Dengue Fever
Conditions
Keywords
Resomelagon, Resolution of inflammation, Melanocortin, Dengue, RESOVIR-2
Brief summary
The goal of this clinical trial is to understand if Resomelagon can treat adult patients with Dengue virus infection. The main questions the investigators aim to answer are: Is Resomelagon safe to use in patients with Dengue? Is Resomelagon able to reduce the duration of illness? (defined by clinical and laboratory criteria) Participants will be allocated to Resomelagon or placebo groups in this study and asked to take the medication and submitted to blood tests.
Detailed description
Complications of dengue infection follows the peak of viremia and are associated with increased activation of the immune response. Proof-of-concept studies in animal models of dengue infection have shown that blocking certain aspects of the inflammatory response or the administration of pro-resolving molecules is beneficial in experimental dengue. In these experiments, the administration of certain anti-inflammatory or pro-resolution molecules decreases disease severity and aspects of the inflammatory response, including changes in vascular permeability. We have previously shown that treatment with RESOMELAGON decreased lung inflammation and outcome in animal models of beta coronavirus infection (including by SARS-CoV-2) and decreased disease severity in COVID-19 patients, even in the presence of glucocorticoid therapy. Preclinical experiments also showed that RESOMELAGON decreased disease severity in an animal model of dengue infection and decreased cytokine release by human PBMC infected with dengue virus. RESOMELAGON is safe in healthy individuals, those with rheumatoid arthritis, and patients with COVID-19. This is a placebo controlled, randomized, double-blinded clinical trial evaluating the safety and efficacy of Resomelagon in patients with acute dengue infection.
Interventions
DRUGResomelagon
Resomelagon 100mg, orally, once daily.
DRUGPlacebo
Placebo
OTHERStandard Treatment
Hydration and symptomatic therapy as indicated for Dengue fever.
Sponsors
Federal University of Minas Gerais
Instituto Nacional de Ciência e Tecnologia em Dengue (INCT em Dengue)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patients who are 18 to 65 years old; * Able to understand study procedures and give informed consent; * Presents with more than 36 and less than 84h since symptoms onset; * Symptoms compatible with dengue infection (fever, myalgia, arthralgia, headache or conjunctivitis) with positive antigen test or polymerase chain reaction test.
Exclusion criteria
* Has any comorbidity which is perceived as significant by the investigator; * Significant laboratory abnormalities discovered at triage: Hemoglobin \<10g/dL; Platelet count \< 50.000/microL; alanine transaminase \> 3x upper limit of normal; Total bilirubin \>1,5 x upper limit of normal; glomerular filtration rate \< 60mls/min/1,73m2; * Contraindications or known hypersensitivity to Resomelagon; * Presents as dengue with warning signs or severe dengue at inclusion; * Currently participating in another drug clinical trial; * Clinical evidence of another infection that might explain current symptoms; * Pregnant women or women actively trying to achieve pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluate safety of Resomelagon in Dengue patients | 28 days | Incidence of clinical or laboratory adverse events. All symptoms, illness and laboratory abnormalities will be graded by the investigators in accordance to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Adverse events graded 3 or more in severity will be registered. Serious adverse events will be reported and registered. Incidence of adverse events will be compared between placebo and intervention groups. |
| Efficacy of Resomelagon in decreasing illness duration | 10 days | Time to resolution of illness as defined by a composite outcome: Patient afebrile for 48 hours without paracetamol (or other drugs to treat fever) ingestion; Rising platelet counts of \>20% of the lowest, or normal platelet counts if the patient did not have thrombocytopenia, following two consecutive measurements from the lowest platelet count Haematocrit stabilized or return to the normal hematocrit for age \& sex, following two consecutive measurements Absence of bleeding or significant vomiting for 48h. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Resomelagon in reducing illness Severity | 10 days | Incidence of dengue with warning signs or severe dengue in the study patients |
| Efficacy of Resomelagon in reducing plasma leakage | 10 days | Incidence of hemoconcentration (hematocrit increase of \>10% from inclusion or elevated for age \& sex) OR evidence of pleural effusion OR evidence of ascitis OR pericardial effusion |
| Efficacy of Resomelagon in reducing dengue hospitalization or prolonged observation in the Emergency department | 10 days | Incidence of a stay of more than 12h in the emergency department or hospital admission |
Countries
Brazil
Contacts
CONTACTPedro RJ Almeida, MD MSc
PRINCIPAL_INVESTIGATORMauro M Teixeira, MD PhD
Federal University of Minas Gerais
Outcome results
None listed