A Safety and Efficacy Study of NAC in Patients With TA-TMA
Study Details
Study Description
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.
Condition or Disease | Intervention/Treatment | Phase |
---|---|---|
|
Phase 3 |
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.
Study Design
Arms and Interventions
Arm | Intervention/Treatment |
---|---|
Experimental: Experimental Group N-Acetylcysteine |
Drug: N-Acetylcysteine
50mg/Kg.d, oral
Other Names:
|
Placebo Comparator: Control Group Placebo Oral Tablet |
Drug: Placebo Oral Tablet
50mg/Kg.d, oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- The Incidence of TA-TMA. [100 days]
The incidence of TMA after HSCT.
Secondary Outcome Measures
- 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.
Eligibility Criteria
Criteria
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;
Contacts and Locations
Locations
Site | City | State | Country | Postal Code | |
---|---|---|---|---|---|
1 | The First affiliated Hospital of SooChow University | Suzhou | Jiangsu | China | 215006 |
Sponsors and Collaborators
- The First Affiliated Hospital of Soochow University
Investigators
- Study Chair: Depei Wu, MD. PhD., The First Affiliated Hospital of Soochow University
Study Documents (Full-Text)
More Information
Publications
- 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. pii: bcr2016215491. doi: 10.1136/bcr-2016-215491.
- George JN, López 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.
- 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.
- 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.
- SOOCHOW-HY-2017
Study Results
Participant Flow
Recruitment Details | |
---|---|
Pre-assignment Detail |
Arm/Group Title | Experimental Group | Control Group |
---|---|---|
Arm/Group Description | N-Acetylcysteine N-Acetylcysteine: 50mg/Kg.d, oral | Placebo Oral Tablet Placebo Oral Tablet: 50mg/Kg.d, oral |
Period Title: Overall Study | ||
STARTED | 80 | 80 |
COMPLETED | 66 | 74 |
NOT COMPLETED | 14 | 6 |
Baseline Characteristics
Arm/Group Title | NAC Group | Placebo Group | Total |
---|---|---|---|
Arm/Group Description | N-Acetylcysteine 50mg/Kg.d, oral | Placebo oral tablet 50mg/Kg.d, oral | Total of all reporting groups |
Overall Participants | 66 | 74 | 140 |
Age (Count of Participants) | |||
<=18 years |
7
10.6%
|
11
14.9%
|
18
12.9%
|
Between 18 and 65 years |
59
89.4%
|
63
85.1%
|
122
87.1%
|
>=65 years |
0
0%
|
0
0%
|
0
0%
|
Sex: Female, Male (Count of Participants) | |||
Female |
30
45.5%
|
38
51.4%
|
68
48.6%
|
Male |
36
54.5%
|
36
48.6%
|
72
51.4%
|
Race/Ethnicity, Customized (Count of Participants) | |||
Yellow Race |
66
100%
|
74
100%
|
140
100%
|
Region of Enrollment (participants) [Number] | |||
China |
66
100%
|
74
100%
|
140
100%
|
Primary Diseases (Count of Participants) | |||
Acute myeloid leukemia |
39
59.1%
|
38
51.4%
|
77
55%
|
Acute lymphoblastic leukemia |
15
22.7%
|
18
24.3%
|
33
23.6%
|
Aplastic anemia |
3
4.5%
|
5
6.8%
|
8
5.7%
|
Chronic myelogenous leukemia |
1
1.5%
|
2
2.7%
|
3
2.1%
|
Myelodysplastic syndrome |
7
10.6%
|
10
13.5%
|
17
12.1%
|
Lymphoma and multiple myeloma |
1
1.5%
|
1
1.4%
|
2
1.4%
|
Transplant Type (Count of Participants) | |||
HLA identical sibling |
14
21.2%
|
16
21.6%
|
30
21.4%
|
Related haplo-identical |
51
77.3%
|
55
74.3%
|
106
75.7%
|
Matched unrelated |
1
1.5%
|
3
4.1%
|
4
2.9%
|
Outcome Measures
Title | The Incidence of TA-TMA. |
---|---|
Description | The incidence of TMA after HSCT. |
Time Frame | 100 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | NAC Group | Placebo Group |
---|---|---|
Arm/Group Description | N-Acetylcysteine 50mg/Kg.d, oral | Placebo Oral Tablet 50mg/Kg.d, oral |
Measure Participants | 66 | 77 |
Count of Participants [Participants] |
5
7.6%
|
15
20.3%
|
Title | The Level of VWF Multimers |
---|---|
Description | The level of VWF multimers in patients post HSCT. |
Time Frame | 100 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | The Level of Endothelial Micro Particle |
---|---|
Description | The level of endothelial micro particle in patients post HSCT. |
Time Frame | 100 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Title | The Level of TNF-α |
---|---|
Description | The level of TNF-α in patients post HSCT. |
Time Frame | 40 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title | NAC Group | Placebo Group |
---|---|---|
Arm/Group Description | N-Acetylcysteine 50mg/Kg.d, oral | Placebo Oral Tablet 50mg/Kg.d, oral |
Measure Participants | 66 | 74 |
Median (Inter-Quartile Range) [pg/mL] |
0.4
|
0.3
|
Title | The Level of ROS |
---|---|
Description | The level of ROS in patients post HSCT. |
Time Frame | 100 days |
Outcome Measure Data
Analysis Population Description |
---|
[Not Specified] |
Arm/Group Title |
---|
Arm/Group Description |
Adverse Events
Time Frame | 100 days | |||
---|---|---|---|---|
Adverse Event Reporting Description | ||||
Arm/Group Title | NAC Group | Placebo | ||
Arm/Group Description | N-Acetylcysteine 50mg/Kg.d, oral | Placebo Oral Tablet 50mg/Kg.d, oral | ||
All Cause Mortality |
||||
NAC Group | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 16/66 (24.2%) | 27/74 (36.5%) | ||
Serious Adverse Events |
||||
NAC Group | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 0/66 (0%) | 0/74 (0%) | ||
Other (Not Including Serious) Adverse Events |
||||
NAC Group | Placebo | |||
Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
Total | 59/66 (89.4%) | 72/74 (97.3%) | ||
Blood and lymphatic system disorders | ||||
Fever | 20/66 (30.3%) | 37/74 (50%) | ||
Erythra | 11/66 (16.7%) | 15/74 (20.3%) | ||
Gastrointestinal disorders | ||||
Abdominal pain or diarrhea | 36/66 (54.5%) | 49/74 (66.2%) | ||
Upper gastrointestinal complications | 3/66 (4.5%) | 18/74 (24.3%) | ||
Gastrointestinal bleeding | 6/66 (9.1%) | 6/74 (8.1%) | ||
Nervous system disorders | ||||
Epilepsy | 1/66 (1.5%) | 4/74 (5.4%) | ||
Renal and urinary disorders | ||||
Hemorrhagic cystitis | 27/66 (40.9%) | 43/74 (58.1%) | ||
Respiratory, thoracic and mediastinal disorders | ||||
Cough or expectoration | 9/66 (13.6%) | 15/74 (20.3%) | ||
Chest tightness | 2/66 (3%) | 5/74 (6.8%) | ||
Vascular disorders | ||||
Dizziness or headache | 5/66 (7.6%) | 12/74 (16.2%) |
Limitations/Caveats
More Information
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title | Yue Han |
---|---|
Organization | The First Affiliated Hospital of Soochow University |
Phone | 13901551669 |
hanyue@suda.edu.cn |
- SOOCHOW-HY-2017