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

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ClinicalTrials.gov Identifier: NCT03460808

Recruitment Status : Not yet recruiting

First Posted : March 9, 2018

Last Update Posted : March 9, 2018

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Sponsor:

Information provided by (Responsible Party):

Xiao-hui Zhang, Peking University People's Hospital

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Immune Thrombocytopenia	Drug: atorvastatin Drug: Acetylcysteine Drug: Danazol	Phase 1 Phase 2

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 Design

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Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	200 participants
Intervention Model:	Single Group Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
Estimated Study Start Date :	March 10, 2018
Estimated Primary Completion Date :	January 1, 2020
Estimated Study Completion Date :	January 1, 2023

Resource links provided by the National Library of Medicine

Genetics Home Reference related topics: Immune thrombocytopenia Thrombotic thrombocytopenic purpura

Drug Information available for: Acetylcysteine Danazol Atorvastatin Atorvastatin calcium

Genetic and Rare Diseases Information Center resources: Immune Thrombocytopenia Idiopathic Thrombocytopenic Purpura

U.S. FDA Resources

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

the sustained platelet response at the 6-month follow-up [ Time Frame: From the start of study treatment (Day 1) up to the end of Month 6 ]
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.

Secondary Outcome Measures :

overall response [ Time Frame: From the start of study treatment (Day 1) up to the end of Month 6 ]
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.
time to response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
Time to response was defined as the time from starting treatment to the time to achieve the response.
duration of response [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
Duration of response was measured from the achievement of response to the loss of response.
incidence of treatment-emergent adverse events [ Time Frame: From the start of study treatment (Day 1) up to the end of Year 2 ]
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

Eligibility Criteria

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Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03460808

Contacts

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Contact: Xiao-hui Zhang, Professor	+86 010-88324516	zhangxh100@sina.com

Locations

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China, Beijing
Peking University Insititute of Hematology, Peking University People's Hospital	Not yet recruiting
Beijing, Beijing, China, 100044
Contact: Xiao-hui Zhang, Professor zhangxh100@sina.com

Sponsors and Collaborators

Peking University People's Hospital

More Information

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Responsible Party:	Xiao-hui Zhang, Professor, Peking University People's Hospital
ClinicalTrials.gov Identifier:	NCT03460808 History of Changes
Other Study ID Numbers:	Z171100001017084
First Posted:	March 9, 2018 Key Record Dates
Last Update Posted:	March 9, 2018
Last Verified:	March 2018

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Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Xiao-hui Zhang, Peking University People's Hospital:


steroid-resistant refractory Atorvastatin Acetylcysteine Danazol

Additional relevant MeSH terms:

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Thrombocytopenia Purpura, Thrombocytopenic, Idiopathic Pathologic Processes Blood Platelet Disorders Hematologic Diseases Purpura, Thrombocytopenic Purpura Blood Coagulation Disorders Thrombotic Microangiopathies Hemorrhagic Disorders Autoimmune Diseases Immune System Diseases Hemorrhage Skin Manifestations Signs and Symptoms	Acetylcysteine Atorvastatin N-monoacetylcystine Danazol Anticholesteremic Agents Hypolipidemic Agents Antimetabolites Molecular Mechanisms of Pharmacological Action Lipid Regulating Agents Hydroxymethylglutaryl-CoA Reductase Inhibitors Enzyme Inhibitors Antiviral Agents Anti-Infective Agents Expectorants Respiratory System Agents

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