Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations]
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 uncertai...
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| Format: | Article |
| Language: | English |
| Published: |
Wellcome
2018-06-01
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| Series: | Wellcome Open Research |
| Online Access: | https://wellcomeopenresearch.org/articles/3-31/v2 |
| _version_ | 1818528194275311616 |
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| author | Joseph Donovan Nguyen Hoan Phu Nguyen Thi Hoang Mai Le Tien Dung Darma Imran Erlina Burhan Lam Hong Bao Ngoc Nguyen Duc Bang Do Chau Giang Dang Thi Minh Ha Jeremy Day Le Thi Phuong Thao Nguyen TT Thuong Nguyen Nang Vien Ronald B. Geskus Marcel Wolbers Raph L Hamers Reinout van Crevel Mugi Nursaya Kartika Maharani Tran Tinh Hien Kevin Baird Nguyen Huu Lan Evelyne Kestelyn Nguyen Van Vinh Chau Guy E. Thwaites |
| author_facet | Joseph Donovan Nguyen Hoan Phu Nguyen Thi Hoang Mai Le Tien Dung Darma Imran Erlina Burhan Lam Hong Bao Ngoc Nguyen Duc Bang Do Chau Giang Dang Thi Minh Ha Jeremy Day Le Thi Phuong Thao Nguyen TT Thuong Nguyen Nang Vien Ronald B. Geskus Marcel Wolbers Raph L Hamers Reinout van Crevel Mugi Nursaya Kartika Maharani Tran Tinh Hien Kevin Baird Nguyen Huu Lan Evelyne Kestelyn Nguyen Van Vinh Chau Guy E. Thwaites |
| author_sort | Joseph Donovan |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T06:46:30Z |
| format | Article |
| id | doaj.art-ac29a6757e1442f5a7efee484ed1bec4 |
| institution | Directory Open Access Journal |
| issn | 2398-502X |
| language | English |
| last_indexed | 2024-12-11T06:46:30Z |
| publishDate | 2018-06-01 |
| publisher | Wellcome |
| record_format | Article |
| series | Wellcome Open Research |
| spelling | doaj.art-ac29a6757e1442f5a7efee484ed1bec42022-12-22T01:17:04ZengWellcomeWellcome Open Research2398-502X2018-06-01310.12688/wellcomeopenres.14006.215979Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations]Joseph Donovan0Nguyen Hoan Phu1Nguyen Thi Hoang Mai2Le Tien Dung3Darma Imran4Erlina Burhan5Lam Hong Bao Ngoc6Nguyen Duc Bang7Do Chau Giang8Dang Thi Minh Ha9Jeremy Day10Le Thi Phuong Thao11Nguyen TT Thuong12Nguyen Nang Vien13Ronald B. Geskus14Marcel Wolbers15Raph L Hamers16Reinout van Crevel17Mugi Nursaya18Kartika Maharani19Tran Tinh Hien20Kevin Baird21Nguyen Huu Lan22Evelyne Kestelyn23Nguyen Van Vinh Chau24Guy E. Thwaites25Oxford University Clinical Research Unit, Ho Chi Minh City, VietnamHospital for Tropical Diseases, Ho Chi Minh City, VietnamHospital for Tropical Diseases, Ho Chi Minh City, VietnamPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamCipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaPersahabatan Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaOxford University Clinical Research Unit, Ho Chi Minh City, VietnamPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKCipto Mangunkusumo Hospital, Faculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaOxford University Clinical Research Unit, Ho Chi Minh City, VietnamCentre for Tropical Medicine and Global Health, Nuffield Department of Medicine, University of Oxford, Oxford, UKPham Ngoc Thach Hospital, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamHospital for Tropical Diseases, Ho Chi Minh City, VietnamOxford University Clinical Research Unit, Ho Chi Minh City, VietnamBackground: 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.https://wellcomeopenresearch.org/articles/3-31/v2 |
| spellingShingle | Joseph Donovan Nguyen Hoan Phu Nguyen Thi Hoang Mai Le Tien Dung Darma Imran Erlina Burhan Lam Hong Bao Ngoc Nguyen Duc Bang Do Chau Giang Dang Thi Minh Ha Jeremy Day Le Thi Phuong Thao Nguyen TT Thuong Nguyen Nang Vien Ronald B. Geskus Marcel Wolbers Raph L Hamers Reinout van Crevel Mugi Nursaya Kartika Maharani Tran Tinh Hien Kevin Baird Nguyen Huu Lan Evelyne Kestelyn Nguyen Van Vinh Chau Guy E. Thwaites Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] Wellcome Open Research |
| title | Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] |
| title_full | Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] |
| title_fullStr | Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] |
| title_full_unstemmed | Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] |
| title_short | Adjunctive dexamethasone for the treatment of HIV-infected adults with tuberculous meningitis (ACT HIV): Study protocol for a randomised controlled trial [version 2; referees: 1 approved, 2 approved with reservations] |
| title_sort | adjunctive dexamethasone for the treatment of hiv infected adults with tuberculous meningitis act hiv study protocol for a randomised controlled trial version 2 referees 1 approved 2 approved with reservations |
| url | https://wellcomeopenresearch.org/articles/3-31/v2 |
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