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

Sponsor

Peking University People's Hospital (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT03460808

Collaborator

(none)

200

Enrollment

Location

Arm

57.8

Anticipated Duration (Months)

3.5

Patients Per Site Per Month

Study Details

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

Study Type:

Interventional

Anticipated Enrollment :

200 participants

Allocation:

N/A

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

Anticipated Study Start Date :

Mar 10, 2018

Anticipated Primary Completion Date :

Jan 1, 2020

Anticipated Study Completion Date :

Jan 1, 2023

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

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 [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 [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 [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 [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 [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

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.