N-Acetylcysteine as Therapy for Transplantation- Associated Thrombotic Microangiopathy

NCT07279610 | Active Not Recruiting Phase 2 DMC

• 1 other identifier: SOOCHOW-HY-2024
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

This multicenter, prospective, single-arm clinical trial aims to evaluate the efficacy and safety of N-acetylcysteine (NAC) for treating Transplantation-Associated Thrombotic Microangiopathy (TA-TMA), a severe complication of hematopoietic stem cell transplantation characterized by microangiopathic hemolytic anemia, thrombocytopenia, and organ injury, with an incidence of 4%-30%. Current treatments, including plasma exchange (response rate \<10%) and costly complement inhibitors like Eculizumab (71% response) which are not widely accessible, are inadequate. Inspired by NAC's success in treating the related condition thrombotic thrombocytopenic purpura (TTP) and supported by bioinformatic analyses of patient data revealing enhanced oxidative stress pathways and identifying NAC as a potential targeted therapy, our prior study demonstrated that NAC prophylaxis significantly reduces TA-TMA incidence and improves survival. Building on this promising foundation, this study will enroll patients meeting TA-TMA diagnostic criteria for NAC treatment, assessing its potential as a safe, effective, and affordable therapeutic option.

Conditions

Thrombotic Microangiopathy

Outcome Measures

Primary Outcomes (1)

• The efficacy of N-acetylcysteine treatment for TA-TMA

  Evaluate the efficacy of N-acetylcysteine in patients with TA-TMA by response defined as: 1. Improvement in TMA laboratory markers of platelet count and lactate dehydrogenase (LDH), and 2. Improvement in clinical status

  Day 1 to 60 days after the enrollment of N-acetylcysteine

Secondary Outcomes (9)

• 100-day survival

  Study Day of TA-TMA diagnosis to 100 days later

• Platelet count change from baseline

  Study Day 1 to Day 60

• Change From Baseline in LDH

  Study Day 1 to Day 60

• Change From Baseline in Hemoglobin

  Study Day 1 to Day 60

• Change From Baseline in Creatine

  Study Day 1 to Day 60

Study Arms (1)

NAC

EXPERIMENTAL

N-acetylcysteine injection will be administered intravenously to TA-TMA patients at a total daily dose of 16g. The daily dose is divided into two equal doses of 8g each, administered in the morning and evening. Each 8g dose is to be infused over a period of 1 hour. This regimen continues for 14 consecutive days.

Drug: N-Acetylcysteine (NAC) Treatment

Interventions

N-Acetylcysteine (NAC) Treatment DRUG

N-acetylcysteine injection will be administered intravenously to TA-TMA patients at a total daily dose of 16g. The daily dose is divided into two equal doses of 8g each, administered in the morning and evening. Each 8g dose is to be infused over a period of 1 hour. This regimen continues for 14 consecutive days.

NAC

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 1. Informed Consent: The patient must have the ability to understand and the willingness to participate in the study and must sign a written Informed Consent Form.
• \. Age: ≥ 18 years old, regardless of gender. 3. Diagnosis: Subjects diagnosed with TA-TMA according to the Harmonizing Definitions, defined as meeting one of the following:
• TA-TMA confirmed by renal or intestinal biopsy, OR
• Fulfilling at least four of the following seven clinical or laboratory criteria within a 14-day period:
• Anemia, defined as persistent transfusion dependence after myeloid engraftment, OR a decrease in hemoglobin \>10 g/L, OR new-onset transfusion dependence.
• Thrombocytopenia, defined as failure of platelet engraftment, OR a higher-than-expected platelet transfusion requirement, OR refractory platelet transfusion, OR a \>50% decrease in platelets after initial engraftment.
• Lactate dehydrogenase (LDH) level above the upper limit of normal (ULN).
• Presence of schistocytes on peripheral blood smear.
• Hypertension (blood pressure ≥140/90 mmHg).
• sC5b-9 level above the ULN.
• Proteinuria (random urine protein-to-creatinine ratio ≥1 mg/mg).

You may not qualify if:

• \. The subject has received complement blockade therapy (e.g., Eculizumab or Narsoplimab) within the past 3 months.
• \. The subject has a history of drug and/or alcohol abuse within the 6 months prior to enrollment.
• \. The subject has a life expectancy of less than 3 months. 4. The subject is considered by the investigator to be unable or unwilling to cooperate with the study procedures.
• \. The subject is a family member or employee of the investigator. 6. The patient is pregnant or lactating. 7. The subject has a history of Human Immunodeficiency Virus (HIV) infection. 8. The subject has a known allergy to any component of the investigational drug (N-acetylcysteine).
• \. The subject has cardiac insufficiency, defined as an ejection fraction (EF) \<30%, or NYHA Class III or higher heart failure, or other cardiac conditions deemed by the investigator as unsuitable for enrollment.
• \. The subject has contraindications to N-acetylcysteine, such as active bronchial asthma or peptic ulcer disease.
• \. The patient refuses to participate in the study.

Sponsors & Collaborators

• The First Affiliated Hospital of Soochow University: lead

Study Sites (1)

The First Affiliated Hospital of Soochow University

Suzhou, China

Location

Related Publications (6)

• Pan T, Qi J, Tang Y, Yao Y, Chen J, Wang H, Yang J, Xu X, Shi Q, Liu Y, He X, Chen F, Ma X, Hu X, Wu X, Wu D, Han Y. N-Acetylcysteine as Prophylactic Therapy for Transplantation-Associated Thrombotic Microangiopathy: A Randomized, Placebo-Controlled Trial. Transplant Cell Ther. 2022 Nov;28(11):764.e1-764.e7. doi: 10.1016/j.jtct.2022.07.029. Epub 2022 Aug 5.

  PMID: 35940529 RESULT

• Qi J, Hu S, He X, Pan T, Yang L, Zhang R, Tang Y, Wu D, Han Y. N-Acetyl-L-Cysteine Potentially Inhibits Complement Activation in Transplantation-Associated Thrombotic Microangiopathy. Transplant Cell Ther. 2022 Apr;28(4):216.e1-216.e5. doi: 10.1016/j.jtct.2021.12.018. Epub 2021 Dec 31.

  PMID: 34979328 RESULT

• 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.

  PMID: 28011677 RESULT

• Chen J, Reheman A, Gushiken FC, Nolasco L, Fu X, Moake JL, Ni H, Lopez JA. N-acetylcysteine reduces the size and activity of von Willebrand factor in human plasma and mice. J Clin Invest. 2011 Feb;121(2):593-603. doi: 10.1172/JCI41062. Epub 2011 Jan 25.

  PMID: 21266777 RESULT

• Zhang R, Zhou M, Qi J, Miao W, Zhang Z, Wu D, Han Y. Efficacy and Safety of Eculizumab in the Treatment of Transplant-Associated Thrombotic Microangiopathy: A Systematic Review and Meta-Analysis. Front Immunol. 2021 Jan 20;11:564647. doi: 10.3389/fimmu.2020.564647. eCollection 2020.

  PMID: 33552043 RESULT

• Schoettler ML, Carreras E, Cho B, Dandoy CE, Ho VT, Jodele S, Moissev I, Sanchez-Ortega I, Srivastava A, Atsuta Y, Carpenter P, Koreth J, Kroger N, Ljungman P, Page K, Popat U, Shaw BE, Sureda A, Soiffer R, Vasu S. Harmonizing Definitions for Diagnostic Criteria and Prognostic Assessment of Transplantation-Associated Thrombotic Microangiopathy: A Report on Behalf of the European Society for Blood and Marrow Transplantation, American Society for Transplantation and Cellular Therapy, Asia-Pacific Blood and Marrow Transplantation Group, and Center for International Blood and Marrow Transplant Research. Transplant Cell Ther. 2023 Mar;29(3):151-163. doi: 10.1016/j.jtct.2022.11.015. Epub 2022 Nov 25.

  PMID: 36442770 RESULT

MeSH Terms

Conditions

Thrombotic Microangiopathies

Interventions

Acetylcysteine; Therapeutics

Condition Hierarchy (Ancestors)

Thrombocytopenia; Blood Platelet Disorders; Hematologic Diseases; Hemic and Lymphatic Diseases; Cytopenia

Intervention Hierarchy (Ancestors)

Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 1, 2025
• First Posted: December 12, 2025
• Study Start: May 1, 2024
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: December 12, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)