Woman and Man
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Extract
Background and study aims Infection with bacteria called M. tuberculosis causes tuberculosis and is generally treated with a course of four or five types of antibiotic drugs. In cases of tuberculous meningitis (TBM), the bacteria has gotten into a patient's brain and spinal cord, causing life-threatening inflammation. It is estimated that almost one third of patients with TBM die, despite treatment. HIV patients have a worse prognosis - about two thirds of patients with both TBM and HIV die. Without treatment all patients with TBM die. The investigators of this study believe that the usual course of antibiotic drugs often does not work as well for TBM as for tuberculosis of the lungs, because the drugs are not able to effectively penetrate to the patient's brain to treat the infection there. This study examines the effect of increased dosages and addition of drugs to the standard course of antibiotics for patients with TBM, in order to optimise the killing of bacteria in the brain. Who can participate? The study aims to recruit 750 patients with TBM to the study, including patients with HIV. Patients need to be over 18 years of age, have a clinical diagnosis of TBM, and give informed consent to participate. What does the study involve? Patients are randomly allocated to one of two treatment groups. The intensified treatment group receives the normal course of anti-tuberculosis treatment, plus levofloxacin and increased dosages of rifampicin. The standard treatment group receives the normal course of anti-tuberculosis treatment, plus placebo (dummy) pills that look the same as levofloxacin and rifampicin, but do not contain the actual drug. By giving one group placebo pills, neither the patient nor the doctor can know which group a patient belongs to. This is the best way to study the difference in outcome in the end. The patients are monitored daily for general health, drug side-effects and mental status. Blood and brain fluid (cerebrospinal fluid) testing is carried out on multiple occasions. Patients are monitored daily by a study doctor while in the hospital until they are discharged, generally after one month of treatment. When in hospital, blood will be drawn each week, or if the treating doctor thinks it is necessary it will be checked more often. They are then followed up each month at the outpatient department until the end of treatment at 9 total months or until the patient dies or withdraws from the study. Lumbar punctures (taking fluid from the spine by a hollow needle in the lower back) will be carried out when admitted to hospital and after 1, 2 and 9 months, in order to see if the infection is clearing. If the treating doctor thinks it is necessary they may be done more often. As per hospital procedure, patients may object to the procedure - this will not influence their treatment. What are the possible benefits and risks of participating? These drugs are generally known to be safe. There is a lot of information about side affects of these drugs in patients with tuberculosis or with other infections and in general the side effects are mild. The most common side effects are abdominal (stomach) problems, such as vomiting or diarrhoea and inflammation of the liver for rifampicin. Levofloxacin is also well tolerated, but can cause abdominal problems, headache and dizziness and in very rare cases inflammation of tendons and cardiac problems. Some patients with cardiac problems in the past may be at greater risk for developing cardiac side effects, so all patients in the study will get an ECG done on separate occasions to check whether it is safe to give this drug and whether problems develop during treatment. The treatment and tests during the study period will be paid for by the study team. For poor patients this may be a benefit of being in the study. Where is the study run from? This study is run by researchers at the Oxford University Clinical Research Unit in Vietnam, in partnership with the Hospital for Tropical Diseases and Pham Ngoc Thach Hospital in Ho Chi Minh City, the two study sites. When is the study starting and how long is it expected to run for? The study began in April 2011 and is expected to finish in March 2015. Who is funding the study? The Wellcome Trust (UK). Who is the main contact? Clinical Trials Unit at the Oxford University Clinical Research Unit in Vietnam Tel: +84 839 241 983
Inclusion criteria
- Tuberculous meningitis