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Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE) (ZAP-DENGUE)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04597437
Recruitment Status : Not yet recruiting
First Posted : October 22, 2020
Last Update Posted : October 22, 2020
Sponsor:
Collaborators:
Naval Medical Research Center
Hospital Infantil de Niño Jesús de Barranquilla (HINJ)
Universidad Bosque
Allied Research Society
Information provided by (Responsible Party):
George Washington University

Brief Summary:
ZAP-DENGUE is a pilot randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of five days of intravenous zanamivir treatment to treat vascular permeability syndrome which is the main cause of death in dengue fever.

Condition or disease Intervention/treatment Phase
Dengue Fever Drug: Zanamivir Other: Placebo Early Phase 1

Detailed Description:

ZAP-DENGUE is a pilot randomized, double-blind, placebo-controlled evaluation of the safety and efficacy of five days of intravenous zanamivir treatment to treat vascular permeability syndrome which is the main cause of death in dengue fever. Our central hypothesis is that zanamivir treatment is safe in patients with dengue infection, will significantly decrease serum sialic acid levels, and will result in fewer patients with the development of moderate or severe clinical plasma leakage. 74 male and non-pregnant female volunteers age 7 years and older from Colombia with a diagnosis of dengue fever with warning signs or severe dengue as per the World Health Organization 2009 definition with the presence of fever and positive rapid test for the presence of dengue non-structural protein-1 (NS1) will be randomized to zanamivir versus placebo. In the treatment group, participants will receive 600 mg for adults and 12 mg/kg in children intravenously every twelve hours for 5 days adjusted for renal function. In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.

All patients will receive blood draws for assessment of hematocrit, renal function, and biologic efficacy endpoints and clinical evaluation of signs and symptoms of vascular permeability (which may include ultrasound and radiograph) and adverse events daily during the five days of medication administration and once at follow up at 14 days.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 74 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Pilot, randomized, double-blind, placebo-controlled trial of the safety and efficacy of inhaled zanamivir (n=37) versus placebo (n=37) therapy for dengue
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE): A Pilot Randomized Controlled Trial
Estimated Study Start Date : October 1, 2021
Estimated Primary Completion Date : September 30, 2022
Estimated Study Completion Date : September 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Dengue Fever
Drug Information available for: Zanamivir

Arm Intervention/treatment
Experimental: Zanamivir
In the treatment group, participants will receive 600 mg for adults and 12 mg/kg in children intravenously every twelve hours for 5 days adjusted for renal function.
Drug: Zanamivir
Intravenous zanamivir

Placebo Comparator: Placebo
In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.
Other: Placebo
In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.




Primary Outcome Measures :
  1. Incidence of Treatment-Emergent Adverse Events of intravenous zanamivir treatment versus placebo in dengue [ Time Frame: Over 14 days ]
    Incidence of Treatment-Emergent Adverse Events will be assessed by daily active surveillance during drug administration and at 2-week follow-up as per the United States Food and Drug Administration guidelines.


Secondary Outcome Measures :
  1. Levels of endothelial glycocalyx biomarkers in intravenous zanamivir treatment versus placebo in dengue [ Time Frame: Over 14 days ]

    Serum concentration of key endothelial glycocalyx components due to endothelial damage such as sialic acid, heparan sulfate, and syndecan-1 will be assessed by ELISA.

    Serum concentration of sialidases (NEU2 and NEU3) that are directly inhibited by zanamivir will be assessed by ELISA.


  2. Preliminary clinical efficacy of intravenous zanamivir treatment versus placebo in dengue [ Time Frame: Over 14 days ]
    Presence of moderate or severe plasma leakage as defined by the Standard Clinical Endpoints for Use in Dengue Interventional Trials where moderate plasma leakage is defined as 15% change in hematocrit or evidence of fluid on ultrasound or X-ray and severe plasma leakage is defined at the presence of shock or respiratory compromise with evidence of plasma leakage.



Information from the National Library of Medicine

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Ages Eligible for Study:   7 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Provision of signed and dated informed consent form.
  2. Stated willingness to comply with all study procedures and availability for the duration of the study.
  3. Male or female, aged >7 years
  4. Willingness to receive intravenous medication and be willing to adhere to the medication regimen
  5. Have a diagnosis of dengue by dengue NS1 rapid test
  6. Have had a documented fever >38C in the last 24 hours.
  7. Have dengue with warning signs as per the 2009 WHO criteria including one of the following: abdominal pain or tenderness, persistent vomiting, clinical fluid accumulation, mucosal bleeding, lethargy, restlessness, liver enlargement over 2 cm, augmented hematocrit, thrombocytopenia or severe dengue defined as dengue with severe plasma leakage leading to dengue shock and/or fluid accumulation with respiratory distress; severe hemorrhage; severe organ impairment (hepatic damage, renal impairment, cardiomyopathy, encephalopathy or encephalitis).

Exclusion Criteria:

  1. Pregnancy or lactation
  2. Children in Care of the state
  3. Patients who are unlikely to survive 48 hours
  4. Elevated alanine aminotransferase ≥3 times the upper limit of normal (ULN)
  5. Total bilirubin ≥2 × ULN
  6. Unstable cardiac disease or arrhythmia at baseline
  7. History of significant cardiac disease
  8. Treatment with another investigational drug or other intervention within 1 month.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04597437


Contacts
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Contact: Aileen Y Chang, MD 202-741-6562 chang@email.gwu.edu

Sponsors and Collaborators
George Washington University
Naval Medical Research Center
Hospital Infantil de Niño Jesús de Barranquilla (HINJ)
Universidad Bosque
Allied Research Society
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Responsible Party: George Washington University
ClinicalTrials.gov Identifier: NCT04597437    
Other Study ID Numbers: NCR203024
First Posted: October 22, 2020    Key Record Dates
Last Update Posted: October 22, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: De-identified information can be shared with other investigators. Please contact Dr. Aileen Chang at chang@email.gwu.edu

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No
Additional relevant MeSH terms:
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Dengue
Arbovirus Infections
Virus Diseases
Flavivirus Infections
Flaviviridae Infections
RNA Virus Infections
Hemorrhagic Fevers, Viral
Zanamivir
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action