Clinical trial NCT03460808: The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
Official title: The Combination of Atorvastatin, Acetylcysteine and Danazol as the Treatment of Steroid-resistant/Relapse Immune Thrombocytopenia
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Immune Thrombocytopenia
Keywords: steroid-resistant
refractory
Atorvastatin
Acetylcysteine
Danazol
Lead sponsor: Peking University People's Hospital
Sponsor class: OTHER
First posted: 2018-03-09
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
measure: the sustained platelet response at the 6-month follow-up
timeFrame: From the start of study treatment (Day 1) up to the end of Month 6
Secondary outcomes:
measure: overall response
timeFrame: From the start of study treatment (Day 1) up to the end of Month 6
measure: time to response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 2
measure: duration of response
timeFrame: From the start of study treatment (Day 1) up to the end of Year 2
measure: incidence of treatment-emergent adverse events
timeFrame: From the start of study treatment (Day 1) up to the end of Year 2
Other outcomes:
Locations:
city: Beijing
country: China
facility: Peking University Insititute of Hematology, Peking University People's Hospital
state: Beijing
Study officials:
References: