Therapeutics for Moderate and Severe Dengue

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

Interventions

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.

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

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.

Sponsors & Collaborators

• University of Oxford

  collaborator OTHER

• The Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

  collaborator UNKNOWN

• Number 2 Children's Hospital, Ho Chi Minh City

  collaborator OTHER

• Sukraraj Tropical and Infectious Disease Hospital, Kathmandu, Nepal

  collaborator UNKNOWN

• National Academy of Medical Sciences/Bir Hospital, Kathmandu, Nepal

  collaborator UNKNOWN

• Siriraj Hospital

  collaborator OTHER

• Prince of Songkla University in Southern Thailand, Thailand

  collaborator UNKNOWN

• Dhaka Medical College & Hospital, Dhaka, Bangladesh

  collaborator UNKNOWN

• Chittagong Medical College Hospital, Chittagong, Bangladesh

  collaborator UNKNOWN

• Centro de Atención y Diagnóstico de Enfermedades Infecciosas, Bucaramanga, Colombia

  collaborator UNKNOWN

• Hospital Universitario Erasmo Meoz, Cucuta, Colombia

  collaborator UNKNOWN

• Fundación Valle del Lili, Cali, Colombia

  collaborator UNKNOWN

• Hospital Regional de Loreto, Iquitos, Peru

  collaborator UNKNOWN

• Instituto de Infectologia Emílio Ribas, São Paulo, Brazil

  collaborator UNKNOWN

• Universitas Sumatera Utara, Medan, Indonesia

  collaborator UNKNOWN

• Airlangga University (UNAIR), Indonesia

  collaborator UNKNOWN

• University Malaya Medical Centre, Malaysia

  collaborator UNKNOWN

• Hospital Queen Elizabeth II, Malaysia

  collaborator UNKNOWN

• San Lazaro Hospital (SLH-NU), Manila, Philippines

  collaborator UNKNOWN

• Oxford University Clinical Research Unit, Vietnam

  lead OTHER

Principal Investigators

• Sophie Yacoub, MD., PhD. · University of Oxford, UK

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Model

FACTORIAL

Eligibility

Min Age

5 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2026-10-01

Primary Completion

2030-07-31

Completion

2031-07-31

Countries

• Bangladesh
• Brazil
• Colombia
• Indonesia
• Malaysia
• Nepal
• Peru
• Philippines
• Thailand
• Vietnam

Study Locations