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Adjunctive Doxycycline for Central Nervous System Tuberculosis
Sponsor: National University Hospital, Singapore
Summary
Although tuberculosis is now considered a treatable disease, central nervous system tuberculosis (CNS-TB) when managed with the current standard-of-care (SOC), still has mortality rates ranging from 30-50% even in tertiary hospital centers. At present, the SOC for the management of CNS-TB is anti-tuberculous therapy with adjunctive corticosteroids. In CNS-TB, the activity of pathogenic host matrix metalloproteinases (MMPs) is unopposed to tissue inhibitors of metalloproteinases (TIMPs), resulting in a matrix-degrading phenotype which may drive worse outcomes in CNS-TB. In a prior established CNS-TB murine model, the investigators have demonstrated that adjunctive MMP inhibition using doxycycline, a widely available and cheap drug, in addition to standard TB treatment, compared with standard TB treatment alone, improved murine survival (Manuscript in preparation). The investigators previously showed that in humans with pulmonary TB, doxycycline with anti-TB treatment is safe, accelerates the resolution of inflammation, and suppresses systemic and respiratory MMPs. Hence, the investigators are now ideally positioned to determine if adjunctive doxycycline in patients with CNS-TB can improve clinical outcomes. The investigators will perform a Phase 2 double-blind randomized-controlled trial (RCT) of adjunctive doxycycline versus placebo with standard TB treatment and steroids for 8 weeks, with the primary outcome of 8-week mortality or severe neurological deficits.
Official title: DIRECT: Doxycycline Adjunctive Therapy to Reduce Excess Mortality and Complications From Central Nervous System Tuberculosis - Phase II Randomized Clinical Trial
Key Details
Gender
All
Age Range
21 Years - Any
Study Type
INTERVENTIONAL
Enrollment
200
Start Date
2025-08-21
Completion Date
2027-12
Last Updated
2025-08-27
Healthy Volunteers
No
Conditions
Interventions
Doxycycline
adjunctive doxycycline to standard anti-tuberculous treatment and corticosteroid therapy
Placebo
Placebo
Anti Tuberculosis Drug
Standard anti-tuberculous therapy
Adjunctive corticosteroid
Adjunctive corticosteroids to be dosed at 0.4mg/kg/day of dexamethasone or equivalent for week 1, then 0.3mg/kg/day for week 2, 0.2mg/kg/day for week 3, 0.1mg/kg/day for week 4, then tapered to stop over the next 4 weeks. Other forms of corticosteroids are also acceptable eg. hydrocortisone, methylprednisolone at the equivalent dosage
Locations (5)
Adam Malik Hospital
Medan, Indonesia
Universitas Sumatera Utara
Medan, Indonesia
Sarawak General Hospital
Kuching, Sarawak, Malaysia
National University Hospital
Singapore, Singapore
Tan Tock Seng Hospital
Singapore, Singapore