{"id":54207,"date":"2025-12-22T12:07:01","date_gmt":"2025-12-22T05:07:01","guid":{"rendered":"https:\/\/www.oucru.org\/?p=54207"},"modified":"2025-12-22T12:07:07","modified_gmt":"2025-12-22T05:07:07","slug":"no-survival-benefit-from-high-dose-rifampicin-in-tuberculous-meningitis-major-global-trial-finds","status":"publish","type":"post","link":"https:\/\/www.oucru.org\/vi\/no-survival-benefit-from-high-dose-rifampicin-in-tuberculous-meningitis-major-global-trial-finds\/","title":{"rendered":"No Survival Benefit from High-Dose Rifampicin in\u00a0Tuberculous Meningitis, Major Global Trial Finds\u00a0"},"content":{"rendered":"\n<p>A major international clinical trial, known as <a href=\"https:\/\/www.oucru.org\/project\/harvest-study\/\">the HARVEST trial,<\/a> has found that giving a higher dose of rifampicin does not improve survival in adults with tuberculous meningitis, the most severe and deadly form of tuberculosis.<\/p>\n\n\n\n<p>Tuberculous meningitis affects the brain and spinal cord and\u00a0remains\u00a0extremely difficult to treat. Up to half of patients die despite treatment, and many survivors are left with permanent neurological disability. One reason outcomes\u00a0remain\u00a0poor is that several standard TB drugs do not penetrate the brain well.<\/p>\n\n\n\n<p>The trial published last week in the\u00a0<a href=\"https:\/\/www.nejm.org\/doi\/full\/10.1056\/NEJMoa2502866\" target=\"_blank\" rel=\"noreferrer noopener\">New England Journal of Medicine<\/a>\u00a0found that patients who received a\u00a03.5-fold higher than standard\u00a0dose of rifampicin were not more likely to survive than those given the standard dose.<\/p>\n\n\n\n<figure class=\"wp-block-image size-large\"><a href=\"https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-scaled.jpeg\"><img fetchpriority=\"high\" decoding=\"async\" width=\"1024\" height=\"683\" src=\"https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-1024x683.jpeg\" alt=\"\" class=\"wp-image-54212\" srcset=\"https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-1024x683.jpeg 1024w, https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-300x200.jpeg 300w, https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-768x512.jpeg 768w, https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-1536x1024.jpeg 1536w, https:\/\/www.oucru.org\/wp-content\/uploads\/2025\/12\/DSC00247_resized-2048x1365.jpeg 2048w\" sizes=\"(max-width: 1024px) 100vw, 1024px\" \/><\/a><figcaption class=\"wp-element-caption\">A laboratory technician prepares a patient sample for GeneXpert testing, a rapid molecular test used to help diagnose tuberculous meningitis. Photo credit: OUCRU Indonesia.<\/figcaption><\/figure>\n\n\n\n<p>After six months of follow-up, 44.6 percent in the high-dose rifampicin group had died, compared with 40.7 percent in the standard-dose group, a difference that was not statistically significant.\u00a0Patients receiving the higher dose also recovered consciousness more slowly, and no improvement was seen in disability or longer-term neurological outcomes.<\/p>\n\n\n\n<p>For more than a decade, researchers have explored whether increasing the dose of rifampicin could improve outcomes. Earlier, smaller studies in Indonesia, South Africa, and Uganda showed that higher doses could safely raise drug levels in the blood and spinal fluid.<\/p>\n\n\n\n<p><a href=\"https:\/\/www.oucru.org\/project\/harvest-study\/\" target=\"_blank\" rel=\"noreferrer noopener\">The HARVEST trial<\/a>\u00a0was designed to test whether this strategy could translate into better survival,\u00a0and\u00a0is the largest and most rigorous evaluation to date of intensified rifampicin therapy for TB meningitis.<\/p>\n\n\n\n<p>The trial enrolled 499 adults with tuberculous meningitis across nine hospitals in Indonesia, South Africa, and Uganda. Around 60 percent of participants were living with HIV, and most had severe disease at the time of enrolment.<\/p>\n\n\n\n<p>Patients were randomly assigned to receive either a high dose of rifampicin (35 mg per kilogram per day), or the standard dose (10 mg per kilogram per day)\u00a0during the first eight weeks of treatment. All patients also received other standard TB drugs and corticosteroids.<\/p>\n\n\n\n<p>Researchers believe the worse early outcomes may be linked to an excessive inflammatory response in the brain when TB bacteria are killed more rapidly. In tuberculous meningitis, inflammation itself can be life-threatening and may outweigh any potential benefit of higher antibiotic drug exposure.<\/p>\n\n\n\n<p>In Indonesia, the trial was conducted at <a href=\"https:\/\/web.rshs.go.id\/\">Hasan\u00a0Sadikin<\/a>,\u00a0<a href=\"https:\/\/rsudcibabat.cimahikota.go.id\/\">Cibabat<\/a>, and <a href=\"https:\/\/www.rsimmanuel.com\/\">Immanuel<\/a> Hospitals in Bandung, as well as in <a href=\"https:\/\/ciptomangunkusumo.id\/\">Dr.\u00a0Cipto\u00a0Mangunkusumo<\/a> and the <a href=\"http:\/\/rumahsakitpolrikramatjati.co.id\/\">Indonesia Police<\/a> Hospitals in Jakarta. It involved researchers from <a href=\"http:\/\/fk.ui.ac.id\">the Faculty of Medicine Universitas Indonesia <\/a>and <a href=\"https:\/\/fk.unpad.ac.id\/\">the Faculty of Medicine Universitas\u00a0Padjadjaran<\/a>.<\/p>\n\n\n\n<p>\u201cThe findings provide essential direction for the global TB research community,\u201d said\u00a0<a href=\"https:\/\/imeri.fk.ui.ac.id\/research-clusters\/neuroscience-and-brain-development\/\" target=\"_blank\" rel=\"noreferrer noopener\">Dr Darma Imran<\/a>, a neurologist and Principal Investigator at\u00a0Cipto\u00a0Mangunkusumo\u00a0Hospital and a researcher at the Faculty of Medicine Universitas Indonesia. \u201cThese results help doctors avoid treatments that add risk without benefit, and they add to the evidence needed to improve care for patients with tuberculous meningitis.\u201d<\/p>\n\n\n\n<p>\u201cThis trial is also a win for Indonesia,\u201d said\u00a0<a href=\"https:\/\/www.oucru.org\/people\/associate-professor-raph-hamers\/\" target=\"_blank\" rel=\"noreferrer noopener\">Prof Raph Hamers<\/a>, one of the trial investigators based at OUCRU Indonesia.\u00a0\u201cDespite the disappointing clinical outcome, HARVEST\u00a0demonstrates\u00a0that complex, rigorous randomised clinical trials can be successfully conducted here, through collaboration with international partners. We\u00a0hope that this trial will galvanize renewed global attention for this neglected, highly fatal disease, exploring strengthened anti-inflammatory treatments, more sensitive diagnostics, enabling earlier intervention, and enhanced supportive care.\u201d<\/p>\n\n\n\n<p>The researchers stress that these findings apply specifically to tuberculous meningitis and should not be generalised to pulmonary TB or other forms of tuberculosis, where drug penetration and immune responses are\u00a0very different.<\/p>\n\n\n\n<p>The study was led by <a href=\"https:\/\/som.mak.ac.ug\/our_team\/dr-meya-david\/\">Professor David Meya<\/a> of the Infectious Diseases Institute, Makerere University in Uganda, and <a href=\"https:\/\/fk.unpad.ac.id\/prof-rovina-ruslami-dr-sppd-phd\/\">Professor Rovina\u00a0Ruslami<\/a>\u00a0of Universitas\u00a0Padjadjaran\u00a0in Bandung, Indonesia. Other collaborators were from <a href=\"https:\/\/www.radboudumc.nl\/en\/patient-care\">Radboud University Medical\u00a0Center<\/a>\u00a0in the Netherlands and the <a href=\"https:\/\/twin-cities.umn.edu\/\">University of Minnesota<\/a> in the United States. The trial was funded by the <a href=\"https:\/\/www.ukri.org\/councils\/mrc\/\">UK Medical Research Council<\/a> through the Joint Global Health Trials scheme.<\/p>\n\n\n\n<p><\/p>\n","protected":false},"excerpt":{"rendered":"<p>A major international clinical trial, known as the HARVEST trial, has found that giving a higher dose of rifampicin does not improve survival in adults with tuberculous meningitis, the most [&hellip;]<\/p>\n","protected":false},"author":42,"featured_media":54208,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_links_to":"","_links_to_target":"","_wp_rev_ctl_limit":""},"categories":[146],"tags":[],"class_list":["post-54207","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-indonesia"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v25.3.1 - https:\/\/yoast.com\/wordpress\/plugins\/seo\/ -->\n<title>No Survival Benefit from High-Dose Rifampicin in\u00a0Tuberculous Meningitis, Major Global Trial Finds\u00a0 - 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