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

Phase 2

• Conditions: Sinusoidal Obstruction Syndrome (SOS); Hematopoietic Stem Cell Transplant (HSCT)
• Interventions: Drug: Placebo; Drug: N-acetylcysteine

• Registration Number: NCT04712435
• Lead Sponsor: Instituto Brasileiro de Controle do Cancer

Brief Summary

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

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.

Study Timeline

• Status Verified: 2021-01
• Study First Submitted: 2021-01-13
• Study First Submitted QC: 2021-01-13
• Study First Posted: 2021-01-15
• Last Update Submitted: 2021-03-08
• Last Update Posted: 2021-03-09
• Study Start: 2021-04
• Primary Completion: 2023-03-31
• Study Completion: 2023-03-31

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo Comparator: Placebo	Placebo	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
Experimental: N-acetylcysteine	N-acetylcysteine	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

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Jamilla Neves Cavalcante; 🇧🇷 Sao Paulo, SP, Brazil