The Combination of Tacrolimus and High-dose Dexamethasone as First-line Treatment in Adult 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 High-dose Dexamethasone and Tacrolimus versus High-dose Dexamethasone for the first-line treatment of adults with primary immune thrombocytopenia (ITP).

Detailed Description
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The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 100 adults with ITP in China. Patients were randomized to tacrolimuis plus high-dose dexamethasone and high-dose dexamethasone 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 High-dose Dexamethasone and Tacrolimus Versus High-dose Dexamethasone as the First-Line Treatment of Newly-diagnosed Immune Thrombocytopenia: A Randomized, Controlled, Multicenter, Open-label Trial

Conditions
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ITP, Immune Thrombocytopenia

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed newly-diagnosed, treatment-naive ITP; Platelet counts <30×109/L ; Platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above); Willing and able to sign written informed consent. Exclusion Criteria: Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit; Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ; Current HIV infection or hepatitis B virus or hepatitis C virus infections; Active infection; Maligancy; Severe medical condition (lung, hepatic or renal disorder) other than chronic ITP. Unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure, uncontrolled hypertension or cardiac arrhythmia); Female patients who are nursing or pregnant, who may be pregnant, or who contemplate pregnancy during the study period; a history of clinically significant adverse reactions to previous corticosteroid therapy Have a known diagnosis of other autoimmune diseases, established in the medical history and laboratory findings with positive results for the determination of antinuclear antibodies, anti-cardiolipin antibodies, lupus anticoagulant or direct Coombs test; Patients who are deemed unsuitable for the study by the investigator.

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAC and HD-DXM<br>Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone is repeated in the case of lack of response by day 14). Tacrolimus is given at a dose of 0.03mg/kg·d, and the dose is adjusted to maintain the trough concentration of tacrolimus at approximately 3-5 ng/mL for 12 weeks. | Drug: Dexamethasone<br>* Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone is repeated in the case of lack of response by day 14).<br>* Other names: High-dose Dexamethasone;Drug: Tacrolimus<br>* Tacrolimus is given at a dose of 0.03mg/kg·d, and the dose is adjusted to maintain the trough concentration of tacrolimus at approximately 3-5 ng/mL for 12 weeks.<br>* Other names: TAC;|
| Active Comparator: HD-DXM<br>Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone is repeated in the case of lack of response by day 14) . | Drug: Dexamethasone<br>* Dexamethasone 40 mg per day, 4 consecutive days (the 4-day course of dexamethasone is repeated in the case of lack of response by day 14).<br>* Other names: High-dose Dexamethasone;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Sustained（Durable） 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. | 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Complete response (CR) | Complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding. | Day 14 | 
| Response (R) | Response (R) as platelet count more than 30,000 per cubic millimeter and at least 2-fold increase of the baseline count and absence of bleeding. | Day 14 | 
| Time to response | The time from starting treatment to time of achievement of CR or R. | 6 months | 
| Duration of response (DOR) | Duration of response at 6-month follow up. | 6 months | 
| Loss of response | Platelet counts below 100 x 109/L or bleeding (from CR) or platelet counts below 30 x 109/L, less than 2-fold increase of baseline platelet count or bleeding (from R) | 6 months | 
| Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale | The WHO Bleeding Scale is a measure of bleeding severity with the following grades: grade 0 = no bleeding, grade 1= petechiae, grade 2= mild blood loss, grade 3 = gross blood loss, and grade 4 = debilitating blood loss. | From the start of study treatment (Day 1) up to the end of week 24. | 
| Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ) | In all participants ,use ITP-PAQ to assess the Health Related Quality of Life(HRQoL) before and after treatment. | Time Frame: From the start of study treatment (Day 1) up to the end of week 24. | 
| Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F) | In all participants ,use FACIT-F to assess the Health Related Quality of Life(HRQoL) before and after treatment. | Time Frame: From the start of study treatment (Day 1) up to the end of week 24. | 
| Number of Participants with side effects of the drugs | Side effects of the drugs included fever, headache, serum disease, infection, hypotension, rashes, infection liver injury, hypokalaemia, etc. | Time Frame: From the start of study treatment (Day 1) up to the end of week 24. |