Hematologic Diseases, Thrombotic Microangiopathies
Conditions
Keywords
N-acetylcysteine, Complement, Thrombotic Microangiopathies
Brief summary
HSCT associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen within 100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. N-Acetylcysteine (NAC) is a small, simple molecule that began as a generic drug almost 40 years ago. It has since been approved by the FDA for many indications. The investigators conducted an prospective clinical trial to evaluate the safety and efficiency of NAC in patients with TA-TMA.
Detailed description
Hematopoietic stem cell transplantation (HSCT) has been commonly used as a potentially curative option in the treatment of various hematological malignancies. However, it may end up with serious complications in various systems, including the hemostatic system. HSCT associated thrombotic microangiopathy(TA-TMA) is a heterogeneous, fatal disorder seen within 100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. Since the pathophysiology has not been clarified, there are no established treatments for TA-TMA several agents seem to have successful results. N-Acetylcysteine (NAC) is a small, simple molecule that began as a generic drug almost 40 years ago. It has since been approved by the FDA for many indications. Studies showed NAC reduce plasma VWF multimers and VWF multimeric size without an effect on the bleeding time in vitro and in vivo, thus proposed as a possible supplementary treatment for TTP. The investigators conducted an prospective clinical trial to evaluate the safety and efficiency of NAC in patients with TA-TMA.
Interventions
DRUGN-Acetylcysteine
50mg/Kg.d, oral
DRUGPlacebo Oral Tablet
50mg/Kg.d, oral
Sponsors
The First Affiliated Hospital of Soochow University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
1. Patients be scheduled to undergo HSCT; 2. Not received decitabine 6 month ago; 3. Without severe organ damage; 4. ECOG 0-2; 5. Informed consent were obtained.
Exclusion criteria
1. Be sensitive to NAC; 2. Bronchial asthma； 3. Peptic ulcer； 4. Severe organ damage； 5. Pregnancy and breastfeeding women；
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Incidence of TA-TMA. | 100 days | The incidence of TMA after HSCT. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The Level of VWF Multimers | 100 days | The level of VWF multimers in patients post HSCT. |
| The Level of Endothelial Micro Particle | 100 days | The level of endothelial micro particle in patients post HSCT. |
| The Level of TNF-α | 40 days | The level of TNF-α in patients post HSCT. |
| The Level of ROS | 100 days | The level of ROS in patients post HSCT. |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| NAC Group N-Acetylcysteine 50mg/Kg.d, oral | 66 |
| Placebo Group Placebo oral tablet 50mg/Kg.d, oral | 74 |
| Total | 140 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Lost to Follow-up | 6 | 6 |
| Overall Study | Protocol Violation | 6 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | NAC Group | Placebo Group | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 7 Participants | 11 Participants | 18 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 59 Participants | 63 Participants | 122 Participants |
| Primary Diseases Acute lymphoblastic leukemia | 15 Participants | 18 Participants | 33 Participants |
| Primary Diseases Acute myeloid leukemia | 39 Participants | 38 Participants | 77 Participants |
| Primary Diseases Aplastic anemia | 3 Participants | 5 Participants | 8 Participants |
| Primary Diseases Chronic myelogenous leukemia | 1 Participants | 2 Participants | 3 Participants |
| Primary Diseases Lymphoma and multiple myeloma | 1 Participants | 1 Participants | 2 Participants |
| Primary Diseases Myelodysplastic syndrome | 7 Participants | 10 Participants | 17 Participants |
| Race/Ethnicity, Customized Yellow Race | 66 Participants | 74 Participants | 140 Participants |
| Region of Enrollment China | 66 participants | 74 participants | 140 participants |
| Sex: Female, Male Female | 30 Participants | 38 Participants | 68 Participants |
| Sex: Female, Male Male | 36 Participants | 36 Participants | 72 Participants |
| Transplant Type HLA identical sibling | 14 Participants | 16 Participants | 30 Participants |
| Transplant Type Matched unrelated | 1 Participants | 3 Participants | 4 Participants |
| Transplant Type Related haplo-identical | 51 Participants | 55 Participants | 106 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 16 / 66 | 27 / 74 |
| other Total, other adverse events | 59 / 66 | 72 / 74 |
| serious Total, serious adverse events | 0 / 66 | 0 / 74 |
Outcome results
Primary
The Incidence of TA-TMA.
The incidence of TMA after HSCT.
Time frame: 100 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| NAC Group | The Incidence of TA-TMA. | 5 Participants |
| Placebo Group | The Incidence of TA-TMA. | 15 Participants |
Secondary
The Level of Endothelial Micro Particle
The level of endothelial micro particle in patients post HSCT.
Time frame: 100 days
Secondary
The Level of ROS
The level of ROS in patients post HSCT.
Time frame: 100 days
Secondary
The Level of TNF-α
The level of TNF-α in patients post HSCT.
Time frame: 40 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| NAC Group | The Level of TNF-α | 0.4 pg/mL |
| Placebo Group | The Level of TNF-α | 0.3 pg/mL |
Secondary
The Level of VWF Multimers
The level of VWF multimers in patients post HSCT.
Time frame: 100 days