The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia

Peking University

Status and phase: Completed; Phase 2

Conditions: Autoimmune Thrombocytopenia

Treatments: Drug: Danazol; Drug: All-trans retinoic acid

Study type: Interventional

Funder types: Other

Identifiers

NCT01667263

U1111-1132-6877

Z111107058811024 (Other Grant/Funding Number)

Details and patient eligibility

About

Randomized, open-label, multicentre study to compare the efficacy and safety of ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.

Full 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. All-trans retinoic acid (ATRA) has an immunomodulatory effect on haematopoiesis, making it a possible treatment option.

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 ATRA+danazol and 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 ATRA plus danazol with danazol monotherapy in patients with corticosteroid-resistant/relapsed ITP.

Enrollment: 130 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Primary immune thrombocytopenia (ITP) confirmed by excluding other supervened causes of thrombocytopenia;
• Platelet count of less than 30×109/L at enrolment
• 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.
• 18 years older.

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

130 participants in 2 patient groups

All-trans retinoic acid ＆Danazol

Experimental group

Description:

Danazol 400mg po and ATRA 10mg bid po

Treatment:

Drug: All-trans retinoic acid

Drug: Danazol

Danazol

Active Comparator group

Description:

Danazol 400mg po

Treatment:

Drug: Danazol