DenguePhase 2/3NCT07016321
Emetine for Viral Outbreaks (a.k.a. EVOLVE Antiviral Initiative)
A Phase 2/3 study testing Emetine Hydrochloride 6mg and Emetine Hydrochloride 12mg in people with Dengue, run by Johns Hopkins University at 2 sites in 2 countries.
Trial summary
The goal of this study is to evaluate the efficacy and safety of emetine administered orally for symptomatic patients aged 18-65 years infected with the dengue virus. The main questions it aims to answer are: 1. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Dengue
- What is being tested?
- Emetine Hydrochloride 6mg and Emetine Hydrochloride 12mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 600 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 1 Sep 2026to 3 May 2029
- Phase
- Phase 2/3
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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18 to 65 years
- Admitted to the hospital
- Laboratory-confirmed infection with dengue virus within the last 5 days and preferably within the last 3 days. Testing for dengue virus using positive Nonstructural protein 1(NS1) strip assay or reverse-transcriptase polymerase chain reaction (RT-PCR)
- Having two or more clinical symptoms (fever, headache, retro-orbital pain, myalgia, arthralgia, rash, hemorrhagic manifestations, or leucopenia, gastrointestinal symptoms) with the onset of fever within 72 hours of presentation, and
- Able to provide voluntary informed consent and comply with all study procedures and visits.
Who cannot join
- Age ≥65 years
- Pregnant or breastfeeding
- Current or recent use of the study drug
- Known allergy to study drug
- Current or planned participation in another pharmacological interventional trial in the next 10 days
- Participants with known past history of dengue infection
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- Participants on aspirin, anticoagulants, or with other conditions that might increase the risk of bleeding
- Participants on immunosuppressive agents, including long-term steroids
- Severe dengue as defined by the WHO 2009 revised case classification.
- Individuals with long-term immunosuppressive agents such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or those on systemic corticosteroid therapy
- History of prior vaccination against dengue fever within one year.
- Patients who have recently used ayurvedic or herbal medications for dengue or any other conditions in the last 7 days (eg, Papaya leaf extract)
Trial locations and contacts
2 sites in 2 countries. Contact the study team or a site near you to ask about taking part.
2 sites in 2 countries
United States1 site, 1 recruiting
- Not yet recruiting
Johns Hopkins University, Division of Infectious Disease
Baltimore, Maryland, 21231
Kunchok Dorjee, MBBS, PhD, 410-502-7135, kdorjee1@jhmi.edu
Kunchok Dorjee, MBBS, PhD
Nepal1 site, 1 recruiting
- Recruiting
Bharatpur Hospital
Bharatpur-10, Chitwan
Kalyan Sapkota, MD, +977-9851143296, kalyansapkota@gmail.com
Kalyan Sapkota, MD
About this study
Official title: Emetine for Viral Outbreaks: A Phase 2/3 Randomized, Double-Blinded, Placebo-Controlled Trial to Evaluate the Efficacy and Safety of Emetine for Dengue Fever (a.k.a. EVOLVE Antiviral Initiative)
The goal of this study is to evaluate the efficacy and safety of emetine administered orally for symptomatic patients aged 18-65 years infected with the dengue virus. The main questions it aims to answer are:
- Does emetine reduce 28-day mortality or progression to severe dengue (severe plasma leakage, severe bleeding, or severe organ involvement)?
- What are the safety outcomes of emetine, including serious adverse events and toxicities?
Read more
Participants will be asked to:
- Take either 6mg emetine, 12mg emetine, or a placebo pill for 7 consecutive days as part of the treatment regimen.
- Have blood samples taken for at least 5 days to monitor viral load, inflammatory markers, and safety parameters.
- Be monitored by healthcare staff for daily vital signs and symptoms for clinical assessments for 28 days.
Read the detailed description
Dengue fever is a mosquito-borne viral infection caused by the dengue virus (DENV), which belongs to the Flaviviridae family. It is transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes. Dengue is recognized as one of the top ten global public health threats, affecting an estimated 390 million people annually, with approximately 96 million cases manifesting clinically. Globally, dengue has seen a significant rise in incidence, with a 30-fold increase in the past 50 years. There is currently no antiviral agent proven to work against it. Dengue fever is endemic in Nepal with cyclical outbreaks. The country relies on supportive treatment. This often includes intravenous fluids and, in rare cases, steroids and organ support. Effective antiviral agents could significantly reduce the burden of dengue by preventing disease progression and reducing transmission.
In vitro and in vivo studies have suggested strong antiviral activity of emetine against SARS-CoV-2, dengue, Ebola, cytomegalovirus, and several other viruses. Low et al. had carefully demonstrated that emetine inhibited all four serotypes of DENV infection in cell lines by inhibiting the viral RNA synthesis or the viral protein translation pathway. In the past, emetine, an alkaloid extracted from ipecacuanha roots, has been widely used in the human treatment of amoebic dysentery, amoebic liver abscess, and several viruses such as herpes simplex, herpes zoster, influenza, hepatitis, and mumps. Because of cardiotoxicity (cardiac dysrhythmias), emetine was replaced by metronidazole. The toxicity was unequivocally associated with high-dose emetine (60 mg/day for 10 days to achieve an minimum inhibitory concentration (MIC) of 25 micromol (µM) against Entamoeba histolytica; however, the cardiovascular side-effects were minimal or none when emetine was used for various indications in low dose (<20 mg/day). The investigators have recently shown that by lowering the standard amoebicidal dose by a factor of 10, emetine can inhibit viral replication while avoiding cardiovascular toxicity.
Phase 1 and 2 studies have been previously carried out. The investigators' clinical trial to evaluate emetine against SARS-CoV-2 is currently approved by Johns Hopkins Medicine (JHM) Institutional Review Board (IRB) (IRB00283778) and is ongoing in Nepal. The investigators have enrolled a few patients in this trial and have not encountered any toxicity. Given the broad-spectrum antiviral activity of emetine, the investigators now plan to evaluate emetine's efficacy and safety in the treatment of symptomatic dengue fever in a clinical trial. The investigators hypothesize that emetine will be efficacious against dengue at low doses. By evaluating its efficacy against dengue, this research can directly inform treatment strategies for patients in over 100 countries, since about 50% of the global population is at risk of dengue fever. In the past, emetine was an essential World Health Organization (WHO)- and FDA-approved drug.
- Conditions
- Dengue
- Being tested
- Emetine Hydrochloride 6mg, Placebo, Emetine Hydrochloride 12mg
- Medical subject headings
- Dengue
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Emetine Hydrochloride 6mgDrug
To administer Emetine Hydrochloride 6mg orally for 10 consecutive days to evaluate the efficacy and safety of emetine for symptomatic dengue patients.
PlaceboDrug
Participant take a placebo for 10 consecutive days.
Emetine Hydrochloride 12mgDrug
To administer Emetine Hydrochloride 12mg orally for 10 consecutive days to evaluate the efficacy and safety of emetine for symptomatic dengue patients.
| Study group | Role | What they receive |
|---|---|---|
| Emetine 6 mg | Active comparator | Participants take 6mg Emetine pill for 10 consecutive days Receives: Drug: Emetine Hydrochloride 6mg |
| Emetine 12 mg | Active comparator | Participants take 12mg Emetine pill for 10 consecutive days Receives: Drug: Emetine Hydrochloride 12mg |
| Placebo | Placebo comparator | Participant take a placebo for 10 consecutive days Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate effectiveness of emetine in dengue patients assessed by 28-day mortality or progression
28-day mortality or progression to severe dengue, defined as severe plasma leakage, severe bleeding, or severe organ involvement (death and severe dengue will be assessed as a composite outcome)
Measured: 28 days
Safety of emetine assessed by number of adverse events
Record serious adverse events and toxicities by organ-system
Measured: Up to 28 days
Safety of emetine assessed by rate of drug discontinuation
Evaluate the safety of emetine assessed by rate of drug discontinuation
Measured: Up to 28 days
Secondary outcomes (12)
Recovery (≥ 3 days without symptoms)
Sustained resolution of all dengue symptoms for ≥ 3 consecutive days (where the first of those days is considered the date of recovery)
Measured: Up to 14 days
Time to Virologic Clearance of Dengue Virus by Qualitative RT-PCR
Time to test negativity that is longitudinally measured by Qualitative real-time polymerase chain reaction (RT-PCR).
Measured: Pre-dose (day 0), day 3, and day 5
Quantitative Viral Load Assessment by RT-PCR Cycle Threshold (Ct) Values
Measures of the average RT-PCR cycle threshold (Ct) values for dengue virus RNA at specified time points post-randomization.
Measured: Days 0,3, 5
Changes in inflammatory marker measured by hematocrit
Measure hematocrit in percentage (%) for patients
Measured: Days 0 to 5
Changes in inflammatory marker measured by white blood count
Measure white blood count (WBC) for patients measured per microliter (mcL)
Measured: Day 0-5
Changes in inflammatory marker measured by reticulocyte count
Measure reticulocyte count as percentage (%) for patients
Measured: Day 0-5
Changes in inflammatory marker measured by platelet count
Measure platelet count for patients measured per microliter (mcL)
Measured: Day 0-5
Changes in inflammatory marker measured by alanine aminotransferase
Measure alanine aminotransferase (ALT) for patients in units per liter (U/L)
Measured: Day 0-5
Changes in inflammatory marker measured by serum bilirubin
Measure serum bilirubin for patients in milligrams per deciliter (mg/dL)
Measured: Day 0-5
Changes in inflammatory marker measured by serum albumin
Measure serum albumin for patients in grams per deciliter (g/dL)
Measured: Day 0-5
Changes in inflammatory marker measured by C-reactive protein
Measure C-reactive protein (CRP) for patients in milligrams per liter (mg/L)
Measured: Day 0-5
Post infection fatigue measured by Fatigue Questionnaire
Fatigue will be measured using the validated 11-item Fatigue Questionnaire (FQ), which assesses both physical (7 items) and mental (4 items) fatigue. Each item is rated on a 4-point Likert scale (0 = none, 3 = severe), with total scores ranging from 0 to 33, where higher scores indicate greater fatigue severity.
Measured: On Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2025
- Study start1 Sep 2026
- Primary completion1 Mar 2029 (estimated)
- Study completion3 May 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (8)Papers the sponsor has linked to this study.
- Other trials for DengueStudies of the same condition, open and under way.
- More trials run by Johns Hopkins UniversityThe sponsor's other registered studies.
- 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomly assigned to one of three arms: intervention arm #1 (6 mg emetine), intervention arm #2 (12 mg emetine), or the control arm (matching oral placebo) based on a pre-designed scheme of block randomization.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Johns Hopkins University
- Sponsor type
- University, hospital or other
- Collaborators
- Bharatpur Hospital Chitwan
- Responsible party
- Sponsor
- Investigators
- Kunchok Dorjee, MBBS, PhD, Principal investigator, Johns Hopkins University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07016321
- Sponsor's protocol ID
- IRB00486563
- Status last verified
- Oct 2026
- First submitted
- 20 May 2025
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Choy KT, Wong AY, Kaewpreedee P, Sia SF, Chen D, Hui KPY, Chu DKW, Chan MCW, Cheung PP, Huang X, Peiris M, Yen HL. Remdesivir, lopinavir, emetine, and homoharringtonine inhibit SARS-CoV-2 replication in vitro. Antiviral Res. 2020 Jun;178:104786. doi: 10.1016/j.antiviral.2020.104786. Epub 2020 Apr 3.
PubMed 32251767Ooi EE. Repurposing Ivermectin as an Anti-dengue Drug. Clin Infect Dis. 2021 May 18;72(10):e594-e595. doi: 10.1093/cid/ciaa1341. No abstract available.
PubMed 33124646Bhat CS, Shetty R, Sundaram B, Ramanan AV. Immunomodulatory therapy in dengue: need for clinical trials and evidence base. Arch Dis Child. 2023 Jun;108(6):451-452. doi: 10.1136/archdischild-2022-324100. Epub 2022 Jun 9. No abstract available.
PubMed 35680407Guzman MG, Gubler DJ, Izquierdo A, Martinez E, Halstead SB. Dengue infection. Nat Rev Dis Primers. 2016 Aug 18;2:16055. doi: 10.1038/nrdp.2016.55.
PubMed 27534439Beesetti H, Khanna N, Swaminathan S. Investigational drugs in early development for treating dengue infection. Expert Opin Investig Drugs. 2016 Sep;25(9):1059-69. doi: 10.1080/13543784.2016.1201063. Epub 2016 Jun 24.
PubMed 27322111Entner N, Grollman AP. Inhibition of protein synthesis: a mechanism of amebicide action of emetine and other structurally related compounds. J Protozool. 1973 Feb;20(1):160-3. doi: 10.1111/j.1550-7408.1973.tb06025.x. No abstract available.
PubMed 4347870Bleasel MD, Peterson GM. Emetine Is Not Ipecac: Considerations for Its Use as Treatment for SARS-CoV2. Pharmaceuticals (Basel). 2020 Nov 27;13(12):428. doi: 10.3390/ph13120428.
PubMed 33261173Grollman AP. Structural basis for inhibition of protein synthesis by emetine and cycloheximide based on an analogy between ipecac alkaloids and glutarimide antibiotics. Proc Natl Acad Sci U S A. 1966 Dec;56(6):1867-74. doi: 10.1073/pnas.56.6.1867. No abstract available.
PubMed 16591432