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

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

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).

Study Overview

• Status: Recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: TAC; Drug: Danazol

Detailed 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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiao-Hui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh@bjmu.edu.cn
• Study Contact Backup: Name: Xuan Cai, MD; Phone Number: +8618811729606; Email: 2206385254@qq.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Insititute of Hematology, Peking University People's Hospital
      • Contact: Xiao-Hui Zhang, MD; Phone Number: +8613522338836; Email: zhangxh@bjmu.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained response	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.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
Complete response	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.	6 months
Response	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.	6 months
Adverse events	Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.	6 months

Collaborators and Investigators

• Sponsor: Peking University People's Hospital
• Investigators: Principal Investigator: Xiao-hui Zhang, MD, Peking University People's Hospital, Peking University Insititute of Hematology

Study record dates

Study Major Dates

• Study Start (ACTUAL): March 2, 2022
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): June 1, 2023

Study Registration Dates

• First Submitted: July 17, 2022
• First Submitted That Met QC Criteria: July 20, 2022
• First Posted (ACTUAL): July 22, 2022

Study Record Updates

• Last Update Posted (ACTUAL): July 22, 2022
• Last Update Submitted That Met QC Criteria: July 20, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Keywords: Immune Thrombocytopenia; tacrolimus; danazol
• Additional Relevant MeSH Terms: Pathologic Processes; Immune System Diseases; Autoimmune Diseases; Hematologic Diseases; Hemorrhage; Hemorrhagic Disorders; Blood Coagulation Disorders; Skin Manifestations; Blood Platelet Disorders; Thrombotic Microangiopathies; Purpura, Thrombocytopenic; Purpura; Purpura, Thrombocytopenic, Idiopathic; Thrombocytopenia; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Estrogen Antagonists; Danazol
• Other Study ID Numbers: PKU-ITP036

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No