The DEN-HOST trial – a multi-site, placebo-controlled, randomised adaptive trial – is being delivered through a collaboration between the Pandemic Sciences Institute, the Programme for Research in Epidemic Preparedness and REsponse (PREPARE) under the Communicable Diseases Agency in Singapore, and the Oxford University Clinical Research Unit (OUCRU). It will initially involve trial sites in 10 countries across Asia and Latin America, where dengue is endemic and represents a major public health burden. The trial is funded by Wellcome, with support from PREPARE.
Dengue is a major and growing health problem. It is estimated that 40% of the world’s population live in dengue endemic areas. There are an estimated 105 million symptomatic dengue infections every year, and 40,000 deaths, with cases having increased tenfold over the past two decades. Although dengue vaccines offer some hope, it remains a leading cause of hospitalisation in affected regions, and there are currently no licensed antiviral or adjunctive therapies to treat the disease.
The DEN-HOST trial will initially test three promising treatments: baricitinib, dexamethasone, and N-acetylcysteine. The trial will assess whether these host-directed therapeutics can prevent disease progression and improve clinical outcomes for patients hospitalised with moderate-severe dengue. N-acetylcysteine will be trialled in a subgroup of patients with moderate or severe liver damage.
The rationale for the study builds on evidence that immunopathogenesis – the process by which a disease develops due to a harmful immune response – plays a key role in progression to severe dengue. Higher levels of inflammation at different stages of the disease have been shown to correlate with worsening symptoms and increased risk of death.
The trial will utilise the recently developed Dengue Core Outcome Set (DEN-CORE), which was an international consensus study by the same team aimed at harmonising outcomes across all dengue trials.
With a target enrolment of around 8,000 people, the DEN-HOST trial will be the largest study ever conducted for dengue therapeutics. It will build on established networks, including RECOVERY, ISARIC, PREPARE, and OUCRU.
Sophie Yacoub, Associate Professor of Infectious Diseases at PSI and chief investigator of the trial, said: “Our primary aim is to find safe and affordable therapeutics which prevent disease progression among those at high risk for severe dengue, and improve outcomes for those with established severe disease, thereby also reducing the substantial burden placed on health systems in dengue endemic regions.
"Through our extensive network of collaborators, the results of the DEN-HOST trial will have maximum impact and inform national and international guidelines for the clinical management of patients with dengue virus infection globally.”
Associate Professor Yeo Tsin Wen, Lead of the PREPARE Regional Networks Co-operative, said: “Dengue is a major problem in all ASEAN countries and there is currently no effective treatment. Hence, there was considerable interest from all our regional partners in the network to participate in the DEN-HOST trial.”
Chanh Ho Quang, DEN-Host trial lead at OUCRU-Vietnam, said: “In countries like Vietnam, dengue care has relied on supportive treatment for too long. The DEN-HOST trial is an important step toward active, evidence-based therapies. At OUCRU, we are proud to contribute to a collaboration that unites world-class science and regional commitment to transform how we manage and treat dengue”.
Sally Nicholas, Head of Vector Control and Therapeutics in Wellcome’s Infectious Disease team, said: “Dengue is a growing problem in many parts of the world, with rapidly rising cases fuelled by climate change, urbanisation and conflict. We urgently need a safe and effective treatment. This trial could transform dengue care – paving the way for more accessible, affordable life-saving therapies for those who need it most.”
The trial is expected to run for five years until 2031.