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

NCT04712435 | Unknown Phase 2

• 1 other identifier: 33788420.4.0000.0072
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Sinusoidal Obstruction Syndrome (SOS); Hematopoietic Stem Cell Transplant (HSCT)

Keywords

Stem cell transplant; Hematopoietic stem cell transplant (HSCT); Sinusoidal obstruction syndrome (SOS); Veno-occlusive disease (VOD); N-acetylcysteine

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (2)

• Severity of SOS

  within 30 days of bone marrow transplant

• Sinusoidal obstruction syndrome (SOS) -Free Survival at Day 30 Post-Hematopoietic Stem Cell Transplant (HSCT)

  30 Days Post-Transplant

Study Arms (2)

Experimental: N-acetylcysteine

EXPERIMENTAL

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

Placebo Comparator: Placebo

PLACEBO COMPARATOR

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

Interventions

N-acetylcysteine DRUG

Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo

Experimental: N-acetylcysteine

Placebo DRUG

Eligible patients will be randomised to receive N-acetylcysteine versus matching placebo

Placebo Comparator: Placebo

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Instituto Brasileiro de Controle do Cancer: lead

Study Sites (1)

Jamilla Neves Cavalcante

São Paulo, São Paulo, 03102-002, Brazil

Location

Related Publications (6)

• Dignan FL, Wynn RF, Hadzic N, Karani J, Quaglia A, Pagliuca A, Veys P, Potter MN; Haemato-oncology Task Force of British Committee for Standards in Haematology; British Society for Blood and Marrow Transplantation. BCSH/BSBMT guideline: diagnosis and management of veno-occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation. Br J Haematol. 2013 Nov;163(4):444-57. doi: 10.1111/bjh.12558. Epub 2013 Sep 17.

  PMID: 24102514 BACKGROUND

• Mohty M, Malard F, Abecassis M, Aerts E, Alaskar AS, Aljurf M, Arat M, Bader P, Baron F, Bazarbachi A, Blaise D, Ciceri F, Corbacioglu S, Dalle JH, Duarte RF, Fukuda T, Huynh A, Masszi T, Michallet M, Nagler A, NiChonghaile M, Pagluica T, Peters C, Petersen FB, Richardson PG, Ruutu T, Savani BN, Wallhult E, Yakoub-Agha I, Carreras E. Sinusoidal obstruction syndrome/veno-occlusive disease: current situation and perspectives-a position statement from the European Society for Blood and Marrow Transplantation (EBMT). Bone Marrow Transplant. 2015 Jun;50(6):781-9. doi: 10.1038/bmt.2015.52. Epub 2015 Mar 23.

  PMID: 25798682 BACKGROUND

• Dalle JH, Giralt SA. Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment. Biol Blood Marrow Transplant. 2016 Mar;22(3):400-9. doi: 10.1016/j.bbmt.2015.09.024. Epub 2015 Oct 23.

  PMID: 26431626 BACKGROUND

• Ozdemir ZC, Turhan AB, Eren M, Bor O. Is N-acetylcysteine infusion an effective treatment option in L-asparaginase associated hepatotoxicity? Blood Res. 2017 Mar;52(1):69-71. doi: 10.5045/br.2017.52.1.69. Epub 2017 Mar 27. No abstract available.

  PMID: 28401107 BACKGROUND

• Barkholt L, Remberger M, Hassan Z, Fransson K, Omazic B, Svahn BM, Karlsson H, Brune M, Hassan M, Mattsson J, Ringden O. A prospective randomized study using N-acetyl-L-cysteine for early liver toxicity after allogeneic hematopoietic stem cell transplantation. Bone Marrow Transplant. 2008 May;41(9):785-90. doi: 10.1038/sj.bmt.1705969. Epub 2008 Jan 7.

  PMID: 18176610 BACKGROUND

• Ringden O, Remberger M, Lehmann S, Hentschke P, Mattsson J, Klaesson S, Aschan J. N-acetylcysteine for hepatic veno-occlusive disease after allogeneic stem cell transplantation. Bone Marrow Transplant. 2000 May;25(9):993-6. doi: 10.1038/sj.bmt.1702387.

  PMID: 10800069 BACKGROUND

MeSH Terms

Conditions

Hepatic Veno-Occlusive Disease

Interventions

Acetylcysteine

Condition Hierarchy (Ancestors)

Liver Diseases; Digestive System Diseases; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

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

Study Officials

• Jamilla N Cavalcante, MD

  IBCC Oncologia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jamilla N Cavalcante, MD

CONTACT

+55113474-4428; millacavalcante@hotmail.com

Alayne D Yamada, PhD

CONTACT

+55113474-4242; alayne.pesquisa@ibcc-mooca.org.br

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Matching placebo
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: This is a single-center, randomized, placebo-controlled study to evaluate the efficacy and safety of N-acetylcysteine

Study Record Dates

• First Submitted: January 13, 2021
• First Posted: January 15, 2021
• Study Start: April 1, 2021
• Primary Completion: March 31, 2023
• Study Completion: March 31, 2023
• Last Updated: March 9, 2021

Record last verified: 2021-01

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)