The Combination of ATRA and Danazol as Second-line Treatment in Adult Immune Thrombocytopenia
- Conditions
- Autoimmune Thrombocytopenia
- Interventions
- Registration Number
- NCT01667263
- Lead Sponsor
- Peking University People's Hospital
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 130
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description All-trans retinoic acid ＆Danazol Danazol Danazol 400mg po and ATRA 10mg bid po All-trans retinoic acid ＆Danazol All-trans retinoic acid Danazol 400mg po and ATRA 10mg bid po Danazol Danazol Danazol 400mg po
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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
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.
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.
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
Trial Locations
- Locations (5)
Beijing Hospital, Ministry of Health
🇨🇳Beijing, Beijing, China
Beijing Tongren Hospital
🇨🇳Beijing, Beijing, China
Peking University People's Hospital, Peking University Insititute of Hematology
🇨🇳Beijing, Beijing, China
Qilu Hospital, Shandong University
🇨🇳Jinan, Shandong, China
PLA Navy General Hospital
🇨🇳Beijing, Beijing, China