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

Sponsor
The First Affiliated Hospital of Soochow University (Other)
Overall Status
Completed
CT.gov ID
NCT03252925
Collaborator
(none)
170
1
2
47
3.6

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

Study Type:
Interventional
Actual Enrollment :
170 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Prevention
Official Title:
A Safety and Efficacy Study of N-acetylcysteine in Patients With Transplant-Associated Thrombotic Microangiopathy
Actual Study Start Date :
Nov 1, 2017
Actual Primary Completion Date :
Oct 1, 2021
Actual Study Completion Date :
Oct 1, 2021

Arms and Interventions

Arm Intervention/Treatment
Experimental: Experimental Group

N-Acetylcysteine

Drug: N-Acetylcysteine
50mg/Kg.d, oral
Other Names:
  • NAC
  • Placebo Comparator: Control Group

    Placebo Oral Tablet

    Drug: Placebo Oral Tablet
    50mg/Kg.d, oral
    Other Names:
  • Placebo
  • Outcome Measures

    Primary Outcome Measures

    1. The Incidence of TA-TMA. [100 days]

      The incidence of TMA after HSCT.

    Secondary Outcome Measures

    1. The Level of VWF Multimers [100 days]

      The level of VWF multimers in patients post HSCT.

    2. The Level of Endothelial Micro Particle [100 days]

      The level of endothelial micro particle in patients post HSCT.

    3. The Level of TNF-α [40 days]

      The level of TNF-α in patients post HSCT.

    4. The Level of ROS [100 days]

      The level of ROS in patients post HSCT.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    N/A and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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;

    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

    Responsible Party:
    The First Affiliated Hospital of Soochow University
    ClinicalTrials.gov Identifier:
    NCT03252925
    Other Study ID Numbers:
    • SOOCHOW-HY-2017
    First Posted:
    Aug 17, 2017
    Last Update Posted:
    Feb 14, 2022
    Last Verified:
    Dec 1, 2021
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by The First Affiliated Hospital of Soochow University
    Additional relevant MeSH terms:

    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

    1. Primary Outcome
    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%
    2. Secondary Outcome
    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
    3. Secondary Outcome
    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
    4. Secondary Outcome
    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
    5. Secondary Outcome
    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

    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.

    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
    Email hanyue@suda.edu.cn
    Responsible Party:
    The First Affiliated Hospital of Soochow University
    ClinicalTrials.gov Identifier:
    NCT03252925
    Other Study ID Numbers:
    • SOOCHOW-HY-2017
    First Posted:
    Aug 17, 2017
    Last Update Posted:
    Feb 14, 2022
    Last Verified:
    Dec 1, 2021