Immune Thrombocytopenia
Conditions
Keywords
Immune thrombocytopenia;, Corticosteriod resistance resistant/relaped, ATRA
Brief summary
A multicenter, randomized, double-blind placebo-controlled study to report the efficacy and safety of all-trans etinoic acid compared to placebo for the treatment of adults with corticosteriod-resistant/relapsed primary immune thrombocytopenia (ITP).
Detailed description
The investigators are undertaking a parallel-group, multicenter, randomized controlled trial of 192 adults with corticosteriod-resistant/relapsed primary ITP. Patients were randomized to all-trans etinoic acid and placebo group. Platelet count, bleeding, and other symptoms were evaluated before and after treatment. Adverse events are also recorded throughout the study.
Interventions
10mg twice daily ×24 weeks
DRUGPlacebo
10mg twice daily ×24 weeks
Sponsors
Peking University People's Hospital
Peking University First Hospital
Beijing Friendship Hospital
Beijing Tongren Hospital
Peking University Third Hospital
Beijing Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Primary ITP if aged ⩾18 years; * With an average of two platelet counts ⩾1 day apart of \<30×10\^9/L during screening and no single platelet count \>35×10\^9/L within 2 weeks before study treatment; * Patients who have previously received at least one first-line standard therapy for ITP (corticosteroid and/or intravenous immunoglobulin) with unsustained efficacy, relapse, intolerance to standard therapy, or insufficient response.
Exclusion criteria
* Pregnant or lactating women, and who were possibly pregnant, planning to become pregnant, or who had partners planning to become pregnant; * With active malignancy or a history of malignant tumor; * Having experienced severe bacterial, viral, fungal or parasitic infection within the past 4 weeks; * With a history of symptomatic herpes zoster infection within 12 weeks prior to screening; * Active or chronic HBV, HCV or HIV infection; * Evidence of active tuberculosis; or previous evidence of active tuberculosis without appropriate and documented treatment; or household contact with patients with active tuberculosis without appropriate and documented tuberculosis prophylaxis; * Receipt of live vaccines within the past 12 weeks, or planned live vaccination during the study period; * Prior ATRA therapy; * History of solid organ transplant or planned surgery; * Myelodysplastic syndrome, aplastic anemia or myelofibrosis; * Patients with other diseases were undergoing treatment with immunosuppressants; * Clinically significant thromboembolic events within the past 24 weeks, or ongoing anticoagulant treatment, who are deemed ineligible for the study by the investigator; * History or presence of myocardial infarction, unstable ischemic heart disease, stroke, or NYHA Class IV heart failure; * History or presence of cardiovascular, respiratory, hepatic, gastrointestinal, endocrine, neurological, neuropsychiatric or any other severe and/or unstable diseases that, in the opinion of the investigator, may pose an unacceptable risk with the investigational product or interfere with the interpretation of study data; * AST \> 2 times the upper limit of normal (ULN), ALT \> 2×ULN, TBIL ≥ 1.5×ULN; * WBC \< 2500/µL, neutrophil count \< 1200/µL, lymphocyte count \< 750/µL, hemoglobin \< 9 g/dL; * eGFR \< 50 mL/min/1.73m²; * Other patients deemed unsuitable for enrollment in this study by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Durable platelet response | Up to week 24 | Platelet count of ⩾50 × 10\^9/L or between ⩾30 × 10\^9/L and \<50 × 10\^9/L and at least doubled from baseline on at least four of six scheduled visits between weeks 14 and 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-week overall response rate | Up to week 24 | From enrollment to the end of week 24, the proportion of patients with at least one platelet count of ≥50×10⁹/L or between 30 × 10\^9/L and 50 × 10\^9/L plus at least doubled from baseline |
| 12-week overall response rate | Up to week 12 | From enrollment to the end of week 12, the proportion of patients with at least one platelet count of ≥50×10⁹/L or between 30 × 10\^9/L and 50 × 10\^9/L plus at least doubled from baseline |
| Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 30×10^9/L) | Up to week 24 | The proportion of participants who achieved platelet counts ≥ 30×10\^9/L and at least doubled from baseline at two consecutive visits |
| Consecutive Increased Platelet Counts (≥2 Consecutive PLT ≥ 50×10^9/L) | Up to week 24 | The proportion of patients with two consecutive platelet counts of 50×10⁹/L or more and doubling from the baseline count |
| Quality of Life Score | Up to week 24 | ITP-patient assessment questionnaire (ITP-PAQ) was used to assess the HRQoL before and after treatment. |
| Adverse Events | Up to week 28 | The rate of participants with adverse events |
| Complete response rate | Up to week 24 | The proportion of patients with a platelet count of ≥ 100×10\^9/L in absence of bleeding at any time |
| Duration of response | Up to 24 weeks | Number of weeks with platelet count of ≥50 × 10\^9/L or between 30 × 10\^9/L and 50 × 10\^9/L plus at least doubled from baseline |
| Time to response | Up to week 24 | Time from treatment initiation to first platelet count reaching ≥30x10\^9/L and doubling from the baseline count in 0-24 weeks |
| Initial response | Up to week 4 | Platelet count ≥30×10\^9/L and at least doubling baseline at day 28 |
| Peak platelet count | Up to week 24 | The peak platelet count without rescue treatment |
| Bleeding events | 0-12 weeks and 0-24 weeks | Bleeding incidence and severity per WHO bleeding score in 0-12 weeks and 0-24 weeks |
| Rescue treatment | Up to week 24 | Proportion of patients receiving predefined rescue treatment |
| Reduced or discontinued concomitant therapy | Up to week 24 | Proportion of patients with reduced or discontinued baseline concomitant anti-ITP therapy |
Countries
China
Contacts
CONTACTXiaohui Zhang, Prof.
CONTACTHaixia Fu, Dr.
Outcome results
None listed