Immune Thrombocytopenia (ITP)
Conditions
Keywords
Iguratimod
Brief summary
Randomized, open-label, multicentre study to assess the efficacy and safety of the combination of low-dose rituximab and Iguratimod in patients with steroid-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 steroid-resistant or relapsed ITP is not well understood; thus, treatment remains a great challenge. Rituximab has been shown to partly improve the complete remission rate of ITP. The small molecule compound iguratimod is widely used as a novel antirheumatic drug to treat several autoimmune diseases. According to studies involving ITP mice, iguratimod may represent a new approach for the prevention and treatment of anti-platelet antibody-mediated ITP by modulating T-cell differentiation. 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 the low-dose rituximab+iguratimod and the low-dose rituximab monotherapy groups. Platelet count, bleeding and other symptoms were evaluated before and after treatment.Adverse events are also recorded throughout the study, in order to assess the efficacy and safety of the combination of low-dose rituximab and iguratimod in patients with steroid-resistant/relapsed ITP.
Interventions
DRUGIguratimod
oral iguratimod at 25mg twice daily for 26 weeks
DRUGlow-dose rituximab
rituximab 100mg once weekly for 6 weeks
Sponsors
Beijing Hospital
Beijing Friendship Hospital
Navy General Hospital, Beijing
Beijing Tongren Hospital
Peking University People's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Intervention model description
Patients are randomly assigned at a 1:1 ratio to receive Iguratimod plus low-dose rituximab or high-dose rituximab alone. Each group requires 60 patients.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
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;
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; * Patients with other diseases were undergoing treatment with immunosuppressants; * Patients with ITP had received rituximab;
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| overall response | From the start of study treatment (Day 1) up to the end of Year 1 | 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 1-year follow-up. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| complete response | From the start of study treatment (Day 1) up to the end of Year 1 | The number of participants (responders) with platelet count\>=100x10\^9/L (CR) and the absence of bleeding, without rescue medication at 1-year follow-up. |
| time to response | From the start of study treatment (Day 1) up to the end of Year 1 | 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 1 | Duration of response was measured from the achievement of response to the loss of response. |
| sustained response | From the start of study treatment (Day 1) up to the end of Year 1 | The number of participants that can maintain the platelet count \> 30 x 109/L, an absence of bleeding events, and without requirement for any other ITP-specific treatment for 6 consecutive months after achievement of response. |
| Bleeding events | From the start of study treatment (Day 1) up to the end of Year 1 | Clinically significant bleeding as assessed using the world health organization (WHO) bleeding scale. |
| Health-related quality of life (HRQoL) | From the start of study treatment (Day 1) up to the end of Year 1 | ITP-PAQ is used to assess the Health Related Quality of Life (HRQoL) before and after treatment. |
| incidence of adverse events | All patients were assessed for adverse events every week during the first 4 weeks of treatment, and at 2-weeks interval for the following 5 months, and monthly thereafter. Adverse events were scaled according to CTCAE 5.0 | From the start of study treatment (Day 1) up to the end of Year 1 |
Countries
China
Contacts
Primary ContactXiaohui Zhang
Backup ContactQiusha Huang
Outcome results
None listed