The Use of N-acetylcysteine for Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation

Thrombotic Disorder Clinical Trial

Official title:

The Efficiency and Safety of N-acetylcysteine for Prevention of Thrombotic Events After Allogenic Hematopoietic Stem Cell Transplantation

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05907486
• Other study ID #: SOOCHOW-HY-2023-05-30
• Status: Not yet recruiting
• Phase: Phase 3
• Start date: August 1, 2023
• Est. completion date: December 1, 2025

Study information

• Verified date: May 2023
• Source: The First Affiliated Hospital of Soochow University
• Contact: Yaqiong Tang, Doctor
• Phone: 18896588075
• Email: tangyaqiong[@]suda.edu.cn
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

We aim to assess the the efficiency and safety of N-acetylcysteine for prevention of thrombotic events after allogenic hematopoietic stem cell transplantation.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 260
• Est. completion date: December 1, 2025
• Est. primary completion date: August 1, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Aged 16-70 years old

2. Diagnosed as myeloid malignancies, and about to undergo allo-HSCT;

3. ECOG: 0-2;

4. Expected survival longer than 1 month

Exclusion Criteria:

1. Allergic to any components of NAC;

2. Severe dysfunction of heart, liver, lung and kidney;

3. Relapse before HSCT;

4. A history of bronchial asthma, bronchospasm or moderate / severe gastrohelcosis.

Related Conditions & MeSH terms

• Thrombosis
• Thrombotic Disorder

Intervention

Drug:
• N-acetyl-cysteine
8g/d (>=45kg); 200mg/kg.d (<45kg), intravenously for at least 4 hours, day -9 to day +45
• Busulfan
3.2mg/kg, day-7 to day -5, intravenously
• Cytarabine
2g/m2, day -8, intravenously
• Cyclophosphamide
1.8g/m2, day -4 to day -3, intravenously

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
The First Affiliated Hospital of Soochow University

References & Publications (9)

Carreras E, Diaz-Beya M, Rosinol L, Martinez C, Fernandez-Aviles F, Rovira M. The incidence of veno-occlusive disease following allogeneic hematopoietic stem cell transplantation has diminished and the outcome improved over the last decade. Biol Blood Marrow Transplant. 2011 Nov;17(11):1713-20. doi: 10.1016/j.bbmt.2011.06.006. Epub 2011 Jun 25. — View Citation

Coppell JA, Richardson PG, Soiffer R, Martin PL, Kernan NA, Chen A, Guinan E, Vogelsang G, Krishnan A, Giralt S, Revta C, Carreau NA, Iacobelli M, Carreras E, Ruutu T, Barbui T, Antin JH, Niederwieser D. Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome. Biol Blood Marrow Transplant. 2010 Feb;16(2):157-68. doi: 10.1016/j.bbmt.2009.08.024. Epub 2009 Sep 18. — View Citation

George JN, Li X, McMinn JR, Terrell DR, Vesely SK, Selby GB. Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome following allogeneic HPC transplantation: a diagnostic dilemma. Transfusion. 2004 Feb;44(2):294-304. doi: 10.1111/j.1537-2995.2004.00700.x. — View Citation

Ho VT, Cutler C, Carter S, Martin P, Adams R, Horowitz M, Ferrara J, Soiffer R, Giralt S. Blood and marrow transplant clinical trials network toxicity committee consensus summary: thrombotic microangiopathy after hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 2005 Aug;11(8):571-5. doi: 10.1016/j.bbmt.2005.06.001. — View Citation

Jodele S, Laskin BL, Dandoy CE, Myers KC, El-Bietar J, Davies SM, Goebel J, Dixon BP. A new paradigm: Diagnosis and management of HSCT-associated thrombotic microangiopathy as multi-system endothelial injury. Blood Rev. 2015 May;29(3):191-204. doi: 10.1016/j.blre.2014.11.001. Epub 2014 Nov 28. — View Citation

Labrador J, Lopez-Anglada L, Perez-Lopez E, Lozano FS, Lopez-Corral L, Sanchez-Guijo FM, Vazquez L, Perez Rivera JA, Martin-Herrero F, Sanchez-Barba M, Guerrero C, del Canizo MC, Caballero MD, San Miguel JF, Alberca I, Gonzalez-Porras JR. Analysis of incidence, risk factors and clinical outcome of thromboembolic and bleeding events in 431 allogeneic hematopoietic stem cell transplantation recipients. Haematologica. 2013 Mar;98(3):437-43. doi: 10.3324/haematol.2012.069559. Epub 2012 Aug 16. — View Citation

Laskin BL, Goebel J, Davies SM, Jodele S. Small vessels, big trouble in the kidneys and beyond: hematopoietic stem cell transplantation-associated thrombotic microangiopathy. Blood. 2011 Aug 11;118(6):1452-62. doi: 10.1182/blood-2011-02-321315. Epub 2011 May 19. — View Citation

Sartain S, Shubert S, Wu MF, Srivaths P, Teruya J, Krance R, Martinez C. Therapeutic Plasma Exchange does not Improve Renal Function in Hematopoietic Stem Cell Transplantation-Associated Thrombotic Microangiopathy: An Institutional Experience. Biol Blood Marrow Transplant. 2019 Jan;25(1):157-162. doi: 10.1016/j.bbmt.2018.08.016. Epub 2018 Aug 23. — View Citation

Tsirigotis PD, Resnick IB, Avni B, Grisariu S, Stepensky P, Or R, Shapira MY. Incidence and risk factors for moderate-to-severe veno-occlusive disease of the liver after allogeneic stem cell transplantation using a reduced intensity conditioning regimen. Bone Marrow Transplant. 2014 Nov;49(11):1389-92. doi: 10.1038/bmt.2014.168. Epub 2014 Jul 28. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The incidence of thrombotic disorders	The incidence of thrombotic disorders (TA-TMA, SOS, DVT, PTE, CRT, SVT) after allogenic hematopoietic stem cell transplantation	1 year
Primary	Overall survival	The rate of overall survival after allogenic hematopoietic stem cell transplantation	1 year
Secondary	The incidence of relapse	The incidence of relapse after allogenic hematopoietic stem cell transplantation	1 year
Secondary	The incidence of GVHD	The incidence of GVHD after allogenic hematopoietic stem cell transplantation	1 year
Secondary	The incidence of hematopoietic reconstitution	The incidence of hematopoietic reconstitution after allogenic hematopoietic stem cell transplantation	1 year