View clinical trials related to Tuberculosis, Meningeal.
Filter by:Although tuberculosis is now considered a treatable disease, central nervous system tuberculosis (CNS-TB) when managed with the current standard-of-care (SOC), still has mortality rates ranging from 30-50% even in tertiary hospital centers. At present, the SOC for the management of CNS-TB is anti-tuberculous therapy with adjunctive corticosteroids. In CNS-TB, the activity of pathogenic host matrix metalloproteinases (MMPs) is unopposed to tissue inhibitors of metalloproteinases (TIMPs), resulting in a matrix-degrading phenotype which may drive worse outcomes in CNS-TB. In a prior established CNS-TB murine model, the investigators have demonstrated that adjunctive MMP inhibition using doxycycline, a widely available and cheap drug, in addition to standard TB treatment, compared with standard TB treatment alone, improved murine survival (Manuscript in preparation). The investigators previously showed that in humans with pulmonary TB, doxycycline with anti-TB treatment is safe, accelerates the resolution of inflammation, and suppresses systemic and respiratory MMPs. Hence, the investigators are now ideally positioned to determine if adjunctive doxycycline in patients with CNS-TB can improve clinical outcomes. The investigators will perform a Phase 2 double-blind randomized-controlled trial (RCT) of adjunctive doxycycline versus placebo with standard TB treatment and steroids for 8 weeks, with the primary outcome of 8-week mortality or severe neurological deficits.
Extrapulmonary TB (EPTB) accounts for nearly 30% of TB cases in HIV endemic settings, such as South Africa. The diagnosis of extrapulmonary TB is complicated by the poor performance of Gene Xpert and TB Culture in extrapulmonary fluid (30-50% sensitive), as well as the poor specificity of ADA. We can therefore not reliably use these tests to diagnose EPTB as effectively as we use them in sputum samples. The current best practice for diagnosing pleural TB is to perform a pleural biopsy, which is both invasive and costly. A rapid, easy to use test is needed to allow accurate and fast diagnosis of EPTB. Interferon-gamma is released at high concentrations in extrapulmonary fluid in active EPTB. Antrum Biotech has developed the IRISA-TB assay (validated and SAHPRA licenced) for the diagnosis of EPTB. The study will assess the real-world performance of IRISA-TB compared to ADA, Gene Xpert, and TB Culture when used to diagnose EPTB. We will evaluate IRISA-TB's performance in the following patient groups: - Suspected TB pleural effusion (n= 650) - Suspected TB pericardial effusion (n= 280) - Suspected TB peritonitis (n= 200) - Suspected TB meningitis (n = 1040) As part of our evaluation, we will ask clinicians who treat these patients to provide their feedback on IRISA-TB. We will ask them to indicate to what extent the IRISA-TB test helped them to make treatment decisions. Finally, we will conduct an economic assessment to determine the true cost of diagnosing and treating EPTB to the health system and patients, and we will determine how IRISA-TB could potentially result in cost savings.
Tuberculous meningitis (TBM) is the most lethal form of extra pulmonary tuberculosis. This devastating disease kills almost a third of its sufferers and disables a significant proportion of the survivors. TBM poses one of the most difficult diagnostic and therapeutic challenges in modern clinical practice. High-quality robust clinical trials have made a considerable contribution to the treatment of pulmonary tuberculosis in the last four decades. However, evidence from such clinical trials is lacking in TBM and the treatment remains uncertain. There is a significant variation in the choice, dose and duration of drugs between countries, institutions and clinicians. Investigators propose a multi-centric open-label clinical trial to assess the efficacy of short-course anti-TB drugs with high dose rifampicin, and moxifloxacin along with conventional anti-TB drugs and adjuvant therapy with aspirin and corticosteroids. Controls will receive standard treatment as per national guidelines for TBM. The investigators also aim to assess the safety and tolerability of high-dose Rifampicin and Moxifloxacin and the Pharmacodynamics and Pharmacokinetics parameters of ATT (Rifampicin, INH, Moxifloxacin and Pyrazinamide) in CSF between the two groups
Early diagnosis and appropriate treatment of tuberculous meningitis (TBM) are crucial steps to reduce morbidity and mortality. The WHO recommended to use Xpert MTB/RIF assay to diagnose pulmonary TB, pediatrics TB, extra pulmonary TB and rifampicin resistance. However, the data of accuracy in diagnosis of TBM is still lacking. This study aimed to find out the diagnostic performance of Xpert MTB/RIF assay for the diagnosis of tuberculous meningitis, especially in patients who presented with subacute lymphocytic meningitis.
The goal of this Diagnostic accuracy study is - To study sensitivity and specificity of sulcal tuberculomas in the diagnosis of tubercular meningitis and - To study the correlation of imaging findings in tubercular meningitis and spinal tubercular arachnoiditis with clinical outcomes after completion of therapy - Secondary objectives - To study the proportion of patients having clinical or imaging features of spinal tubercular arachnoiditis - To study the factors determining outcomes in patients with spinal tubercular arachnoiditis - To study the treatment trends in patients with spinal tubercular arachnoiditis The investigators will include [study Population] Patients with chronic meningitis as per criteria listed below - Chronic meningitis : Case definition - Headache with or without fever, nuchal stiffness and systemic symptoms AND - CSF suggestive of meningitis Pleocytosis (>20 cells per μL) with lymphocyte predominance (>50%) OR Protein concentration greater than age-specific normal value; especially >1•0 g/L OR Glucose concentration less than 60% of concentration in blood OR MRI suggestive of meningeal enhancement on contrast enhanced T1 sequences AND - Deemed by the treating physician that the syndrome is consistent with chronic meningitis - Patients who are positive for antibodies to HIV and pregnant females will also be included. - Willing to undergo periodic assessment clinically and with MRI as per clinical condition demands. The sensitivity and specificity of the finding of sulcal tuberculomas will be compared to the reference standard diagnostic criteria for the diagnosis of TB meningitis.
Randomized phase II clinical trial which aims to assess the impact on 3-month mortality and safety of adding adalimumab to standard treatment (anti-tuberculosis drugs and corticosteroids) in HIV patients with tuberculosis meningitis in 3 countries (Brazil, Mozambique, and Zambia).
The purpose of this study is to compare a 6-month regimen of high-dose rifampicin (RIF), high-dose isoniazid (INH), linezolid (LZD), and pyrazinamide (PZA) versus the World Health Organization (WHO) standard of care (SOC) treatment for tuberculosis meningitis (TBM).
Tubercular meningitis occurs in around 10% of those with extrapulmonary tuberculosis and is a major cause of mortality and morbidity. Inspite of effective Anti-tubercular drugs, still around 30% of patients develop complications due to arachnoiditis such as spinal tubercular radiculomyelitis, optico-chiasmatic arachnoiditis, development of new tuberculomas after starting therapy etc. which are probably immune mediated inflammatory responses due to paradoxical reaction to ATT. The management of arachnoiditis is far from satisfactory. High dose methylprednisolone, intrathecal hyaluronic acid, thalidomide have been tried in small case series and case reports. However, the results have not been satisfactory. There are two published reports of cyclophosphamide usage in TBM related vasculitis and stroke The investigators tried cyclophosphamide in four patients after consent, and found remarkable improvement in all of them. (Under peer review) In order to test this hypothesis, a randomized controlled trial is needed.
The rapid diagnosis of tuberculosis (TB) in children remains a serious challenge owing to limitations in the existing diagnostic tests. TB meningitis (TBM), an extrapulmonary form of TB, is the most severe manifestation of paediatric TB. TBM results in high morbidity and mortality in children, despite the availability of chemotherapy, mainly due to diagnostic delay. Most tests required for proper TBM diagnosis including analysis of cerebrospinal fluid (CSF) and brain imaging are not available in resource-limited settings e.g., in most of Africa including South Africa. New tests for TBM are urgently needed. The main goal of this proposal is to develop a point-of-care (POC) diagnostic test for TBM, based on CSF and bloodbiomarkers. Aim 1: Evaluate the diagnostic potentials of 51 host inflammatory biomarkers that the investigators recently identified in CSF and blood samples from children with suspected meningitis in a repository of 100 stored CSF and serum samples using a multiplex platform. After statistical analysis including multi-marker modelling by linear discriminant analysis, random forest, and other modelling techniques, the investigators will select the best combination of up to four biomarkers for incorporation into the prototype diagnostic test (Aim 2). Aim 2: Incorporate the best performing CSF and serum biomarkers into a novel, patented biosensor-based POC diagnostic test. The investigators will develop a multi-biomarker prototype test for detecting up to 4 biomarkers in serum or CSF. Aim 3: Evaluate the newly developed POC test on 300 children prospectively. This will be done at the Tygerberg Academic Hospital. The diagnostic yield of the POC test will be compared to the routine diagnostic tests.
INTENSE-TBM is randomized controlled, phase III, multicenter, 2 x 2 factorial plan superiority trial assessing the efficacity of two interventions to reduce mortality from tuberculous meningitis (TBM) in adolescents and adults with or without HIV-infection in sub-Saharan Africa: - Intensified TBM treatment with high-dose rifampicin and linezolid, compared to WHO standard TBM treatment. - Aspirin, compared to not receiving aspirin. The trial will be open-label for anti-TB treatment and placebo-controlled for aspirin treatment.