Intensified treatment for tuberculous meningitis to reduce mortality

Conditions

Tuberculous meningitis Infections and Infestations Tuberculosis of nervous system

A Dorothee Heemskerk, Mai Nguyen, Ha Thi Minh Dang, Nguyễn Văn Vĩnh Châu, Lan Huu Nguyen et al. (13 authors)

Clinical Infectious Diseases2017-03-1574 citations

10.1093/cid/cix230

Intensified Antituberculosis Therapy in Adults with Tuberculous Meningitis

A Dorothee Heemskerk, Nguyen Duc Bang, Nguyen T.H., Tran Thi Hong Chau, Nguyen Hoan Phu et al. (24 authors)

New England Journal of Medicine2016-01-14306 citations

10.1056/nejmoa1507062

Intensified treatment with high dose rifampicin and levofloxacin compared to standard treatment for adult patients with tuberculous meningitis (TBM-IT): protocol for a randomized controlled trial.

Heemskerk D, Day J, Chau TT, Dung NH, Yen NT, Bang ND, Merson L, Olliaro P, Pouplin T, Caws M, Wolbers M, Farrar J.

2011-02-0255 citations

10.1186/1745-6215-12-25

Sample size requirements for separating out the effects of combination treatments: randomised controlled trials of combination therapy vs. standard treatment compared to factorial designs for patients with tuberculous meningitis.

Wolbers M, Heemskerk D, Chau TT, Yen NT, Caws M, Farrar J, Day J.

2011-02-0214 citations

10.1186/1745-6215-12-26

Interventions

Patients will be randomised to one of two treatment groups: Group A: Rifampicin 15 mg/kg/day, levofloxacin 20 mg/kg/day, isonazid 5 mg/kg once daily (od) orally (po) (maximum of 300 mg

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: Greater or equal to 15 years of age (either sex) with a clinical diagnosis of tuberculous meningitis

Exclusion criteria

Exclusion criteria: 1. Positive cerebrospinal fluid (CSF) Gram or India Ink stain 2. Known or suspected pregnancy 3. Known hypersensitivity/intolerance to fluoroquinolones or rifampicin 4. Estimated glomerular filtration rate (GFR) less than 40 ml/min 5. Laboratory contraindications to antituberculous therapy: 5.1. Bilirubin greater than 2.5 x upper limit of normal (ULN) 5.2. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) greater than 5 x ULN 6. Lack of consent

Design outcomes

Secondary

Measure	Time frame
1. Neurological disability at 9 months as assessed using the 'simple questions' and Rankin score 2. Time to new neurological event. Neurological events are defined as: 2.1. Any of the following adverse events: cerebellar symptoms, coma, hemiplegia, neurological deteoriation, paraplegia, seizures, cerebral herniation or cranial nerve palsy 2.2. A fall in Glasgow Coma Score by greater than or equal to 2 points for greater than or equal to 2 days from highest previously recorded Glasgow Coma Score (including baseline) 3. Any grade 3 or 4 adverse event 4. Rate of treatment interruption for adverse events 5. The rates of asymptomatic transaminitis and symptomatic hepatitis 6. Time to new or recurrent acquired immune deficiency syndrome (AIDS) defining illness or death (in HIV-positive patients only) 7. Time to undetectable viral load, CD4 count at end of therapy (in HIV-positive patients only)	—

Measure

Time frame

1. Neurological disability at 9 months as assessed using the 'simple questions' and Rankin score 2. Time to new neurological event. Neurological events are defined as: 2.1. Any of the following adverse events: cerebellar symptoms, coma, hemiplegia, neurological deteoriation, paraplegia, seizures, cerebral herniation or cranial nerve palsy 2.2. A fall in Glasgow Coma Score by greater than or equal to 2 points for greater than or equal to 2 days from highest previously recorded Glasgow Coma Score (including baseline) 3. Any grade 3 or 4 adverse event 4. Rate of treatment interruption for adverse events 5. The rates of asymptomatic transaminitis and symptomatic hepatitis 6. Time to new or recurrent acquired immune deficiency syndrome (AIDS) defining illness or death (in HIV-positive patients only) 7. Time to undetectable viral load, CD4 count at end of therapy (in HIV-positive patients only)

—

Primary

Measure	Time frame
Overall survival during a follow-up period of 9 months	—

Countries

Viet Nam

Outcome results

None listed