1. Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial
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Paradkar, Mandar S, D, Bella Devaleenal, Mvalo, Tisungane, Arenivas, Ana, Thakur, Kiran T, Wolf, Lisa, Nimkar, Smita, Inamdar, Sadaf, Giridharan, Prathiksha, Selladurai, Elilarasi, Kinikar, Aarti, Valvi, Chhaya, Khwaja, Saltanat, Gadama, Daphne, Balaji, Sarath, Kattagoni, Krishna Yadav, Venkatesan, Mythily, Savic, Radojka, Swaminathan, Soumya, Gupta, Amita, Gupte, Nikhil, Mave, Vidya, Dooley, Kelly E, Agiwal, Shivali, Ahire, Rupali, Balasubramanian, Usha, Bendre, Manjushree, Chandane, Jyoti, Chopade, Kavita, Dalimbkar, Shamala, Deshpande, Prasad, Dhage, Rajendra, Ithape, Mahesh, Jadhav, Varsha, Kante, Sonali, Kapre, Pallavi, Khan, Nawshaba, Kulkarni, Vandana, Madewar, Renu, Meshram, Shashibhushan, Muttha, Kunal, Nadgeri, Vaishali, Nagargoje, Arti, Nagraj, Amita, Nijampurkar, Aparna, Onawale, Prerana, Pawar, Namrata, Pawar, Prashant, Pradhan, Neeta, Shaikh, Varsha, Shaikh, Zaheda, Shere, Dhananjay, Wani, Gouri, Kulkarni, Rajesh, Rajput, Uday, Ganesan, Mangalambal, Arasan, Gunasundari, Shankar, Shakila, Mary, S Stella, Karuppaiah, Sureshwari, Pauline, Leema, Pramila, Snegha Karunakaran, Arul, Priyadharshini, Ganesh, Sankar, Hanna, Luke Elizabeth, Ramesh, K, Kannan, M, Vijayakumar, Ruthra, Sivakumar, Surekha S, Devika, K, Radhakrishnan, A, Preethi, AR, Rajkumar, S, Saravanan, N, Ramachandran, Geetha, Kumar, AK Hemanth, Dharman, M, Sudha, V, Hissar, Syed, Nagarajan, Valarmathi, Jennifer, Linda, Supriya, R, Manimegalai, R, Kandan, Santhanam, Maniselvi, Archana, Puspha, Oli, Vaishnavi, S, Selvi, R, Neelakandan, Logeswari, Chiunda, Mary, Chunga, Moreen, Kamanga, Madalo, Kamthunzi, Portia, Kanthiti, Elizabeth, Mbewe, Abineli, Msiska, Emmie, Mumba, Noel, Phiri, Ian Zifa, Palichina, Victor, and Sichali, Dorothy
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Pediatric ,Clinical Trials and Supportive Activities ,Clinical Research ,Evaluation of treatments and therapeutic interventions ,6.1 Pharmaceuticals ,Good Health and Well Being ,Adult ,Child ,Humans ,Rifampin ,Tuberculosis ,Meningeal ,Levofloxacin ,Ethambutol ,Antitubercular Agents ,Standard of Care ,pediatric tuberculous meningitis ,neuropsychological ,clinical trial ,levofloxacin ,high-dose rifampicin ,TuBerculous Meningitis in Kids (TBM-KIDS) Study Team ,Biological Sciences ,Medical and Health Sciences ,Microbiology - Abstract
BackgroundPediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM.MethodsTBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL).ResultsOf 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P
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- 2022