Therapeutics for Moderate and Severe Dengue

NCT07543458 | Not Yet Recruiting Phase 3 DMC

• 2 other identifiers: OxTREC 3271082323061/Z/24/Z
• Study Type: interventional
• Target: 8,800
• Locations: 10 countries
• Sites: 18

Brief 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. 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.

Conditions

Dengue; Severe Dengue; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Flavivirus Infections; RNA Virus Infections; Hemorrhagic Fever

Keywords

dengue treatment; host-directed therapy; host-targeted therapeutics

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (10)

• Length of hospital stay

  At hospital discharge (average of 5 days)

• Lowest recorded platelet count

  Between randomisation and hospital discharge (average of 5 days)

• Acute kidney injury

  Between randomisation and hospital discharge (average of 5 days)

• Liver involvement

  Between randomisation and hospital discharge (average of 5 days)

• Change in ALT/AST

  at randomisation, day 2 (if feasible) and day 4 or hospital discharge (average on day 5) if sooner

Study Arms (3)

Comparison A: Baricitinib versus placebo

EXPERIMENTAL

Participants eligible for baricitinib may be randomized to baricitinib or matched placebo.

Drug: Placebo; Drug: Baricitinib

Comparison B: Dexamethasone versus Placebo

EXPERIMENTAL

Participants eligible for dexamethasone may be randomized to dexamethasone or matched placebo.

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.

Drug: N-Acetylcysteine; Other: Standard of care

Interventions

Placebo DRUG

Placebo matched to baricitinib/dexamethasone in form, dose, frequency and duration.

Comparison A: Baricitinib versus placebo; Comparison B: Dexamethasone versus Placebo

Dexamethasone DRUG

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.

Comparison B: Dexamethasone versus Placebo

N-Acetylcysteine DRUG

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.

Comparison C: N-acetylcysteine versus standard of care

Standard of care OTHER

Standard of care as per local site guidelines

Comparison C: N-acetylcysteine versus standard of care

Baricitinib DRUG

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.

Comparison A: Baricitinib versus placebo

Eligibility Criteria

• Age: 5 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• Pleural effusion or ascites on clinical or radiological examination
• Absolute haematocrit \>50%
• % 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)

You may not qualify if:

• A participant may not enter a specific treatment comparison if that treatment is considered to be indicated or contraindicated by the responsible clinician.

Sponsors & Collaborators

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

Study Sites (18)

Chittagong Medical College Hospital

Chittagong, Bangladesh

Location

Dhaka Medical College & Hospital

Dhaka, Bangladesh

Location

Dhaka North City Corporation Hospital

Dhaka, Bangladesh

Location

Instituto de Infectologia Emílio Ribas

São Paulo, Brazil

Location

Centro de Atención y Diagnóstico de Enfermedades Infecciosas

Bucaramanga, Colombia

Location

Fundación Valle del Lili

Cali, Colombia

Location

Hospital Universitario Erasmo Meoz

Cúcuta, Colombia

Location

Universitas Sumatera Utara

Medan, Indonesia

Location

Hospital Queen Elizabeth II, Sabah

Kota Kinabalu, Malaysia

Location

University Malaya Medical Centre

Kuala Lumpur, Malaysia

Location

National Academy of Medical Sciences/Bir Hospital

Kathmandu, Nepal

Location

Sukraraj Tropical and Infectious Disease Hospital

Kathmandu, Nepal

Location

Hospital Regional de Loreto

Iquitos, Peru

Location

San Lazaro Hospital

Manila, Philippines

Location

Siriraj Hospital, Mahidol University

Bangkok, Thailand

Location

Prince of Songkla University in Southern Thailand

Songkhla, Thailand

Location

Hospital for Tropical Diseases

Ho Chi Minh City, Vietnam

Location

Number 2 Children's Hospital

Ho Chi Minh City, Vietnam

Location

MeSH Terms

Conditions

Dengue; Severe Dengue; Mosquito-Borne Diseases; Vector Borne Diseases; Arbovirus Infections; Flavivirus Infections; RNA Virus Infections; Hemorrhagic Fevers, Viral

Interventions

Dexamethasone; Acetylcysteine; Standard of Care; baricitinib

Condition Hierarchy (Ancestors)

Infections; Virus Diseases; Flaviviridae Infections

Intervention Hierarchy (Ancestors)

Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins; Quality Indicators, Health Care; Quality of Health Care; Health Services Administration; Health Care Quality, Access, and Evaluation

Study Officials

• Sophie Yacoub, MD., PhD.

  University of Oxford, UK

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mr. Samuel Paul

CONTACT

den-host@ndm.ox.ac.uk

OUCRU-CTU

CONTACT

+84283924193; CTU-Wthics@oucru.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For placebo-matched agents, the participant, care provider, investigator and outcomes assessor will all be masked. Currently, this includes baricitinib and dexamethasone. The N-acetylcysteine arm is open-label with no masking; there will be no matched placebo. Treatment with N-acetylcysteine will be compared to standard care.
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: April 8, 2026
• First Posted: April 21, 2026
• Study Start (Estimated): October 1, 2026
• Primary Completion (Estimated): July 31, 2030
• Study Completion (Estimated): July 31, 2031
• Last Updated: April 21, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will share

Locations

BR (1); ID (1); MY (2); CO (3); VN (2); NE (2); PE (1); BA (3); TH (2); PH (1)