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

NCT ID: NCT04712435

Last Updated: 2021-03-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2
• Total Enrollment: 80 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2023-03-31

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.

Conditions

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: DOUBLE

Study Groups

Experimental: 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

Group Type: EXPERIMENTAL

N-acetylcysteine

Intervention Type: DRUG

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

Placebo Comparator: 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

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

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

Interventions

N-acetylcysteine

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

Intervention Type: DRUG

Placebo

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

Intervention Type: DRUG

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Instituto Brasileiro de Controle do Cancer

OTHER

Sponsor Role: lead

Responsible Party

Jamilla Neves Cavalcante

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jamilla N Cavalcante, MD

Role: PRINCIPAL_INVESTIGATOR

IBCC Oncologia

Locations

Jamilla Neves Cavalcante

São Paulo, São Paulo, Brazil

Countries

Brazil

Central Contacts

Jamilla N Cavalcante, MD

Role: CONTACT

millacavalcante@hotmail.com

+55113474-4428

Alayne D Yamada, PhD

Role: CONTACT

alayne.pesquisa@ibcc-mooca.org.br

+55113474-4242

Facility Contacts

Jamilla N Cavalcante, MD

Role: primary

millacavalcante@hotmail.com

+55113474-4428

Alayne D Yamada, PhD

Role: backup

alayne.pesquisa@ibcc-mooca.org.br

+55113474-4242

References

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.

Reference Type: BACKGROUND

PMID: 24102514 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 25798682 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 26431626 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 28401107 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18176610 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 10800069 (View on PubMed)

Other Identifiers

33788420.4.0000.0072

Identifier Type: -

Identifier Source: org_study_id