The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia

Single-arm, open-lable, multicentre study to compare the efficacy and safety of atorvastatin, acetylcysteine plus danazol with danazol monotherapy in patients with corticosteroidresistant/relapsed ITP.

Study Overview

• Status: Not yet recruiting
• Conditions: Immune Thrombocytopenia
• Intervention / Treatment: Drug: atorvastatin; Drug: Acetylcysteine; 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. Atorvastatin was shown to enhance bone marrow endothelial cell function and N-acetylcysteine (NAC) was shown to inhibit PLT binding to endothelial cell.

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

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 2; Phase 1

Contacts and Locations

• Study Contact: Name: Xiao-hui Zhang, Professor; Phone Number: +86 010-88324516; Email: zhangxh100@sina.com

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China, 100044
      • 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;
• ECOG<2.
• EPCs in bone marrow less than 0.02%

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.

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: atorvastatin, acetylcysteine & danazol; atorvastatin 20mg qd po plus acetylcysteine 400mg tid po plus danazol 200mg bid po for 12 weeks	Drug: atorvastatin; Atorvastatin was used in combination with acetylcysteine and danazol.; Drug: Acetylcysteine; Acetylcysteine was used in combination with atorvastatin and danazol.; Drug: Danazol; Danazol was used in combination with atorvastatin and acetylcysteine or as the monotherapy; Other Names: Danocrine; Cleregil; Danol

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
the sustained platelet response at the 6-month follow-up	The number of participants (responders) with platelet count >=30x10^9/L and at least a 2-fold increase in the baseline count (PR) or a platelet count >=100x10^9/L (CR) and the absence of bleeding, without rescue medication at 6-month follow-up.	From the start of study treatment (Day 1) up to the end of Month 6

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall response	The number of participants with platelet count >=30×10^9/L at least once and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy.	From the start of study treatment (Day 1) up to the end of Month 6
time to response	Time to response was defined as the time from starting treatment to the time to achieve the response.	From the start of study treatment (Day 1) up to the end of Year 2
duration of response	Duration of response was measured from the achievement of response to the loss of response.	From the start of study treatment (Day 1) up to the end of Year 2
incidence of treatment-emergent adverse events	All patients were assessed for treatment-emergent adverse events every week during the first 8 weeks of treatment, and at 2-week intervals thereafter. Adverse events were scaled according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0	From the start of study treatment (Day 1) up to the end of Year 2

Collaborators and Investigators

• Sponsor: Peking University People's Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): March 10, 2018
• Primary Completion (Anticipated): January 1, 2020
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: March 5, 2018
• First Submitted That Met QC Criteria: March 5, 2018
• First Posted (Actual): March 9, 2018

Study Record Updates

• Last Update Posted (Actual): March 9, 2018
• Last Update Submitted That Met QC Criteria: March 5, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: refractory; Atorvastatin; Acetylcysteine; steroid-resistant; 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; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Enzyme Inhibitors; Antimetabolites; Hormones, Hormone Substitutes, and Hormone Antagonists; Protective Agents; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Respiratory System Agents; Hormone Antagonists; Estrogen Antagonists; Antioxidants; Antidotes; Free Radical Scavengers; Expectorants; Atorvastatin; Danazol; Acetylcysteine; N-monoacetylcystine
• Other Study ID Numbers: Z171100001017084

Drug and device information, study documents

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