A Safety and Efficacy Study of NAC in Patients With TA-TMA

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Safety and Efficacy Study of N-acetylcysteine in Patients With Transplant-Associated Thrombotic Microangiopathy

Conditions
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Thrombotic Microangiopathies, Hematologic Diseases

Intervention / Treatment
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* Drug: N-Acetylcysteine
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients be scheduled to undergo HSCT; Not received decitabine 6 month ago; Without severe organ damage; ECOG 0-2; Informed consent were obtained. Exclusion Criteria: Be sensitive to NAC; Bronchial asthma； Peptic ulcer； Severe organ damage； Pregnancy and breastfeeding women；
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental Group<br>N-Acetylcysteine | Drug: N-Acetylcysteine<br>* 50mg/Kg.d, oral<br>* Other names: NAC;|
| Placebo Comparator: Control Group<br>Placebo Oral Tablet | Drug: Placebo Oral Tablet<br>* 50mg/Kg.d, oral<br>* Other names: Placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Incidence of TA-TMA. | The incidence of TMA after HSCT. | 100 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Level of VWF Multimers | The level of VWF multimers in patients post HSCT. | 100 days | 
| The Level of Endothelial Micro Particle | The level of endothelial micro particle in patients post HSCT. | 100 days | 
| The Level of TNF-α | The level of TNF-α in patients post HSCT. | 40 days | 
| The Level of ROS | The level of ROS in patients post HSCT. | 100 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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N-acetylcysteine, Complement, Thrombotic Microangiopathies