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

Primary Purpose

Dengue Fever

Status
Not yet recruiting
Phase
Early Phase 1
Locations
Study Type
Interventional
Intervention
Zanamivir
Placebo
Sponsored by
George Washington University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dengue Fever

Eligibility Criteria

7 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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).
  8. Enrollment in EPS (Entidadas Promotoras de Salud) or Sistema General de Seguridad Social en Salud (SGSSS)- Colombian Public Health Insurance.

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.
  9. Encephalitis or unable to consent

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Placebo Comparator

    Arm Label

    Zanamivir

    Placebo

    Arm Description

    In the treatment group, participants weighing less than 50 kg will receive 12 mg/kg and those weighing 50 kg and above will receive 600 mg as the initial dose 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.

    Outcomes

    Primary Outcome Measures

    Incidence of Treatment-Emergent Adverse Events of intravenous zanamivir treatment versus placebo in dengue
    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

    Levels of endothelial glycocalyx biomarkers in intravenous zanamivir treatment versus placebo in dengue
    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.
    Preliminary clinical efficacy of intravenous zanamivir treatment versus placebo in dengue
    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.

    Full Information

    First Posted
    October 9, 2020
    Last Updated
    September 1, 2023
    Sponsor
    George Washington University
    Collaborators
    Naval Medical Research Center, Clinica de la Costa, Global Disease Research
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    1. Study Identification

    Unique Protocol Identification Number
    NCT04597437
    Brief Title
    Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE)
    Acronym
    ZAP-DENGUE
    Official Title
    Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE): A Pilot Randomized Controlled Trial
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    September 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    December 1, 2023 (Anticipated)
    Primary Completion Date
    June 30, 2024 (Anticipated)
    Study Completion Date
    June 30, 2024 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    George Washington University
    Collaborators
    Naval Medical Research Center, Clinica de la Costa, Global Disease Research

    4. Oversight

    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
    Data Monitoring Committee
    Yes

    5. Study Description

    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.
    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, all participants weighing less than 50 kg will receive 12 mg/kg and all participants weighing 50 kg and above will receive 600 mg as the initial dose 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Dengue Fever

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Early Phase 1
    Interventional Study Model
    Parallel Assignment
    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
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    74 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Zanamivir
    Arm Type
    Experimental
    Arm Description
    In the treatment group, participants weighing less than 50 kg will receive 12 mg/kg and those weighing 50 kg and above will receive 600 mg as the initial dose intravenously every twelve hours for 5 days adjusted for renal function.
    Arm Title
    Placebo
    Arm Type
    Placebo Comparator
    Arm Description
    In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.
    Intervention Type
    Drug
    Intervention Name(s)
    Zanamivir
    Intervention Description
    Intravenous zanamivir
    Intervention Type
    Other
    Intervention Name(s)
    Placebo
    Intervention Description
    In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.
    Primary Outcome Measure Information:
    Title
    Incidence of Treatment-Emergent Adverse Events of intravenous zanamivir treatment versus placebo in dengue
    Description
    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.
    Time Frame
    Over 14 days
    Secondary Outcome Measure Information:
    Title
    Levels of endothelial glycocalyx biomarkers in intravenous zanamivir treatment versus placebo in dengue
    Description
    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.
    Time Frame
    Over 14 days
    Title
    Preliminary clinical efficacy of intravenous zanamivir treatment versus placebo in dengue
    Description
    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.
    Time Frame
    Over 14 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    7 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Provision of signed and dated informed consent form. Stated willingness to comply with all study procedures and availability for the duration of the study. Male or female, aged >7 years Willingness to receive intravenous medication and be willing to adhere to the medication regimen Have a diagnosis of dengue by dengue NS1 rapid test Have had a documented fever >38C in the last 24 hours. 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). Enrollment in EPS (Entidadas Promotoras de Salud) or Sistema General de Seguridad Social en Salud (SGSSS)- Colombian Public Health Insurance. Exclusion Criteria: Pregnancy or lactation Children in Care of the state Patients who are unlikely to survive 48 hours Elevated alanine aminotransferase ≥3 times the upper limit of normal (ULN) Total bilirubin ≥2 × ULN Unstable cardiac disease or arrhythmia at baseline History of significant cardiac disease Treatment with another investigational drug or other intervention within 1 month. Encephalitis or unable to consent
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Aileen Y Chang, MD
    Phone
    202-741-6562
    Email
    chang@email.gwu.edu

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    De-identified information can be shared with other investigators. Please contact Dr. Aileen Chang at chang@email.gwu.edu

    Learn more about this trial

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

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