Efficacy of N-acetylcysteine Versus Placebo as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation

Study Overview
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Brief Summary
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Sinusoidal obstruction syndrome (SOS) or hepatic veno-occlusive disease (VOD) is a serious complication that occurs, most often occurring in patients undergoing hematopoietic stem cell transplantation (HSCT), especially in its first thirty days. The morbidity and mortality in this syndrome are considerable, since severe SOS is associated with a mortality of more than 90% in the first hundred days of HSCT. Some risk factors are modifiable, especially those related to transplantation, but when non-alterable factors are present, preventive measures are needed that can reduce the incidence and / or severity of SOS.

Detailed Description
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This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine as prophylaxis of sinusoidal obstruction syndrome in patients undergoing hematopoietic stem cell transplantation Up to date, no approved medications are available for prophylactic treatment of sinusoidal obstruction syndrome in patients undergoing hematopoietic stem cell transplantation. N-acetylcysteine is a drug that has been long used as a mucolytic. And placebo responses contribute to help assess the appropriateness of randomized clinical trials in determining the size of drug effect. The study will enroll patients undergoing hematopoietic stem cell transplantation to receive sequentially one of two treatment: N-acetylcysteine or Placebo.

Official Title
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Prospective, Randomized Study Using N-Acetylcysteine as Prophylaxis of Sinusoidal Obstruction Syndrome in Patients Undergoing Hematopoietic Stem Cell Transplantation

Conditions
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Sinusoidal Obstruction Syndrome (SOS), Hematopoietic Stem Cell Transplant (HSCT)

Intervention / Treatment
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* Drug: N-acetylcysteine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men or women Age ≥ 18 years A proven diagnosis of one of the hematological malignancies: Acute Myeloid Leukemia, Acute Lymphoid Leukemia, Chronic Myeloid Leukemia, Chronic Lymphoid Leukemia, Multiple Myeloma, Non-Hodgkin's Lymphoma, Hodgkin's Lymphoma Patients must be scheduled to undergo of Allogeneic hematopoietic transplantation or HLA (Human Leukocyte Antigen) haploidentical related or Unrelated or HLA-matched related or autologous stem cell transplant Patients must be able to understand and sign a written informed consent Exclusion Criteria: Patient has a serious active disease or co-morbid medical condition, as judged by the investigator, which would interfere with the conduct of this study Patient, in the opinion of the investigator, may not be able to comply with the safety monitoring requirements of the study Known hypersensitivity to N-acetylcysteine Contraindications to perform any procedure provided for in this study Patients who have already undergone a previous transplant

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental: N-acetylcysteine<br>Sachets containing N-acetylcysteine 200 mg Powder for Oral Solution administered every 8 hours (Daily dose 600 mg/day). is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner | Drug: N-acetylcysteine<br>* Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo<br>|
| Placebo Comparator: Placebo Comparator: Placebo<br>200mg granulated solution of matching placebo administered every 8 hours (Daily dose 600 mg/day), is administered on the first day of conditioning and will continue until Day +30 post HSCT or hospital discharge, whichever is sooner | Drug: Placebo<br>* Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Presence or absence of SOS | To evaluate if prophylactic of N-acetylcysteine has an impact on the incidence of Sinusoidal obstruction syndrome (SOS) | Day + 30 post HSCT | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of SOS | Death as noted in medical record | within 30 days of bone marrow transplant | 
| Sinusoidal obstruction syndrome (SOS) -Free Survival at Day 30 Post-Hematopoietic Stem Cell Transplant (HSCT) | Comparison of efficacy of N-acetylcysteine vs Placebo for the prevention of SOS | 30 Days Post-Transplant | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stem cell transplant, Hematopoietic stem cell transplant (HSCT), Sinusoidal obstruction syndrome (SOS), Veno-occlusive disease (VOD), N-acetylcysteine