The Combination of Terbutaline and Danazol as the Treatment of Corticosteroid-resistant/Relapse Immune Thrombocytopenia

Phase 2

• Conditions: Immune Thrombocytopenia
• Interventions: Drug: Danazol; Drug: Terbutaline

• Registration Number: NCT05494307
• Lead Sponsor: Peking University People's Hospital

Brief Summary

A randomized, open-label, multicenter study to compare the efficacy and safety of terbutaline plus danazol compared to danazol monotherapy for the second-line treatment of adults with corticosteroid-resistant or relapsed primary immune thrombocytopenia (ITP).

Detailed Description

The investigators are undertaking a parallel group, multicenter, randomized controlled trial of 228 adults with ITP in China. Patients were randomized to terbutaline plus danazol compared to danazol 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: 2022-08
• Study First Submitted: 2022-08-06
• Study First Submitted QC: 2022-08-06
• Last Update Submitted: 2022-08-06
• Study First Posted: 2022-08-09
• Last Update Posted: 2022-08-09
• Study Start: 2022-09-01
• Primary Completion: 2023-09-01
• Study Completion: 2024-02-28

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 228

Inclusion Criteria

Patients >18 years old with corticosteroid-resistant or relapsed ITP who had either a platelet count of <30×10^9/L or a platelet count of <50×10^9/L and clinically significant bleeding.

1. Not achieving a sustained response to therapy with full-dose corticosteroids for a duration of at least 4 weeks or relapsed during the process of corticosteroid tapering or discontinuation;
2. Platelet counts <30×10^9/L or platelet counts < 50×10^9/L and significant bleeding symptoms (WHO bleeding scale 2 or above);
3. Willing and able to sign written informed consent.

Exclusion Criteria

1. Pregnant or lactating women;
2. Secondary ITP (have a known diagnosis of connective tissue diseases, malignancy, active infection, HIV infections or hepatitis B virus or hepatitis C virus infections);
3. Received drugs affecting the platelet counts within 6 months before the screening visit (e.g., chemotherapy, anticoagulants, etc);
4. Severe medical condition (lung, heart, hepatic or renal disorder);
5. Patients who are deemed unsuitable for the study by the investigator.
6. Patients who had hypertension, diabetes mellitus, hyperthyroidism or coronary heart disease.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Danazol monotherapy	Danazol	Danazol: A dose of 200 mg twice daily for 16 weeks
Terbutaline plus danazol	Danazol	Terbutaline: A dose of 2.5 mg three times daily for 16 weeks Danazol: A dose of 200 mg twice daily for 16 weeks
Terbutaline plus danazol	Terbutaline	Terbutaline: A dose of 2.5 mg three times daily for 16 weeks Danazol: A dose of 200 mg twice daily for 16 weeks

Primary Outcome Measures

Name	Time	Method
Overall response	From date of randomization until 1 years or the end of follow-up	Achieving a platelet count ≥ 30 × 10\^9/L confirmed on at least two separate occasions (at least 7 days apart), at least a doubling of the baseline platelet count without any other ITP-specific treatment and the absence of bleeding.

Secondary Outcome Measures

Name	Time	Method
Sustained response	From date of randomization until 1 years or the end of follow-up	maintenance of a platelet count \> 30 × 10\^9/L, an absence of bleeding, and no requirement for any other ITP-specific treatment for 6 consecutive months after achievement of OR
Time to response	From date of randomization until 1 years or the end of follow-up	the time from starting treatment to the time a response was achieved.
Duration of response	From date of randomization until 1 years or the end of follow-up	time from OR until loss of response or until the last follow-up visit
Rescue therapy	From date of randomization until 1 years or the end of follow-up	any new medical intervention taken to increase the platelet count or prevent bleeding events or an increase in the dose of concomitant treatments
Associated factors of treatment failure, OR, SR and remission	From date of randomization until 1 years or the end of follow-up	Factors that are associated with treatment failure, OR, SR and remission
Relapse-free survival	From date of randomization until 1 years or the end of follow-up	the time interval between achievement of OR and relapse or the end of the follow-up
Complete response	From date of randomization until 1 years or the end of follow-up	a platelet count ≥ 100 × 10\^9/L measured on two occasions at least 7 days apart and the absence of bleeding
Number of patients with side effects	From date of randomization until 1 years or the end of follow-up	Number of patients with Medication adverse events.
Relapse	From date of randomization until 1 years or the end of follow-up	Loss of OR
Remission	at 12-month follow-up	a durable platelet count \> 30 × 109/L without bleeding up to 12 months after randomization
Number of patients with bleeding	From date of randomization until 1 years or the end of follow-up	Number of patients with bleeding complication (WHO bleeding score)