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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05471050

Collaborator

(none)

120

Enrollment

Location

Arms

Anticipated Duration (Months)

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Immune Thrombocytopenia	Drug: TAC Drug: Danazol	Phase 2

Detailed Description

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

The investigators are undertaking a randomized controlled trial of 120 adults with steroid-resistant/ relapse ITP in China. Patients were randomized to tacrolimus 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.The investigators are undertaking a randomized controlled trial of 120 adults with steroid-resistant/ relapse ITP in China. Patients were randomized to tacrolimus 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)

Primary Purpose:

Treatment

Official Title:

The Combination of Tacrolimus and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia: A Randomized, Controlled, Open-label Trial

Actual Study Start Date :

Mar 2, 2022

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Jun 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: tacrolimus and Danazol 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: TAC 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: Danazol Danazol is given at 200mg bid for 12 weeks.
Active Comparator: Danazol Danazol is given at 200mg bid for 12 weeks.	Drug: Danazol Danazol is given at 200mg bid for 12 weeks.

Arm

Intervention/Treatment

Experimental: tacrolimus and Danazol

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: TAC

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: Danazol

Danazol is given at 200mg bid for 12 weeks.

Active Comparator: Danazol

Danazol is given at 200mg bid for 12 weeks.

Drug: Danazol

Danazol is given at 200mg bid for 12 weeks.

Outcome Measures

Primary Outcome Measures

Sustained response [6 months]
Sustained response was defines as the maintenance of platelet count ≥ 30 x 10^9/L, and at least 2-fold increase of the baseline count, and the absence of bleeding, and no need for rescue medication at the 6-month follow-up.

Secondary Outcome Measures

Complete response [6 months]
Complete response was defines as the maintenance of platelet count ≥ 100 x 10^9/L, and at least 2-fold increase of the baseline count, and the absence of bleeding, and no need for rescue medication.
Response [6 months]
Response was defines as the maintenance of platelet count ≥ 30 x 10^9/L, and at least 2-fold increase of the baseline count, and the absence of bleeding, and no need for rescue medication.
Time to response [6 months]
Time to response was defined as the time from starting treatment to the time to achieve the response.
Duration of response [6 months]
Duration of response was measured from the achievement of response to the loss of response.
Adverse events [6 months]
Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 70 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Primary immune thrombocytopenia (ITP);
18 years older;
Platelet count of less than 30×10^9/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;
Patients who were receiving other maintenance regimens, primarily corticosteroids, ciclosporin, or mycophenolate mofetil, were also eligible if the dose of treatment had been stable in the past month and the dose was expected to be stable after enrolment and remained unchanged at least for the first 4 weeks of study until initial response was assessed, unless severe adverse events were suspected.

Exclusion Criteria:

Secondary ITP (e.g., patients with HIV, HBV, HCV, Helicobacter pylori infection or SLE);
Congestive heart failure, severe arrhythmia;
Nursing or pregnant women;
ALT or AST levels ≥ 3× the upper limit of the normal threshold;
Creatinine or serum bilirubin levels ≥ 1.5× the upper limit;
Active or previous malignancy ;
Patients who had received danazol treatment or did not respond to danazol;
Patients unable to have routine blood tests because of reasons such as insufficient time.