The Efficiency and Safety of N-acetylcysteine for Prevention of Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation
Trial Snapshot
- Phase
- Phase 3
- Status
- Not yet recruiting
- Sponsor
- Enrollment
- 260
- Primary Endpoint
- The incidence of thrombotic disorders
Study Overview
Brief Summary
We aim to assess the the efficiency and safety of N-acetylcysteine for prevention of thrombotic events after allogenic hematopoietic stem cell transplantation.
Detailed Description
The thrombotic events are increasingly recognized complications of hematopoietic cell transplantation (HCT) associated with significant morbidity and mortality, which include transplantation-associated thrombotic microangiopathy (TA-TMA), sinusoidal obstructive syndrome (SOS), deep vein thrombosis (DVT), pulmonary thromboembolism (PTE), catheter-related thrombosis (CRT), superficial vein thrombosis (SVT), etc. There is a complex interplay on balancing the risk for thrombosis and bleeding in these patients, making treatment decisions particularly challenging. Emerging studies revealed that endothelial injury is the common underlying mechanism among different thrombotic disorders. There is increasing data that N-acetyl-cysteine (NAC) may prevent or improve endothelial dysfunction by inhibiting ROS production and preventing endothelial apoptosis. Our previous study showed low dose NAC could decrease the incidence of TA-TMA. In this study, we aim to assess the the efficiency and safety of N-acetylcysteine for prevention of thrombotic events after allogenic hematopoietic stem cell transplantation.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 16 Years to 70 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Aged 16-70 years old
- •Diagnosed as myeloid malignancies, and about to undergo allo-HSCT;
- •Expected survival longer than 1 month
Exclusion Criteria
- •Allergic to any components of NAC;
- •Severe dysfunction of heart, liver, lung and kidney;
- •Relapse before HSCT;
- •A history of bronchial asthma, bronchospasm or moderate / severe gastrohelcosis.
Arms & Interventions
Arm A
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion; N-acetyl-cysteine (Zambon Pharma, Hainan, China) : 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45.
Intervention: Cytarabine (Drug)
Arm A
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion; N-acetyl-cysteine (Zambon Pharma, Hainan, China) : 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45.
Intervention: N-acetyl-cysteine (Drug)
Arm A
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion; N-acetyl-cysteine (Zambon Pharma, Hainan, China) : 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45.
Intervention: Busulfan (Drug)
Arm A
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion; N-acetyl-cysteine (Zambon Pharma, Hainan, China) : 8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45.
Intervention: Cyclophosphamide (Drug)
Arm B
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion.
Intervention: Busulfan (Drug)
Arm B
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion.
Intervention: Cytarabine (Drug)
Arm B
Modified BUCY conditioning regimen: busulfan (3.2mg/kg, day-7 to day -5), cytarabine (2g/m2, day -8), cyclophosphamide (1.8g/m2, day -4 to day -3), followed by stem cells infusion.
Intervention: Cyclophosphamide (Drug)
Outcomes
Primary Outcomes
The incidence of thrombotic disorders
Time Frame: 1 year
The incidence of thrombotic disorders (TA-TMA, SOS, DVT, PTE, CRT, SVT) after allogenic hematopoietic stem cell transplantation
Overall survival
Time Frame: 1 year
The rate of overall survival after allogenic hematopoietic stem cell transplantation
Secondary Outcomes
- The incidence of GVHD(1 year)
- The incidence of relapse(1 year)
- The incidence of hematopoietic reconstitution(1 year)