The Combination of Tacrolimus and High-dose Dexamethasone as First-line Treatment in Adult Immune Thrombocytopenia

Phase 2

• Conditions: ITP; Immune Thrombocytopenia
• Interventions: Drug: Dexamethasone; Drug: Tacrolimus

• Registration Number: NCT04747080
• Lead Sponsor: Peking University People's Hospital

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-02
• Study First Submitted: 2021-02-05
• Study First Submitted QC: 2021-02-05
• Last Update Submitted: 2021-02-05
• Study First Posted: 2021-02-10
• Last Update Posted: 2021-02-10
• Study Start: 2021-03-01
• Primary Completion: 2023-03-01
• Study Completion: 2023-07-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 120

Inclusion Criteria

1. Confirmed newly-diagnosed, treatment-naive ITP;
2. Platelet counts <30×109/L ;
3. Platelet counts < 50×109/L and significant bleeding symptoms (WHO bleeding scale 2 or above);
4. Willing and able to sign written informed consent.

Exclusion Criteria

1. Received chemotherapy or anticoagulants or other drugs affecting the platelet counts within 6 months before the screening visit;
2. Received first-line and second-line ITP-specific treatments (eg, steriods, cyclophosphamide, 6-mercaptopurine, vincristine, vinblastine, etc) ;
3. Current HIV infection or hepatitis B virus or hepatitis C virus infections;
4. Active infection;
5. Maligancy;
6. 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);
7. 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
8. 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;
9. Patients who are deemed unsuitable for the study by the investigator.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
TAC and HD-DXM	Dexamethasone	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.
HD-DXM	Dexamethasone	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) .
TAC and HD-DXM	Tacrolimus	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.

Primary Outcome Measures

Name	Time	Method
Sustained（Durable） response	6 months	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.

Secondary Outcome Measures

Name	Time	Method
Complete response (CR)	Day 14	Complete response (CR) was defined as platelet count more than 100,000 per cubic millimeter and absence of bleeding.
Response (R)	Day 14	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.
Duration of response (DOR)	6 months	Duration of response at 6-month follow up.
Number of participants with clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale	From the start of study treatment (Day 1) up to the end of week 24.	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.
Time to response	6 months	The time from starting treatment to time of achievement of CR or R.
Loss of response	6 months	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)
Immune Thrombocytopenia Patient Assessment Questionnaire (ITP-PAQ)	Time Frame: From the start of study treatment (Day 1) up to the end of week 24.	In all participants ,use ITP-PAQ to assess the Health Related Quality of Life(HRQoL) before and after treatment.
Functional Assessment of Chronic Illness Therapy fatigue subscale (FACIT-F)	Time Frame: From the start of study treatment (Day 1) up to the end of week 24.	In all participants ,use FACIT-F to assess the Health Related Quality of Life(HRQoL) before and after treatment.
Number of Participants with side effects of the drugs	Time Frame: From the start of study treatment (Day 1) up to the end of week 24.	Side effects of the drugs included fever, headache, serum disease, infection, hypotension, rashes, infection liver injury, hypokalaemia, etc.

Trial Locations

Locations (1)

Peking University People's Hospital; 🇨🇳 Beijing, China