³; glycosylated haemoglobin less than 8%; partial thromboplastin time 1∙5 times or less the upper limit of normal (ULN); •clinical electrocardiogram changes; history of primary immunodeficiency; neoplastic disease within the past 5 years; corrected QT interval greater than 450 ms for men and greater than 470 ms for women; substance misuse within the previous 12 months; people who could not adhere to the protocol or were planning to have a surgical procedure in 6 months.

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: diammonium glycyrrhizinate enteric-coated capsule + high-dose dexamethasone<br>Diammonium glycyrrhizinate enteric-coated capsule orally at a dose of 150mg tid for 3 months, combining with dexamethasone (given orally at a dose of 40 mg qd for 4 days). Patients who do not respond to the treatment may receive another cycle of high-dose dexamethasone therapy with an interval of 10 days. | Drug: dexamethasone<br>* 40 mg qd for 4 days<br>Drug: diammonium glycyrrhizinate enteric-coated capsule<br>* 150mg tid for 3 months<br>|
| Active Comparator: High-dose dexamethasone<br>Dexamethasone orally at a dose of 40 mg qd for 4 days. Patients who do not respond to the treatment may receive another cycle of high-dose dexamethasone therapy with an interval of 10 days. | Drug: dexamethasone<br>* 40 mg qd for 4 days<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 14-day initial overall response to ITP treatments | Complete response was defined as a platelet count of 100×10⁹ cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10⁹ cells per L or higher, but less than 100×10⁹ cells per L, and at least a doubling of the baseline platelet count and an absence of bleeding. Platelet counts were confirmed on two separate occasions at least 7 days apart when defining complete response or partial response. No response was defined as a platelet count of less than 30×10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding. | 14 days after treatment started | 
| 6-month sustained overall response to ITP treatments | Complete response was defined as a platelet count of 100×10⁹ cells per L or higher and an absence of bleeding. Partial response was defined as a platelet count of 30×10⁹ cells per L or higher, but less than 100×10⁹ cells per L, and at least a doubling of the baseline platelet count and an absence of bleeding. Platelet counts were confirmed on two separate occasions at least 7 days apart when defining complete response or partial response. No response was defined as a platelet count of less than 30×10⁹ cells per L, or less than two-times increase from baseline platelet count, or bleeding. | A response lasting for at least 6 months without any additional intervention specific to primary immune thrombocytopenia was defined as a sustained response | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| time to response | the time from treatment initiation to achieve a complete response or a partial response | an average of 6 months | 
| duration of response | the time from achievement of a complete response or a partial response to the loss of response (platelet count <30×10⁹ cells per L; measured on two occasions more than 1 day apart or the presence of bleeding). | through study completion, an average of one year | 
| therapy associated adverse events | nausea and diarrhea (report in frequency); pruritus (report in frequency); headache and dizziness (report in frequency) | up to one year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dexamethasone, Diammonium Glycyrrhizinate Enteric-coated Capsule