Therapeutics for Moderate and Severe Dengue (DEN-HOST)

A Randomised Platform Trial to Evaluate Therapeutics in Patients With Moderate or Severe Dengue (DEN-HOST)

The purpose of this multi-site, factorial randomised, platform trial is to evaluate host-directed therapeutic agents in patients hospitalised with moderate and severe dengue virus infection. 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.

Study Overview

• Status: Not yet recruiting
• Conditions: RNA Virus Infections; Arbovirus Infections; Vector Borne Diseases; Flavivirus Infections; Dengue; Severe Dengue; Hemorrhagic Fever; Mosquito-Borne Diseases
• Intervention / Treatment: Drug: Placebo; Drug: Baricitinib; Drug: Dexamethasone; Drug: N-Acetylcysteine; Other: Standard of care

Detailed Description

This multi-site, factorial randomised, platform clinical trial will evaluate host-directed therapeutic agents in patients hospitalised with moderate and severe dengue virus infection. The 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.

The trial will employ partial factorial randomization. Participants who provide informed consent will be entered into one or more randomisations, depending on eligibility for each intervention, clinician discretion, and availability of the treatment at the study site. For each intervention, eligible participants will be randomised in a 1:1 ratio to receive either the active intervention or the corresponding control (either matched placebo or usual care, depending on the intervention). Participants who are ineligible for a specific treatment comparison may still enter other treatment comparisons within the trial.

Outcomes are described in more detail in the outcome section below. Participants will be followed up until death/day 30 after randomisation (whichever is sooner) to monitor for primary, secondary and safety outcomes. Participants who have been discharged from hospital alive before day 30 will have a final assessment conducted by telephone at least 30 days after randomisation.

Patients will be additionally consented for collection of a blood sample, taken and stored as a dried blood spot, for analyses in genetic studies and other research.

• Study Type: Interventional
• Enrollment (Estimated): 8800
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Mr. Samuel Paul; Email: den-host@ndm.ox.ac.uk
• Study Contact Backup: Name: OUCRU-CTU; Phone Number: +84283924193; Email: CTU-Wthics@oucru.org

Study Locations

• Bangladesh
  • Chittagong, Bangladesh
    • Chittagong medical College hospital
    • Contact: Aniruddha Ghose, Prof; Email: anrdghs@yahoo.com
  • Dhaka, Bangladesh
    • Dhaka Medical College & Hospital
    • Contact: Md. Jobayer Chisti, MD; Email: chisti@icddrb.org,
    • Contact: Lubaba Shahrin, MD; Email: lubabashahrin@icddrb.org
  • Dhaka, Bangladesh
    • Dhaka North City Corporation Hospital
    • Contact: Lubaba Shahrin, MD; Email: lubabashahrin@icddrb.org
• Brazil
  • São Paulo, Brazil
    • Instituto de Infectologia Emilio Ribas
    • Contact: Claudia Figueiredo Mello, MD; Email: claudia.mello@emilioribas.sp.gov.br
• Colombia
  • Bucaramanga, Colombia
    • Centro de Atención y Diagnóstico de Enfermedades Infecciosas
    • Contact: Luis A Villar, MD; Email: direccioninvestigacion@cdi.net.co
  • Cali, Colombia
    • Fundacion Valle del Lili
    • Contact: Carlos Cotes, MD; Email: centrodeinvestigaciones@fvl.org.co
  • Cúcuta, Colombia
    • Hospital Universitario Erasmo Meoz
• Indonesia
  • Medan, Indonesia
    • Universitas Sumatera Utara
    • Contact: Inke Nadia Diniyanti Lubis, MD; Email: inke.nadia@usu.ac.id
• Malaysia
  • Kota Kinabalu, Malaysia
    • Hospital Queen Elizabeth II, Sabah
    • Contact: Giri Rajaharam, MD; Email: gsrajahram@gmail.com
  • Kuala Lumpur, Malaysia
    • University Malaya Medical Centre
    • Contact: Mohad Shahnaz Hasan, MD
    • Contact: Ong Hang-Cheng, MD; Email: ong.hc@ummc.edu.my
• Nepal
  • Kathmandu, Nepal
    • National Academy of Medical Sciences/Bir Hospital
    • Contact: Sudeep Adhikari, MD; Email: sadhikari@oucru.org
  • Kathmandu, Nepal
    • Sukraraj Tropical and Infectious Disease Hospital
    • Contact: Sudeep Adhikari, MD; Email: sadhikari@oucru.org
• Peru
  • Iquitos, Peru
    • Hospital Regional de Loreto
    • Contact: Juan Carlos Celis Salinas, MD; Email: gipeit@gmail.com
• Philippines
  • Manila, Philippines
    • San Lazaro Hospital
    • Contact: Ana Ria Sayo, MD; Email: sayoanaria@gmail.com
• Thailand
  • Bangkok, Thailand
    • Siriraj Hospital, Mahidol University
    • Contact: Nasikarn Angkasekwinai, MD; Email: nasikarn@gmail.com
    • Contact: Panisadee Avirutnan, MD
  • Songkhla, Thailand
    • Prince of Songkla University in Southern Thailand
    • Contact: Nasikarn Angkasekwinai, MD; Email: nasikarn@gmail.com
• Vietnam
  • Ho Chi Minh City, Vietnam
    • Hospital For Tropical Diseases
    • Contact: Dung Thanh Nguyen, MD
    • Contact: Trung Ngoc Truong, MD; Email: drngoctrung2984@gmail.com
    • Sub-Investigator: Trung Ngoc Truong, MD
  • Ho Chi Minh City, Vietnam
    • Number 2 Children's Hospital
    • Contact: Tung Huu Trinh, MD
    • Sub-Investigator: Qui Dinh Nguyen, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age ≥5 years
• Decision to hospitalise
• Clinical diagnosis of dengue

• Participants must also have at least one of the following:

  1. Severe abdominal pain or tenderness
  2. Vomiting more than 3 times in the past 24 hours
  3. Pleural effusion or ascites on clinical or radiological examination
  4. Absolute haematocrit >50%
  5. 15% increase in haematocrit compared with a baseline sample (defined as the first sample taken during the current illness)
  6. Absolute platelet count <50 × 10⁹/L
  7. Absolute platelet count <100 × 10⁹/L AND a drop >50 × 10⁹/L in the past 32 hours
  8. ALT or AST >400 IU/L
  9. Pulse pressure <20mmHg or hypotension for age AND at least one of: peripheral capillary refill time >2 seconds; urine output 0.5ml/kg/hr; cold/clammy peripheries; agitation or altered mental state
  10. Bleeding leading to hypotension for age or requiring blood transfusion or medical intervention (e.g. surgery, endoscopy, or vasoactive drugs)
  11. Symptomatic bleeding into a critical site (intracranial, intraspinal, intraocular with visual impairment, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome)
  12. Requirement for organ support, including vasopressors or inotropes, assisted ventilation, dialysis or haemofiltration, or coma (unresponsive to pain without sedation) or requirement for intravenous antiseizure medications

Exclusion Criteria:

• Patients on ≥ day 10 of illness or who are clinically improving in the opinion of the managing doctor (the 'recovery phase') will be excluded from recruitment. Other exclusion criteria are specific to individual treatment comparisons, and do not preclude randomisation to other arms of the study.
• A participant may not enter a specific treatment comparison if that treatment is considered to be indicated or contraindicated by the responsible clinician.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Quadruple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Comparison A: Baricitinib versus placebo; Participants eligible for baricitinib may be randomized to baricitinib or matched placebo.	Drug: Placebo; Placebo matched to baricitinib/dexamethasone in form, dose, frequency and duration.; Drug: Baricitinib; Baricitinib is an inhibitor of Janus Kinase (JAK) 1 & 2, and Numb associated kinase (NAK). Form: tablet. Dose: Aged ≥ 12 years: 4mg once daily, Aged 5 - 11 years: 2mg once daily. - Renal adjustment of dose: Adults: eGFR ≥30 and <60 mL/min/1.73m2: 2mg once daily, eGFR ≥15 and <30 mL/min/1.73m2: 2mg on alternate days. Children: eGFR ≥30 and <60mL/min/1.73m2: 2mg on alternate days - Dose should be halved in patients also taking probenecid Duration: 4 days, or less if the patient is discharged before this time.
Experimental: Comparison B: Dexamethasone versus Placebo; Participants eligible for dexamethasone may be randomized to dexamethasone or matched placebo.	Drug: Placebo; Placebo matched to baricitinib/dexamethasone in form, dose, frequency and duration.; Drug: Dexamethasone; Dexamethasone is a corticosteroid. Form: tablet or intravenous preparation. Dose: Aged ≥ 12 years: 6mg once daily. Aged 5 - 11 years by weight: 10kg to <20 kg: 2mg once daily,; 20kg to <30 kg: 4mg once daily,; 30kg: 6mg once daily. Duration: 4 days, or until discharge if this happens before.
Experimental: Comparison C: N-acetylcysteine versus standard of care; Patients with liver involvement (ALT or AST >400 IU/L) during hospital admission may be randomised to N-acetylcysteine or standard of care.	Drug: N-Acetylcysteine; N-acetylcysteine acts to protect the liver. It functions as a glutathione precursor and antioxidant. Dose: 100mg/kg/day, by continuous infusion over 24 hours in glucose 5% (preferred) or sodium chloride 0.9%. Duration: 4 days, or until hospital discharge if sooner.; Other: Standard of care; Standard of care as per local site guidelines

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression to severe dengue/critical dengue	In the trial, baseline severity of dengue will be assessed at the start of study participation. Participants will be defined in accordance with our case definitions as having moderate, severe or critical dengue, based on clinical signs and symptoms, laboratory parameters, and if they have evidence of organ failure with or without need for organ support. At hospital discharge or following death, we will capture if the participant had evidence of at least one of: Progression to Severe dengue, in a participant with moderate dengue at enrolment,; Progression to Critical dengue, in a participant with moderate or severe dengue at enrolment.	between randomization to hospital discharge (average of 5 days)
All-cause mortality within 30 days	All-cause mortality in any participant. Assessed as dead or alive	Day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Length of hospital stay	Number of days from hospital admission to discharge	At hospital discharge (average of 5 days)
Lowest recorded platelet count	Lowest recorded platelet count between randomisation and hospital discharge	Between randomisation and hospital discharge (average of 5 days)
Acute kidney injury	Serum creatinine > 3.5 mg/dL or more than double baseline	Between randomisation and hospital discharge (average of 5 days)
Liver involvement	Highest recorded ALT or AST	Between randomisation and hospital discharge (average of 5 days)
Change in ALT/AST	N-acetylcysteine treatment comparison only. Fold change in ALT or AST	at randomisation, day 2 (if feasible) and day 4 or hospital discharge (average on day 5) if sooner
Highest bilirubin	N-acetylcysteine treatment comparison only. Highest recorded bilirubin	Between randomisation and hospital discharge (average of 5 days)
Highest INR	N-acetylcysteine treatment comparison only. Highest recorded INR	Between randomisation and hospital discharge (average of 5 days)
Safety reporting: Suspected Severe Adverse Reactions	Suspected serious adverse reactions (SSARs) excluding primary outcomes	During hospital stay (average of 5 days) and at day 30 follow up
Quality of live assessment using EQ-5D-5L value index	The EQ-5D-5L (EuroQoL [European Quality of Life] 5-Dimension 5-Level) is a standardized measure of health-related quality of life assessing five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain is self-reported by the respondent and rated on five levels of severity, ranging from "no problems" (level 1) to "extreme problems/unable" (level 5). Responses across the five domains define a health state, which is converted into a single index (utility) score using population-based value sets. This index score typically ranges from values below 0 (health states considered worse than death) to 1 (perfect health).	at day 30 follow up
Quality of live assessment using EQ-Visual Analogue Scale (VAS)	This is a self-rated measure of overall health. Respondent indicate their current health status on a vertical scale from 0 to 100. A score of 0 represents "the worst health you can imagine" and 100 represents "the best health you can imagine". This measure captures the respondent's subjective assessment of their overall health on the day of evaluation. When this assessment done remotely by telephone, the rating is approximated verbally by the respondent using the 0 to 100 numeric scale.	at day 30 follow up

Collaborators and Investigators

• Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: University of Oxford; Siriraj Hospital; Number 2 Children's Hospital, Ho Chi Minh City; The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam; Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Nepal; National Academy of Medical Sciences/Bir Hospital, Kathmandu, Nepal; Prince of Songkla University in Southern Thailand, Thailand; Dhaka Medical College & Hospital, Dhaka, Bangladesh; Chittagong Medical College Hospital, Chittagong, Bangladesh; Centro de Atención y Diagnóstico de Enfermedades Infecciosas, Bucaramanga, Colombia; Hospital Universitario Erasmo Meoz, Cucuta, Colombia; Fundación Valle del Lili, Cali, Colombia; Hospital Regional de Loreto, Iquitos, Peru; Instituto de Infectologia Emílio Ribas, São Paulo, Brazil; Universitas Sumatera Utara, Medan, Indonesia; Airlangga University (UNAIR), Indonesia; University Malaya Medical Centre, Malaysia; Hospital Queen Elizabeth II, Malaysia; San Lazaro Hospital (SLH-NU), Manila, Philippines
• Investigators: Principal Investigator: Sophie Yacoub, MD., PhD., University of Oxford, UK

Study record dates

Study Major Dates

• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2031

Study Registration Dates

• First Submitted: April 8, 2026
• First Submitted That Met QC Criteria: April 15, 2026
• First Posted (Actual): April 21, 2026

Study Record Updates

• Last Update Posted (Actual): April 21, 2026
• Last Update Submitted That Met QC Criteria: April 15, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: dengue treatment; host-directed therapy; host-targeted therapeutics
• Additional Relevant MeSH Terms: Infections; Virus Diseases; Flaviviridae Infections; Vector Borne Diseases; Mosquito-Borne Diseases; Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Flavivirus Infections; RNA Virus Infections; Arbovirus Infections; Health Services Administration; Health Care Quality, Access, and Evaluation; Amino Acids, Peptides, and Proteins; Sulfur Compounds; Organic Chemicals; Quality of Health Care; Polycyclic Compounds; Quality Indicators, Health Care; Amino Acids; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pregnadienetriols; Cysteine; Amino Acids, Sulfur; Dexamethasone; Acetylcysteine; Standard of Care; baricitinib
• Other Study ID Numbers: OxTREC 3271082; 323061/Z/24/Z (Other Grant/Funding Number: Wellcome)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: With ethical approval and patient consent, the database may be shared with researchers not directly involved in this study but only after the main paper has been published and in accordance with local and national policies. The database will only be shared if future publications are not compromised. No identifiable information will be shared with any other person/organisation than that authorised in the protocol.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No