[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"health-study-detail:100484623":3},{"organization":4,"outcomesModule":7,"designInfo":61,"detailedDescription":68,"studyPopulation":11,"armGroups":69,"interventions":80,"overallOfficials":86,"centralContacts":94,"locations":102,"responsibleParty":159,"collaborators":11,"id":161,"slug":162,"hasResults":163,"nctId":164,"briefTitle":165,"officialTitle":166,"acronym":167,"eligibilityCriteria":168,"healthyVolunteers":163,"sex":169,"minAge":170,"maxAge":11,"enrollmentInfo":171,"targetDuration":11,"studyType":174,"phases":175,"briefSummary":177,"conditions":178,"keywords":11,"overallStatus":105,"whyStopped":11,"lastUpdateSubmitDate":181,"lastUpdatePostDateStruct":182,"startDateStruct":185,"completionDateStruct":187,"leadSponsor":189,"locationsCount":190},{"fullName":5,"class":6},"ANRS, Emerging Infectious Diseases","OTHER_GOV",{"primaryOutcomes":8,"secondaryOutcomes":13,"otherOutcomes":11},[9],{"measure":10,"description":11,"timeFrame":12},"3-month all-cause mortality",null,"3 months",[14,16,18,20,23,27,30,32,35,37,40,43,45,47,49,52,54,58],{"measure":15,"description":11,"timeFrame":12},"3-month incidence of severe\u002Flife threatening bacterial infections and opportunistic infections",{"measure":17,"description":11,"timeFrame":12},"3-month incidence of grade 3 and 4 adverse reactions and those leading to ART or anti tuberculosis treatment (ATT) interruption",{"measure":19,"description":11,"timeFrame":12},"3-month incidence of all grade 3 and 4 adverse events",{"measure":21,"description":11,"timeFrame":22},"9-month and 12-month all-cause mortality","9 months and 12 months",{"measure":24,"description":25,"timeFrame":26},"9-month disability free survival (using Rankin score)","MODIFIED RANKIN SCORE (MRS) 0: No symptoms at all\n\n1. No significant disability despite symptoms; able to carry out all usual duties and activities\n2. Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance\n3. Moderate disability; requiring some help, but able to walk without assistance\n4. Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance\n5. Severe disability; bedridden, incontinent and requiring constant nursing care and attention\n6. Dead","9 months",{"measure":28,"description":11,"timeFrame":29},"3-month and 9-month incidence of all grade infectious diseases and opportunistic infections","3 months and 9 months",{"measure":31,"description":25,"timeFrame":26},"9-month neurological disability score (Rankin score)",{"measure":33,"description":11,"timeFrame":34},"Time to and severity of TB-associated paradoxical immune reconstitution inflammatory syndrome (IRIS) between D0 and 9 months","up to 9 months",{"measure":36,"description":11,"timeFrame":34},"Time to discharge",{"measure":38,"description":11,"timeFrame":39},"Cerebrospinal fluid (CSF) pleocytosis\u002Fprotein\u002Fglucose levels at W0, W1 and W4","week 0, week1 and week4",{"measure":41,"description":11,"timeFrame":42},"CSF mycobacterial cultures negativation (culture conversion), time to culture positivity and cycle threshold (GeneXpert Mycobacterium tuberculosis\u002FRifampicin Ultra) at W1, W4,","week1 and week4",{"measure":44,"description":11,"timeFrame":26},"Proportion of patients with HIV-1 RNA\u003C50 copies\u002FmL at 9 months",{"measure":46,"description":11,"timeFrame":26},"CD4 counts at 9 months (and gain from baseline)",{"measure":48,"description":11,"timeFrame":39},"Inflammatory biomarkers and cytokines profiles in CSF at W0, W1, W4",{"measure":50,"description":11,"timeFrame":51},"Inflammatory biomarkers in blood at W0, W4, W10, M6 and M9","week 0, week4, week10, 6 months and 9 months",{"measure":53,"description":11,"timeFrame":51},"Cytokines profiles in blood at W0, W4, W10, M6 and M9",{"measure":55,"description":56,"timeFrame":57},"Proportion of participants with possible, probable or definite TBM diagnosis at pre-inclusion according to Marais score","Evaluation of TBM diagnosis and differential diagnoses in all pre-included participants: Proportion of participants with possible, probable or definite TBM diagnosis at pre-inclusion according to Marais score","Pre-inclusion",{"measure":59,"description":60,"timeFrame":57},"Proportion of participants with other CNS disease (opportunistic infections or other neurological conditions)","Evaluation of TBM diagnosis and differential diagnoses in all pre-included participants: Proportion of participants with other CNS disease (opportunistic infections or other neurological conditions)",{"allocation":62,"interventionModel":63,"interventionModelDescription":64,"primaryPurpose":65,"observationalModel":11,"timePerspective":11,"maskingInfo":66},"RANDOMIZED","PARALLEL","Phase II multicenter, open-label, randomized, proof of concept, comparative trial with a large alpha (type 1 error rate).\n\nAll HIV1-infected patients diagnosed with TBM will be started on standard TB therapy for the duration recommended by national guidelines (2 months intensive phase and 7 months maintenance phase) and high-dose dexamethasone up to 4 weeks.\n\nAs soon as possible during the first 3 days of the standard TBM treatment that includes antituberculosis treatment and high-dose steroids, consenting patients will be randomized to standard treatment alone or standard treatment + adalimumab. Randomization will be stratified on country and initial severity using the British Medical Research Council (MRC) score.\n\nAdalimumab arm:\n\n* Standard TBM treatment as described above\n* Adalimumab 40 mg: one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids","TREATMENT",{"masking":67,"maskingDescription":11,"whoMasked":11},"NONE","Phase II multicenter, open-label, randomized, proof of concept, comparative trial with a large alpha (type 1 error rate) to evaluate the impact on 3-month mortality of adding the tumor necrosis factor inhibitor adalimumab to the standard treatment with antituberculosis drugs and high-dose steroids in HIV-infected adults diagnosed with tuberculosis meningitis (TBM) in 3 countries (Brazil, Mozambique, and Zambia).\n\nAll HIV1-infected patients diagnosed with TBM will be started on standard TB therapy for the duration recommended by national guidelines (2 months intensive phase and 7 months maintenance phase) and high-dose dexamethasone up to 4 weeks.\n\nAs soon as possible during the first 3 days of the standard TBM treatment that includes antituberculosis treatment and high-dose steroids, consenting patients will be randomized to standard treatment alone or standard treatment + adalimumab. Randomization will be stratified on country and initial severity using the British Medical Research Council (MRC) score.\n\nAdalimumab arm:\n\n* Standard TBM treatment as described above\n* Adalimumab 40 mg: one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids As World Health Organization and national guidelines for early antiretroviral therapy (ART) introduction in patients with TBM advise caution, ART will be started after 4 weeks of TB treatment in both arms if patients are clinically improved (but no later than 8 weeks of anti-TB treatment).\n\nAn interim analysis will be performed after 20 patients have been followed up for 3 months in adalimumab arm. This interim analysis will monitor the safety of adding TNF-inhibitor adalimumab.",[70,76],{"label":71,"type":72,"description":73,"interventionNames":74},"Adalimumab arm","EXPERIMENTAL","* Standard TBM treatment\n* Adalimumab 40 mg: one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids",[75],"Drug: Adalimumab Injection",{"label":77,"type":78,"description":79,"interventionNames":11},"Control arm","NO_INTERVENTION","\\- Standard TBM",[81],{"type":82,"name":83,"description":84,"armGroupLabels":85,"otherNames":11},"DRUG","Adalimumab Injection","one sub-cutaneous injection, every 2 weeks for 10 weeks (total 6 injections), started as soon as possible during the first 3 days of antituberculosis treatment and high-dose steroids",[71],[87,91],{"name":88,"affiliation":89,"role":90},"Nathalie DE CASTRO, MD","AP-HP, Hôpital Saint-Louis","PRINCIPAL_INVESTIGATOR",{"name":92,"affiliation":93,"role":90},"Celso KHOSA, MD","Instituto Nacional de Saúde, Mozambique",[95,100],{"name":96,"role":97,"phone":98,"phoneExt":11,"email":99},"Vanessa MACHAULT, PhD","CONTACT","+335 57 57 57 63","vanessa.machault@u-bordeaux.fr",{"name":101,"role":97,"phone":11,"phoneExt":11,"email":11},"Olivier MARCY, MD PhD",[103,123,140],{"facility":104,"status":105,"city":106,"state":11,"zip":107,"country":108,"countryCode":109,"cosmosGeoPoint":110,"geoPoint":115,"contacts":116},"Laboratory of clinical research on STD\u002FAIDS - IPEC\u002FFIOCRUZ","RECRUITING","Rio de Janeiro","21040-900","Brazil","BR",{"type":111,"coordinates":112},"Point",[113,114],-43.18223,-22.90642,{"lat":114,"lon":113},[117,121],{"name":118,"role":97,"phone":119,"phoneExt":11,"email":120},"Sandra WAGNER","+ 55 21 38 65 96 23","dra.wagner@gmail.com",{"name":122,"role":90,"phone":11,"phoneExt":11,"email":11},"Beatriz GRINSZTEJN",{"facility":124,"status":125,"city":126,"state":11,"zip":11,"country":127,"countryCode":128,"cosmosGeoPoint":129,"geoPoint":133,"contacts":134},"Instituto Nacional de Saude","NOT_YET_RECRUITING","Maputo","Mozambique","MZ",{"type":111,"coordinates":130},[131,132],32.58322,-25.96553,{"lat":132,"lon":131},[135,138],{"name":136,"role":97,"phone":11,"phoneExt":11,"email":137},"Marcia CHILUVANE","marcia.chiluvane@ins.gov.mz",{"name":139,"role":90,"phone":11,"phoneExt":11,"email":11},"Celso KHOSA",{"facility":141,"status":125,"city":142,"state":11,"zip":11,"country":143,"countryCode":144,"cosmosGeoPoint":145,"geoPoint":149,"contacts":150},"Adult Infectious Diseases Centre, University Teaching Hospital","Lusaka","Zambia","ZM",{"type":111,"coordinates":146},[147,148],28.28713,-15.40669,{"lat":148,"lon":147},[151,154,157],{"name":152,"role":97,"phone":11,"phoneExt":11,"email":153},"Christabel Phiri","chigweyassin@gmail.com",{"name":155,"role":97,"phone":11,"phoneExt":11,"email":156},"Seke Muzazu","sekemuzazu@gmail.com",{"name":158,"role":90,"phone":11,"phoneExt":11,"email":11},"Ducan CHANDA",{"type":160,"investigatorFullName":11,"investigatorTitle":11,"investigatorAffiliation":11,"oldNameTitle":11,"oldOrganization":11},"SPONSOR","100484623","phase-2-tnf-inhibitors-to-reduce-mortality-in-hiv-1-infected-patients-with-tuberculosis-meningitis-100484623",false,"NCT05590455","Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis","ANRS 12404 TIMPANI: Tnf Inhibitors to Reduce Mortality in HIV-1 Infected PAtients With Tuberculosis meNIngitis: a Phase II, Multicenter, Randomized Clinical Trial","TIMPANI","Inclusion Criteria:\n\n* Age ≥18 years\n* HIV-1 infection\n* Definite or probable tuberculosis meningitis\n* Standard tuberculosis meningitis treatment ≤3 days: anti TB drugs at standard doses and high-dose dexamethasone as per WHO guidelines\n* Signed informed consent form by patient or relative.\n\nExclusion Criteria:\n\n* Other concomitant neurological infection, i.e. toxoplasmosis, cryptococcosis, progressive multifocal leukoencephalopathy, bacterial meningitis, neuro-syphilis\n* Asymptomatic positive cryptococcal antigen in serum\n* HBsAg positive or anti hepatitis C virus antibodies positive\n* Alanine transaminase (ALT)\\>5 ULN\n* Rifampicin-resistant TB detected by GeneXpert MTB\u002FRIF Ultra\n* History of previous TB treatment in patients with GeneXpert MTB\u002FRIF Ultra negative or unavailable\n* Current use of drugs contraindicated with study drugs and that cannot be safely stopped\n* Allergy to study drugs or any of their components\n* Uncontrolled opportunistic infection\n* Moderate to severe cardiac insufficiency (NYHA classes III \u002F IV)\n* Any condition which might, in the investigator's opinion, compromise the safety of treatment and\u002For patient's adherence to study procedures\n* For women of childbearing age: 1) Pregnancy or breastfeeding; 2) Refusal to use effective contraception to be discussed with the investigator\n* Subjects participating in another clinical trial evaluating therapies and including an exclusion period that is still in force during the screening phase\n* Person under guardianship, or deprived of freedom by a judicial or administrative decision","ALL","18 Years",{"count":172,"type":173},130,"ESTIMATED","INTERVENTIONAL",[176],"PHASE2","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).",[179,180],"Tuberculous Meningitis","HIV I Infection","2025-12-08",{"date":183,"type":184},"2025-12-15","ACTUAL",{"date":186,"type":184},"2023-04-11",{"date":188,"type":173},"2027-12",{"name":5,"class":6},3]