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

• ClinicalTrials.gov Identifier: NCT04597437
• Recruitment Status: Not yet recruiting
• First Posted: October 22, 2020
• Last Update Posted: October 22, 2020
• Sponsor: George Washington University
• 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

Tracking Information

• First Submitted Date: October 9, 2020
• First Posted Date: October 22, 2020
• Last Update Posted Date: October 22, 2020
• Estimated Study Start Date: October 1, 2021
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 15, 2020)

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.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted

Current Secondary Outcome Measures (submitted: October 15, 2020)

• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE)
• Official Title: Zanamivir Treatment of Vascular Permeability in Dengue (ZAP-DENGUE): A Pilot Randomized Controlled Trial
• 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, 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.

• Study Type: Interventional
• Study Phase: Early Phase 1

Study Design

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

• Condition: Dengue Fever

Intervention

• Drug: Zanamivir
  Intravenous zanamivir
• Other: Placebo
  In the placebo group, participants will receive placebo normal saline solution intravenously every twelve hours for 5 days.

Study Arms

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

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Not yet recruiting
• Estimated Enrollment (submitted: October 15, 2020): 74
• Original Estimated Enrollment: Same as current
• Estimated Study Completion Date: September 30, 2022
• Estimated Primary Completion Date: September 30, 2022 (Final data collection date for primary outcome measure)

Eligibility 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 7 Years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

Contacts

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

• Listed Location Countries: Not Provided

Administrative Information

• NCT Number: NCT04597437
• Other Study ID Numbers: NCR203024
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

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

• Responsible Party: George Washington University
• Study Sponsor: George Washington University

Collaborators

• Naval Medical Research Center
• Hospital Infantil de Niño Jesús de Barranquilla (HINJ)
• Universidad Bosque
• Allied Research Society

• Investigators: Not Provided
• PRS Account: George Washington University
• Verification Date: October 2020