Intensified Tuberculosis Treatment to Reduce the Mortality of Patients With Tuberculous Meningitis

Launched by ANRS, EMERGING INFECTIOUS DISEASES · Oct 28, 2019

Keywords

ClinConnect Summary

The INTENSE-TBM trial is studying new treatment options to help reduce the risk of death in patients with tuberculous meningitis (TBM), a serious type of meningitis caused by tuberculosis. This trial is looking at two specific approaches: one involves using higher doses of two medications, rifampicin and linezolid, compared to standard treatment recommended by the World Health Organization. The second approach is testing whether taking aspirin can help patients improve compared to those who do not take it. This study is open to adults and adolescents aged 15 and older, including those with HIV, who have been diagnosed with definite, probable, or possible TBM.

Participants in this trial can expect to be randomly assigned to receive either the new treatment or the standard care. It’s important to note that there are specific criteria for joining the trial, such as not having started TB treatment for more than five days and not having certain medical conditions like serious kidney problems or active bleeding. The trial is currently recruiting participants, and those who take part will receive close monitoring and care throughout the study. This research aims to find better ways to treat TBM and improve survival rates for patients affected by this illness.

Gender

ALL

Eligibility criteria

• Inclusion criteria:
• • 1. Age ≥ 15 years
• • 2. TBM defined as "definite", "probable" or "possible"
• • 3. Signed Informed Consent
• • Definite TBM = at least one of the following criteria: acid-fast bacilli seen in CSF microscopy, positive CSF M. tuberculosis culture, or positive CSF M. tuberculosis commercial nucleic acid amplification test.
• • Probable TBM = total modified Marais score ≥12 when neuroimaging is available, or ≥10 when neuroimaging is not available (at least 2 points should come from CSF or cerebral imaging criteria).
• • Possible TBM = total modified Marais 6-11 when neuroimaging is available, or 6-9 when neuroimaging is not available.
• Exclusion criteria:
• • \> 5 days of TB treatment
• • Renal failure (eGFR\<30 ml/min, CKD-EPI formula).
• • Neutrophil count \< 0.6 x 109/L.
• • Hemoglobin concentration \< 8 g/dL.
• • Total bilirubin \> 2.6 times the Upper Limit of Normal
• • Platelet count \< 50 x 109/L.
• • ALT \> 5 times the Upper Limit of Normal.
• • Clinical evidence of liver failure or decompensated cirrhosis.
• • For women: more than 17 weeks pregnancy or breastfeeding.
• • For patients without decrease level of consciousness (Glasgow Coma Scale = 15): Peripheral neuropathy scoring Grade 3 or above on the Brief Peripheral Neuropathy Score (BPNS).
• • Documented M. tuberculosis resistance to rifampicin.
• • Positive gram-stain, bacterial culture or cryptococcal antigen in the Cerebral Spinal Fluid.
• • Evidence of active bleeding (hemoptysis, gastrointestinal bleeding, hematuria, intracranial bleeding).
• • Inability to collect Cerebral Spinal Fluid, except for patients with confirmed tuberculosis (by rapid molecular test or culture) from another biological sample and clinical and/or CT scan evidence of meningitis.
• • Major surgery within the last two weeks prior to inclusion.
• • Ongoing chronic aspirin treatment (eg for cardiovascular risk).
• • Current use of drugs contraindicated with study drugs and that cannot be safely stopped (see Appendix 1: Drugs contra-indicated with study drugs).
• * In available history from patients:
• • Evidence of past intracranial bleeding.
• • Evidence of past of peptic ulceration.
• • Evidence of recent (\< 3 month) gastrointestinal bleeding.
• • Known hypersensitivity contraindicating the use of study drugs .
• • Evidence of porphyria.
• • Evidence of hyperuricemia or gout.
• • Any reason which at the discretion of the investigator would compromise safety and cooperation in the trial.