HIV/AIDS Tuberculous meningitis
Conditions
Interventions
Arm 1 Standard Antitubercular Therapy
Arm 2 Intensified Antitubercular Therapy and LZD
Arm 3 Intensified Antitubercular Therapy and LZD and ASA
Sponsors
Wellcome Trust University of Cape Town
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: HIV-1 seropositivity by rapid test, confirmed by enzyme-linked immunosorbent assay (regardless of ART status); Age 18 years or older; Tuberculous Meningitis defined as ‘possible’, ‘probable’ or ‘definite’ as per the published case definition[68]
Exclusion criteria
Exclusion criteria: Rifampicin-resistant M. tb detected in any microbiological specimen; History of allergy or hypersensitivity to H, E, R and Z, LZD or ASA; Received more than 5 days of antitubercular therapy in the 30 days prior to screening; Received a dose of ASA or any other NSAID within 2 weeks of screening; CSF unobtainable by lumbar puncture or another procedure; Evidence of bacterial or cryptococcal meningitis; Severe concurrent uncontrolled opportunistic infection including but not limited to active cytomegalovirus-associated disease, Kaposi sarcoma, Pneumocystis jirovecii pneumonia, HIV related or unrelated malignancy or gastrointestinal bleeding; Any other form of immunosuppressive therapy including antineoplastic and biologic agents apart from corticosteroids; Is pregnant in the third trimester; Peripheral neuropathy scoring Grade 3 or above on Brief Peripheral Neuropathy Score; Any disease or condition in which the use of the standard TB drugs or any of their components is contraindicated, including but not limited to allergy to any TB drug or their components; The presence of one or more of the following: - Estimated glomerular filtration rate (eGFR) 1.4 and/or clinical evidence of liver failure or decompensated cirrhosis - Hemoglobin < 8.0 g/dL - Platelets < 50 x109 /L - Neutrophils < 0.5 x 109 cells/L; The patient has any disease or condition in which any of the medicinal products listed in the section pertaining to prohibited medication (section xx) is used and cannot be safely stopped; The patient has a known or suspected, current or history of drug abuse, within the past 2 years, that is, in the opinion of the investigators, sufficient to compromise the safety or cooperation of the patient
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The incidence of solicited treatment-related AEs and death at 56 days associated with increased dose RIF plus LZD with or without adjunctive ASA, when administered alongside standard antitubercular | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Death (MRS 6) and disability (MRS 5) ;2. Death ;3. Disability, stratified by baseline MRC grade. ;4. Grade 3 or 4 AE. ;5. Permanent discontinuation of experimental drugs. ;6. Severity and frequency of haematologic and neurologic AE and hyperlactataemia related to LZD use. ;7. Severity and frequency of major bleeding (gastrointestinal and intracerebral) related to ASA use. ;8. M. tb culture status and time to positivity in automated liquid culture (MGIT) and Gene Xpert® Ultra cycle threshold (Ct) values ;9. The occurrence of TBM-IRIS assessed by the modified INSHI criteria [17]. ;10. MRI and CT changes | — |
Countries
South Africa
Contacts
Public ContactStephani;Angharad Grace Botha;Davis
Research Medical Officer ;Lead Investigator
Outcome results
None listed