Immune Thrombocytopenic Purpura
Conditions
Keywords
immune thrombocytopenia, atorvastatin, N-acetyl-L-cysteine, romiplostim, sustained response off-treatment
Brief summary
This is a prospective, single-arm, open-lable, single-center study and we aimed to determine whether atorvastatin combined with N-acetyl-L-cysteine (NAC) plus romiplostim could induce sustained response off-treatment (SRoT) in adult patients with ITP following CS failure.
Detailed description
This is a prospective, single-arm trial designed to investigate whether atorvastatin combined with N-acetyl-L-cysteine (NAC) plus romiplostim can induce a sustained response off-treatment (SRoT) in adult patients with immune thrombocytopenia (ITP) who experienced failure of first-line corticosteroid therapy. In this study, SRoT is defined as an off-treatment period during which the platelet count remains above 30×10⁹/L in the absence of bleeding events or rescue therapy. The primary endpoint was the proportion of patients who achieved SRoT by Week 24 after the discontinuation of romiplostim. From Week 1 to Week 24, atorvastatin and NAC was administrated as the dose of 20mg qd and 400mg tid,respectively, and were discontinued at the end of Week 24. During the initial 24 weeks, romiplostim was initiated at a starting dose of 3 μg/kg per week. The weekly dose was adjusted based on platelet counts, with a maximum dose of 10 μg/kg per week, to maintain platelet levels within the range of 100-200×10⁹/L. From Week 25 to Week 35, romiplostim was gradually tapered and discontinued, with the goal of maintaining a platelet count ≥30×10⁹/L and no less than twice the baseline level. After all medications (including atorvastatin, NAC, and romiplostim) were discontinued (no later than Week 36), patients were followed up for an additional 24 weeks to evaluate the sustained response rate at 24 weeks post-treatment cessation.
Interventions
DRUGatorvastatin, NAC, and romiplostim
From Week 1 to Week 24, atorvastatin and NAC was administrated as the dose of 20mg qd and 400mg tid,respectively, and were discontinued at the end of Week 24. For romiplostim, the initial dose was 3 μg/kg per week. The weekly dose was adjusted based on platelet counts, with a maximum dose of 10 μg/kg per week, to maintain platelet levels within the range of 100-200×10⁹/L during the initial 24-week period. From Week 25 to Week 35, romiplostim was gradually tapered and discontinued with the goal of maintaining a platelet count ≥30×10⁹/L and no less than twice the baseline level. After all medications (including atorvastatin, NAC, and romiplostim) were discontinued (no later than Week 36), patients were followed up for an additional 24 weeks to evaluate the sustained response rate at 24 weeks post-treatment cessation.
Sponsors
Peking University People's Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with primary ITP; * Aged ≥18 years; * Patients with treatment failure or relapse after first-line corticosteriod therapy for ITP; * Platelet count \<30×10⁹/L.
Exclusion criteria
* Pregnant or lactating women, and who were possibly pregnant, planning to become pregnant, or who had partners planning to become pregnant; * Presence of active malignant tumors; * Active HBV, HCV or HIV infection; * Active infection requiring systematic treatment; * Leukemia, myelodysplastic syndrome, aplastic anemia, myelofibrosis or other hematological disorders that may cause thrombocytopenia; * History or presence of myocardial infarction, unstable ischemic heart disease, stroke, or NYHA Class IV heart failure; * AST \> 2 times the upper limit of normal (ULN), ALT \> 2×ULN, or TBIL ≥ 1.5×ULN; * eGFR \< 50 mL/min/1.73m²; * Any other subjects deemed ineligible for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 24-week SRoT rate | 24 weeks post-treatment cessation | Sustained response off-treatment (SRoT) rate is defined as the proportion of patients who maintain a platelet count ≥30×10\^9/L and at least a two-fold increase from the baseline count without active bleeding following treatment discontinuation. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 24-week SCRoT rate | 24 weeks after treatment discontinuation | Sustained complete response off-treatment (SCRoT) rate was defined as the proportion of patients who maintain a platelet count of ≥100×10⁹/L without active bleeding after treatment discontinuation. |
| ORR | Up to the end of week 24 | Overall response rate (ORR) is defined as the proportion of patients who achieve platelet count ≥30×10\^9/L and more than twice the baseline level, with no signs of active bleeding. |
| CR rate | Up to the end of week 24 | Complete response (CR) rate is defined as the proportion of patients who achieve a platelet count ≥100×10⁹/L with no signs of active bleeding. |
| TTR | Up to the end of week 24 | Time to response (TTR) is defined as the days from treatment initiation to first platete count reaching ≥30×10\^9/L |
| Sustained response | Up to the end of week 24 | Platelet count ≥30×10⁹/L and at least doubled from baseline on at least three of four scheduled visits during the final 8 weeks of the initial 24-week treatment phase without active bleeding. |
| Bleeding events | Up to the end of week 24; Week 25 to 24 weeks post-treatment cessation | Bleeding incidence and severity per WHO bleeding score |
| Adverse Events | Up to the end of week 24; Week 25 to 24 weeks post-treatment cessation | The proportion of patients with adverse events |
Countries
China
Contacts
CONTACTFu Haixia, Dr.
CONTACTXiaohui Zhang, Dr.
Outcome results
None listed