Autoimmune Thrombocytopenia
Conditions
Keywords
All-trans retinoic acid, primary immune thrombocytopenia, corticosteroid-resistant, refractory, danazol
Brief summary
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.
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. 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.
Interventions
DRUGAll-trans retinoic acid
DRUGDanazol
Sponsors
Beijing Municipal Science & Technology Commission
Beijing Hospital
Qilu Hospital of Shandong University
Navy General Hospital, Beijing
Beijing Tongren Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| the sustained platelet response at the 12-month follow-up | From the start of study treatment (Day 1) up to the end of Month 12 | 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 12-month follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| primary response rate at 4 weeks | From the start of study treatment (Day 1) up to week 4 of treatment | The number of participants with platelet count \>=30×10\^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 4 of treatment |
| primary response rate at 8 weeks | From the start of study treatment (Day 1) up to week 8 of treatment | The number of participants with platelet count \>=30×10\^9/L and at least a doubling of the baseline platelet count without the administration of any other platelet increasing therapy at week 8 of treatment |
| time to response | From the start of study treatment (Day 1) up to the end of month 12 | Time to response was defined as the time from starting treatment to the time to achieve the response. |
| overall response | From the start of study treatment (Day 1) up to the end of Month 12 | 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 |
| reduction in bleeding symptoms | From the start of study treatment (Day 1) up to the end of month 12 | Changes of bleeding after treatment. Bleeding was defined in accordance with the WHO bleeding scale (0, no bleeding; 1, petechiae; 2, mild blood loss; 3, gross blood loss; and 4, debilitating blood loss). |
| safety | From the start of study treatment (Day 1) up to the end of follow-up | All patients were assessed for safety 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 |
| duration of response | From the start of study treatment (Day 1) up to the end of month 12 | Duration of response was measured from the achievement of response to the loss of response. |
Countries
China
Outcome results
None listed