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

Single-arm, open-label, single center study to assess the efficacy and safety of terbutaline plus danazol in patients with corticosteroid resistant/relapsed ITP.

Study Overview

• Status: Unknown
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: Terbutaline; Drug: Danazol

Detailed Description

Immune thrombocytopenia (ITP) is a severe bleeding disorder. Approximately 2/3 of patients achieve remission from first-line therapies. However, the underlying mechanism of corticosteroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. β2-AR agonist terbutaline modulates T cell differentiation and effector cell function.

A single center prospective study was performed in non-splenectomized ITP patients who were either resistant to a standard dose of corticosteroids or had relapsed. Patients were assigned to terbutaline plus danazol group. Platelet count, bleeding and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study, in order to assess the efficacy and safety of terbutaline plus danazol in patients with corticosteroid-resistant/relapsed ITP.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Xiaohui Zhang, MD; Phone Number: 010-88324981; Email: zhangxh100@sina.com
• Study Contact Backup: Name: Gaochao Zhang, phD; Phone Number: +8618053803755; Email: zhanggaochao0210@163.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100010
      • Recruiting
      • Peking University Insititute of Hematology, Peking University People's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ITP confirmed by excluding other supervened causes of thrombocytopenia;
• 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;
• Subject has signed and dated written informed consent.
• Fertile patients must use effective contraception during treatment and observational period
• Negative pregnancy test.

Exclusion Criteria:

• Secondary immune thrombocytopenia (e.g., patients with HIV, HCV, Helicobacter pylori infection or patients with systemic lupus erythematosus)
• congestive heart failure
• severe arrhythmia
• nursing or pregnant women
• aspartate aminotransferase and alanine transaminase levels ≥ 3× the upper limit of the normal threshold criteria
• creatinine or serum bilirubin levels each 1•5 times or more than the normal range
• active or previous malignancy
• Unable to do blood routine test for the sake of time, distance, economic issues or other reasons.
• diagnosis with any of the following diseases: chronic hypertension, hyperthyroidism, diabetes, or seizure disorder.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Terbutaline plus Danazol group; Terbutaline 2.5mg tid po plus danazol 200mg bid po for 12weeks	Drug: Terbutaline; 2.5mg po tid for 12 weeks; Other Names: Bricanyl Brethine; Drug: Danazol; 200mg po bid for 12 weeks; Other Names: Danocrine; Cleregil; Danol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sustained 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. Interim analysis was scheduled at 50% through recruitment.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
complete remission	The number of participants (responders) with platelet count>=100x10^9/L (CR) and the absence of bleeding.	6 months
partial remission	The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) without the administration of any other platelet increasing therapy.	6 months
time to response	Time to response was defined as the time from starting treatment to the time to achieve the response. Interim analysis	6 months
duration of response	Duration of response was measured from the achievement of response to the loss of response.	6 months
incidence of treatment-emergent 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

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Anticipated): March 31, 2021
• Study Completion (Anticipated): July 31, 2021

Study Registration Dates

• First Submitted: July 19, 2020
• First Submitted That Met QC Criteria: July 21, 2020
• First Posted (Actual): July 22, 2020

Study Record Updates

• Last Update Posted (Actual): July 22, 2020
• Last Update Submitted That Met QC Criteria: July 21, 2020
• Last Verified: July 1, 2020

More Information

Terms related to this study

• 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; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Hormones, Hormone Substitutes, and Hormone Antagonists; Adrenergic Agonists; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Hormone Antagonists; Estrogen Antagonists; Reproductive Control Agents; Adrenergic beta-2 Receptor Agonists; Adrenergic beta-Agonists; Tocolytic Agents; Sympathomimetics; Danazol; Terbutaline
• Other Study ID Numbers: ITP-PKU010

Drug and device information, study documents

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