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

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.

• N-Acetylcysteine (Drug), also known as NAC: 50mg/Kg.d, oral
• Placebo Oral Tablet (Drug), also known as Placebo: 50mg/Kg.d, oral

Primary outcomes

• The Incidence of TA-TMA. [100 days]: The incidence of TMA after HSCT.

Secondary outcomes

• 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.

Sex: All

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；

Participant flow

Outcome results

• The Incidence of TA-TMA. (Primary), Count of participants, Participants: NAC Group 5; Placebo Group 15
• The Level of VWF Multimers (Secondary)
• The Level of Endothelial Micro Particle (Secondary)
• The Level of TNF-α (Secondary), Median, pg/mL: NAC Group 0.4 (0 to 1.4); Placebo Group 0.3 (0 to 2.1)
• The Level of ROS (Secondary)

Adverse events

Time frame: 100 days

Other adverse events by term

Limitations and caveats: Several outcome indicators are entirely inconsistent with our study's actual course of execution. First, the occurrence of TA-TMA was not limited to the first 100 days after hematopoietic stem cell transplantation. Secondly, the detection of VWF multimers, endothelial microparticles, and ROS was not performed according to the protocol.

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• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2017-11-01)

• Depei Wu, MD. PhD., Study chair, The First Affiliated Hospital of Soochow University