Clinical trial NCT03252925: A Safety and Efficacy Study of NAC in Patients With TA-TMA
Official title: A Safety and Efficacy Study of N-acetylcysteine in Patients With Transplant-Associated Thrombotic Microangiopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thrombotic Microangiopathies
Hematologic Diseases
Keywords: N-acetylcysteine
Complement
Thrombotic Microangiopathies
Lead sponsor: The First Affiliated Hospital of Soochow University
Sponsor class: OTHER
First posted: 2017-08-17
Enrollment: 170
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility criteria: 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；

Primary outcomes:
measure: The Incidence of TA-TMA.
timeFrame: 100 days
Secondary outcomes:
measure: The Level of VWF Multimers
timeFrame: 100 days
measure: The Level of Endothelial Micro Particle
timeFrame: 100 days
measure: The Level of TNF-α
timeFrame: 40 days
measure: The Level of ROS
timeFrame: 100 days
Other outcomes:
Locations:
city: Suzhou
country: China
facility: The First affiliated Hospital of SooChow University
state: Jiangsu
Study officials:
affiliation: The First Affiliated Hospital of Soochow University
name: Depei Wu, MD. PhD.
role: STUDY_CHAIR
References:
citation: George JN, Lopez JA, Konkle BA. N-Acetylcysteine: an old drug, a new insight, a potentially effective treatment for thrombotic thrombocytopenic purpura. Transfusion. 2014 May;54(5):1205-7. doi: 10.1111/trf.12561. No abstract available.
citation: Tersteeg C, Roodt J, Van Rensburg WJ, Dekimpe C, Vandeputte N, Pareyn I, Vandenbulcke A, Plaimauer B, Lamprecht S, Deckmyn H, Lopez JA, De Meyer SF, Vanhoorelbeke K. N-acetylcysteine in preclinical mouse and baboon models of thrombotic thrombocytopenic purpura. Blood. 2017 Feb 23;129(8):1030-1038. doi: 10.1182/blood-2016-09-738856. Epub 2016 Dec 23.
citation: Acedillo RR, Govind M, Kashgary A, Clark WF. Treatment of severe, refractory and rapidly evolving thrombotic thrombocytopenic purpura. BMJ Case Rep. 2016 Jun 9;2016:bcr2016215491. doi: 10.1136/bcr-2016-215491.
citation: Rottenstreich A, Hochberg-Klein S, Rund D, Kalish Y. The role of N-acetylcysteine in the treatment of thrombotic thrombocytopenic purpura. J Thromb Thrombolysis. 2016 May;41(4):678-83. doi: 10.1007/s11239-015-1259-6.