Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial

Wellcome Open Research

article

Joseph Donovan¹  Nguyen Hoan Phu³  Nguyen Thi Hoang Mai³  Le Tien Dung⁴  Darma Imran⁵  Erlina Burhan⁶  Lam Hong Bao Ngoc¹  Nguyen Duc Bang⁴  Do Chau Giang⁴  Dang Thi Minh Ha⁴  Jeremy Day¹  Le Thi Phuong Thao¹  Nguyen TT Thuong¹  Nguyen Nang Vien⁴  Ronald B. Geskus¹  Marcel Wolbers¹  Raph L Hamers²  Reinout van Crevel²  Mugi Nursaya²  Kartika Maharani⁵  Tran Tinh Hien¹  Kevin Baird²  Nguyen Huu Lan⁴  Evelyne Kestelyn¹  Nguyen Van Vinh Chau³  Guy E. Thwaites¹ 

[1] Oxford University Clinical Research Unit;Centre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford;Hospital for Tropical Diseases;Pham Ngoc Thach Hospital;Cipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia;Persahabatan Hospital, Faculty of Medicine, Universitas Indonesia;Eijkman Oxford Clinical Research Unit, Eijkman Institute of Molecular Biology;Department of Medicine and Radboud Center for Infectious Diseases ,(RCI), Radboud University Medical Center

关键词: Tuberculous meningitis;    HIV;    Dexamethasone;    Drug-induced liver injury;    LTA4H;    Adrenal suppression;    Diabetes;    Strongyloides;    Hyponatraemia;   

DOI  :  10.12688/wellcomeopenres.14006.2

学科分类：内科医学

来源: Wellcome

【 摘 要 】

Background: Tuberculous meningitis (TBM) is the most severe form of tuberculosis. Co-infection with HIV increases the risk of developing TBM, complicates treatment, and substantially worsens outcome. Whether corticosteroids confer a survival benefit in HIV-infected patients with TBM remains uncertain. Hepatitis is the most common drug-induced serious adverse event associated with anti-tuberculosis treatment, occurring in 20% of HIV-infected patients. The suggested concentration thresholds for stopping anti-tuberculosis drugs are not evidence-based. This study aims to determine whether dexamethasone is a safe and effective addition to the first 6-8 weeks of anti-tuberculosis treatment of TBM in patients with HIV, and investigate alternative management strategies in a subset of patients who develop drug induced liver injury (DILI) that will enable the safe continuation of rifampicin and isoniazid therapy. Methods: We will perform a parallel group, randomised (1:1), double blind, placebo-controlled multi-centre Phase III trial, comparing the effect of dexamethasone versus placebo on overall survival in HIV-infected patients with TBM, in addition to standard anti-tuberculosis and antiretroviral treatment. The trial will be set in two hospitals in Ho Chi Minh City, Vietnam, and two hospitals in Jakarta, Indonesia. The trial will enrol 520 HIV-infected adults. An ancillary study will perform a randomised comparison of three DILI management strategies with the aim of demonstrating which strategy results in the least interruption in rifampicin and isoniazid treatment. An identical ancillary study will also be performed in the linked randomised controlled trial of dexamethasone in HIV-uninfected adults with TBM stratified by LTA4H genotype (LAST ACT). Discussion: Whether corticosteroids confer a survival benefit in HIV-infected patients remains uncertain, and the current evidence base for using corticosteroids in this context is limited. Interruptions in anti-tuberculosis chemotherapy is a risk factor for death from TBM. Alternative management strategies in DILI may allow the safe continuation of rifampicin and isoniazid therapy.

【 授权许可】

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