DenguePhase 3DEN-HOSTNCT07543458
Therapeutics for Moderate and Severe Dengue
A Phase 3 study testing Dexamethasone, N-Acetylcysteine and Baricitinib in people with Dengue and Severe Dengue, run by Oxford University Clinical Research Unit, Vietnam at 18 sites in 10 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 5 years and older
- Conditions the study is for
- Dengue, Severe Dengue, Mosquito-Borne Diseases
- What is being tested?
- Dexamethasone, N-Acetylcysteine and Baricitinib
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 8,800 participants
- Where
- 18 sitesin 10 countries
- Study dates
- 1 Oct 2026to 31 Jul 2031
- Phase
- Phase 3
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 5 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Age ≥5 years
- Decision to hospitalise
- Clinical diagnosis of dengue
- Participants must also have at least one of the following:
- Severe abdominal pain or tenderness
- Vomiting more than 3 times in the past 24 hours
Show all 16Show fewer
- Pleural effusion or ascites on clinical or radiological examination
- Absolute haematocrit >50%
- 15% increase in haematocrit compared with a baseline sample (defined as the first sample taken during the current illness)
- Absolute platelet count <50 × 10⁹/L
- Absolute platelet count <100 × 10⁹/L AND a drop >50 × 10⁹/L in the past 32 hours
- ALT or AST >400 IU/L
- 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
- Bleeding leading to hypotension for age or requiring blood transfusion or medical intervention (e.g. surgery, endoscopy, or vasoactive drugs)
- Symptomatic bleeding into a critical site (intracranial, intraspinal, intraocular with visual impairment, retroperitoneal, intra-articular, pericardial, or intramuscular with compartment syndrome)
- 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
Who cannot join
- 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.
Trial locations and contacts
18 sites in 10 countries. Contact the study team or a site near you to ask about taking part.
Mr. Samuel Paul contact
18 sites in 10 countries
Bangladesh3 sites
Chittagong Medical College Hospital
Chittagong
Aniruddha Ghose, Prof, anrdghs@yahoo.com
Dhaka Medical College & Hospital
Dhaka
Md. Jobayer Chisti, MD, chisti@icddrb.org,
Lubaba Shahrin, MD, lubabashahrin@icddrb.org
Dhaka North City Corporation Hospital
Dhaka
Lubaba Shahrin, MD, lubabashahrin@icddrb.org
Colombia3 sites
Centro de Atención y Diagnóstico de Enfermedades Infecciosas
Bucaramanga
Luis A Villar, MD, direccioninvestigacion@cdi.net.co
Fundación Valle del Lili
Cali
Carlos Cotes, MD, centrodeinvestigaciones@fvl.org.co
Hospital Universitario Erasmo Meoz
Cúcuta
Malaysia2 sites
Hospital Queen Elizabeth II, Sabah
Kota Kinabalu
Giri Rajaharam, MD, gsrajahram@gmail.com
University Malaya Medical Centre
Kuala Lumpur
Mohad Shahnaz Hasan, MD
Ong Hang-Cheng, MD, ong.hc@ummc.edu.my
Nepal2 sites
National Academy of Medical Sciences/Bir Hospital
Kathmandu
Sudeep Adhikari, MD, sadhikari@oucru.org
Sukraraj Tropical and Infectious Disease Hospital
Kathmandu
Sudeep Adhikari, MD, sadhikari@oucru.org
Thailand2 sites
Siriraj Hospital, Mahidol University
Bangkok
Nasikarn Angkasekwinai, MD, nasikarn@gmail.com
Panisadee Avirutnan, MD
Prince of Songkla University in Southern Thailand
Songkhla
Nasikarn Angkasekwinai, MD, nasikarn@gmail.com
Vietnam2 sites
Hospital for Tropical Diseases
Ho Chi Minh City
Dung Thanh Nguyen, MD
Trung Ngoc Truong, MD, drngoctrung2984@gmail.com
Number 2 Children's Hospital
Ho Chi Minh City
Tung Huu Trinh, MD
Qui Dinh Nguyen, MD
Brazil1 site
Instituto de Infectologia Emílio Ribas
São Paulo
Claudia Figueiredo Mello, MD, claudia.mello@emilioribas.sp.gov.br
Indonesia1 site
Universitas Sumatera Utara
Medan
Inke Nadia Diniyanti Lubis, MD, inke.nadia@usu.ac.id
Peru1 site
Hospital Regional de Loreto
Iquitos
Juan Carlos Celis Salinas, MD, gipeit@gmail.com
Philippines1 site
San Lazaro Hospital
Manila
Ana Ria Sayo, MD, sayoanaria@gmail.com
About this study
Official title: 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.
Read the 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.
- Conditions
- Dengue, Severe Dengue, Mosquito-Borne Diseases, Vector Borne Diseases, Arbovirus Infections, Flavivirus Infections
- Being tested
- Placebo, Dexamethasone, N-Acetylcysteine, Standard of care, Baricitinib
- Keywords
- dengue treatment, host-directed therapy, host-targeted therapeutics
- Medical subject headings
- Dengue, Severe Dengue, Mosquito-Borne Diseases, Vector Borne Diseases, Arbovirus Infections, Flavivirus Infections, RNA Virus Infections, Hemorrhagic Fevers, Viral
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PlaceboDrug
Placebo matched to baricitinib/dexamethasone in form, dose, frequency and duration.
DexamethasoneDrug
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.
N-AcetylcysteineDrug
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.
Standard of careOther
Standard of care as per local site guidelines
BaricitinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Comparison A: Baricitinib versus placebo | Experimental | Participants eligible for baricitinib may be randomized to baricitinib or matched placebo. Receives: Drug: Placebo; Drug: Baricitinib |
| Comparison B: Dexamethasone versus Placebo | Experimental | Participants eligible for dexamethasone may be randomized to dexamethasone or matched placebo. Receives: Drug: Placebo; Drug: Dexamethasone |
| Comparison C: N-acetylcysteine versus standard of care | Experimental | Patients with liver involvement (ALT or AST >400 IU/L) during hospital admission may be randomised to N-acetylcysteine or standard of care. Receives: Drug: N-Acetylcysteine; Other: Standard of care |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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
Measured: Day 30
Secondary outcomes (10)
Length of hospital stay
Number of days from hospital admission to discharge
Measured: At hospital discharge (average of 5 days)
Lowest recorded platelet count
Lowest recorded platelet count between randomisation and hospital discharge
Measured: Between randomisation and hospital discharge (average of 5 days)
Acute kidney injury
Serum creatinine > 3.5 mg/dL or more than double baseline
Measured: Between randomisation and hospital discharge (average of 5 days)
Liver involvement
Highest recorded ALT or AST
Measured: Between randomisation and hospital discharge (average of 5 days)
Change in ALT/AST
N-acetylcysteine treatment comparison only. Fold change in ALT or AST
Measured: 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
Measured: Between randomisation and hospital discharge (average of 5 days)
Highest INR
N-acetylcysteine treatment comparison only. Highest recorded INR
Measured: Between randomisation and hospital discharge (average of 5 days)
Safety reporting: Suspected Severe Adverse Reactions
Suspected serious adverse reactions (SSARs) excluding primary outcomes
Measured: 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).
Measured: 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.
Measured: at day 30 follow up
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Apr 2026
- Study start1 Oct 2026 (estimated)
- Primary completion31 Jul 2030 (estimated)
- Study completion31 Jul 2031 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DengueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Factorial
- Model description
- This multi-site, phase 3, randomised, clinical trial will evaluate therapeutic agents in patients hospitalised with moderate or severe dengue virus infection. The trial will employ partial factorial randomisation. 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. Patients are randomised to Baricitinib versus placebo (Comparison A) and/or Dexamethasone versus placebo (Comparison B) depending on eligibility. Participants who are ineligible for one intervention are randomized only to the other intervention. In addition, participants with evidence of liver involvement undergo a second, independent randomisation to receive N-acetylcysteine or standard of care (Comparison C). This second randomisation may occur at any time during admission, when the patient is first noted to fulfil the eligibility criteria during the main trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 8,800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oxford University Clinical Research Unit, Vietnam
- Sponsor type
- University, hospital or other
- Collaborators
- University of Oxford, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, Number 2 Children's Hospital, Ho Chi Minh City, Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Nepal, National Academy of Medical Sciences/Bir Hospital, Kathmandu, Nepal, Siriraj Hospital, Prince of Songkla University in Southern Thailand, Thailand, Dhaka Medical College, Chittagong Medical College and Hospital, 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, Universitas Airlangga, University of Malaya, Hospital Queen Elizabeth, Malaysia, San Lazaro Hospital (SLH-NU), Manila, Philippines
- Responsible party
- Sponsor
- Investigators
- Sophie Yacoub, MD., PhD., Principal investigator, University of Oxford, UK
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07543458
- Sponsor's protocol ID
- OxTREC 3271082
- Other IDs
- 323061/Z/24/Z
- Acronym
- DEN-HOST
- Status last verified
- Apr 2026
- First submitted
- 8 Apr 2026
- Last updated
- 21 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.