Trial reportThe Journal of clinical investigation2021
Doxycycline host-directed therapy in human pulmonary tuberculosis.
Trial report in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 3 registered trials, which are not on this map. Cited by 47 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Doxycycline and the Modulation of Host Immunopathology in Human Pulmonary Tuberculosis: A Pilot Study
Doxycycline Host-directed Therapy to Improve Lung Function and Decrease Tissue Destruction in Pulmonary Tuberculosis: A Phase III Randomized Control Trial (Doxy-TB)
DIRECT: Doxycycline Adjunctive Therapy to Reduce Excess Mortality and Complications From Central Nervous System Tuberculosis - Phase II Randomized Clinical Trial
Who cites it
47 citing papers in PubMed, 75 citations in OpenAlex.
- Azithromycin as Host-Directed Therapy for Pulmonary Tuberculosis: A Randomized Pilot Trial.The Journal of infectious diseases · 2025Trial
- Proteomic Immune Signatures of Severe HIV-Associated Tuberculosis in Sub-Saharan Africa: A Prospective, Multicenter Analysis From Uganda.Critical care explorations · 2026Observational
- Interventions to reduce the impact of post-tuberculosis lung disease: a scoping review of the literature.BMC pulmonary medicine · 2026Article
- Towards host-directed therapy: The role of matrix metalloproteinases in the immunopathogenesis of tuberculosis.International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases · 2026Review
- Clinical and transcriptomic risk factors for post-tuberculosis lung disease in a cohort of Kenyan adults.American journal of respiratory and critical care medicine · 2026Observational
- Context-specific roles for IL-17 in tuberculosis.PLoS pathogens · 2026Review
- Post-TB lung disease: pathogenesis, host-directed therapies, and the C3HeB/FeJ model for pre-clinical advances.Infection and immunity · 2026Review
- Single-cell and spatial profiling highlights TB-induced myofibroblasts as drivers of lung pathology.The Journal of experimental medicine · 2026Article
- Albendazole-doxycycline combination therapy alleviates MRI- and pathology-evident neuroinflammation and restores IL-33/GFAP balance in mouse neuroangiostrongyliasis.Parasites & vectors · 2026Article
- Combinations of Favipiravir with Doxycycline, Azithromycin or Ivermectin Exert Synergistic Effects Against Influenza A H3N2 Virus Replication.Pathogens (Basel, Switzerland) · 2026Article
- MMPs and NETs are detrimental in CNS-tuberculosis with MMP Inhibition in CNS-tuberculosis mice improving survival.Journal of neuroinflammation · 2025Article
- Post-tuberculosis morbidities and their associated mortality: moving from challenges to solutions.European respiratory review : an official journal of the European Respiratory Society · 2025Review
- Matrix Metalloproteinase Inhibitors and Their Potential Clinical Application in Periodontitis.Diseases (Basel, Switzerland) · 2025Review
- Prospects of Inhalable Formulations of Conventionally Administered Repurposed Drugs for Adjunctive Treatment of Drug-Resistant Tuberculosis: Supporting Evidence from Clinical Trials and Cohort Studies.Journal of aerosol medicine and pulmonary drug delivery · 2025Review
- Collagen-targeted PET/CT imaging of tuberculosis patients.The European respiratory journal · 2025Article
- Post-tuberculosis lung disease: towards prevention, diagnosis, and care.The Lancet. Respiratory medicine · 2025Review
- Host-Directed Therapies Based on Protease Inhibitors to ControlMicroorganisms · 2025Review
- Host-directed therapy for tuberculosis.European journal of medical research · 2025Review
- Impact of doxycycline on mycoplasma pneumonia treatment and cancer prognosis in pediatric leukemia patients post-chemotherapy: a target trial emulation.American journal of cancer research · 2025Article
- Microenvironments of tuberculous granuloma: advances and opportunities for therapy.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
23 authors at 9 institutions in 2 countries.
Funding
Abstract
BACKGROUNDMatrix metalloproteinases (MMPs) are key regulators of tissue destruction in tuberculosis (TB) and may be targets for host-directed therapy. We conducted a phase II double-blind, randomized, controlled trial investigating doxycycline, a licensed broad-spectrum MMP inhibitor, in patients with pulmonary TB.METHODSThirty patients with pulmonary TB were enrolled within 7 days of initiating anti-TB treatment and randomly assigned to receive either 100 mg doxycycline or placebo twice a day for 14 days, in addition to standard care.RESULTSWhole blood RNA-sequencing demonstrated that doxycycline accelerated restoration of dysregulated gene expression in TB towards normality, rapidly down-regulating type I and II interferon and innate immune response genes, and up-regulating B-cell modules relative to placebo. The effects persisted for 6 weeks after doxycycline discontinuation, concurrent with suppressed plasma MMP-1. Doxycycline significantly reduced sputum MMP-1, -8, -9, -12 and -13, suppressed type I collagen and elastin destruction, reduced pulmonary cavity volume without altering sputum mycobacterial loads, and was safe.CONCLUSIONAdjunctive doxycycline with standard anti-TB treatment suppressed pathological MMPs in PTB patients. Larger studies on adjunctive doxycycline to limit TB immunopathology are merited.TRIAL REGISTRATIONClinicalTrials.gov NCT02774993.FUNDINGSingapore National Medical Research Council (NMRC/CNIG/1120/2014, NMRC/Seedfunding/0010/2014, NMRC/CISSP/2015/009a); the Singapore Infectious Diseases Initiative (SIDI/2013/013); National University Health System (PFFR-28 January 14, NUHSRO/2014/039/BSL3-SeedFunding/Jul/01); the Singapore Immunology Network Immunomonitoring platform (BMRC/IAF/311006, H16/99/b0/011, NRF2017_SISFP09); an ExxonMobil Research Fellowship, NUHS Clinician Scientist Program (NMRC/TA/0042/2015, CSAINV17nov014); the UK Medical Research Council (MR/P023754/1, MR/N006631/1); a NUS Postdoctoral Fellowship (NUHSRO/2017/073/PDF/03); The Royal Society Challenge Grant (CHG\R1\170084); the Sir Henry Dale Fellowship, Wellcome Trust (109377/Z/15/Z); and A*STAR.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.