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

A vizsgálat adatai

Ki végzi

ANRS, Emerging Infectious Diseases

Azonosító

NCT04145258

A regiszteradat frissítve

2026. június 24.

Eredeti leírás

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:A teljes eredeti leírásKevesebb

Intensified Tuberculosis Treatment to Reduce the Mortality of HIV-infected and Uninfected Patients With Tuberculosis Meningitis: a Phase III Randomized Controlled Trial (Acronym: INTENSE-TBM)

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.

Bevonási feltételek: Age ≥ 15 years; TBM defined as "definite", "probable" or "possible"; 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.

Kizáró feltételek: Major surgery within the last two weeks prior to inclusion; Current use of drugs contraindicated with study drugs and that cannot be safely stopped (see Appendix 1: Drugs contra-indicated with study drugs); Clinical evidence of liver failure or decompensated cirrhosis; Documented M. tuberculosis resistance to rifampicin; 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; 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; 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; > 5 days of TB treatment; 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); Positive gram-stain, bacterial culture or cryptococcal antigen in the Cerebral Spinal Fluid; Ongoing chronic aspirin treatment (eg for cardiovascular risk); Any reason which at the discretion of the investigator would compromise safety and cooperation in the trial.

ClinicalTrials.gov NCT04145258