Montelukast + rupatadine

Dengue can progress rapidly from a febrile illness to severe disease characterized by plasma leakage, shock, bleeding, and organ dysfunction. Although supportive fluid management can be lifesaving, there is no specific treatment that prevents disease progression. This project is developing an early host-directed treatment using two licensed oral medicines – rupatadine and montelukast – to target complementary inflammatory pathways involved in endothelial dysfunction and vascular leakage.

Rupatadine blocks platelet-activating factor and histamine receptors, while montelukast blocks the cysteinyl-leukotriene receptor. Previous clinical studies of each medicine used alone have shown acceptable safety and signals of biological or clinical activity. Pre-clinical studies indicate that combining the two drugs reduces vascular leakage and platelet activation more effectively than either medicine alone, supporting evaluation of the dual-pathway blockade.

The project will complete the translational, safety, dose, endpoint, regulatory, and operational evidence needed to determine whether the programme should proceed directly to a pivotal Phase III trial or first undertake a confirmatory Phase IIb study. The proposed clinical programme will evaluate early treatment in adults with laboratory-confirmed, non-severe dengue by assessing sustained clinical recovery, plasma leakage, warning signs, progression to severe dengue, hospitalization, and safety. Because both medicines are off-patent, orally administered, widely available, and potentially low-cost, a successful treatment could be rapidly scaled in dengue-endemic countries and help reduce complications, hospitalizations, and pressure on health systems.