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Anakinra in Dengue With Hyperinflammation ( AnaDen )

Primary Purpose

Dengue, Dengue With Warning Signs, Severe Dengue

Status
Not yet recruiting
Phase
Phase 2
Locations
Vietnam
Study Type
Interventional
Intervention
Placebo
Anakinra
Sponsored by
Oxford University Clinical Research Unit, Vietnam
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Dengue focused on measuring Dengue, Hyperinflammatory syndrome, Anakinra, Vietnam

Eligibility Criteria

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

Inclusion Criteria: Patients hospitalised with a clinical diagnosis of dengue and at least 1 warning sign(s) (see appendix) or severe dengue to Emergency department/inpatient wards/Intensive Care wards (ICU), Ferritin levels > 2000ng/mL ≥ 12 years of age Written informed consent or assent to participate in the study Agree to come back for 2 follow up visits around day 30 of illness (maximum 5 weeks) and at 3 months Exclusion Criteria: Pregnancy Localizing features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis Patients taking immunosuppressive drugs or other biologics in last 1 month Patients with underlying malignancy or immunosuppression Children <12 years Have end-stage renal failure (baseline GFR < 30ml/min) Being treated for TB Taking any drug with significant interaction with anakinra The study physician judges that the patient is unlikely to attend follow up visit at around 3-4 weeks after fever onset - e.g. due to long travelling distance from the clinic

Sites / Locations

  • Hospital for Tropical Diseases

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Anakinra

Arm Description

The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.

The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.

Outcomes

Primary Outcome Measures

Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)

Secondary Outcome Measures

Mortality
Number of death up to day 30
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7
Change in mSOFA score at day 7 post randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
Number of days treated in Intensive care unit (ICU)
Number of days treated in ICU
Number of days treated in hospital
Number of days treated in hospital
Number of participants with Serious Adverse Events (SAEs)
Number of participants having SAEs within 2 time-periods, 1- 5 days and 6-30 days
Number of Adverse Events (AEs) per participant
Number of AEs per individual
Change in Platelets count
Change in blood levels (Platelets) over 5 days following randomization and at day 30
Change in neutrophils count
Change in blood levels (neutrophils) over 5 days following randomization and at day 30
Change of ALT levels
Change in blood levels (ALT) over 5 days following randomization and at day 30
Change of Ferritin levels
Change in blood levels (Ferritin) over 5 days following randomization and at day 30
Change of CRP levels
Change in blood levels (CRP) over 5 days following randomization and at day 30
Time to normalization of blood levels
Time to normalization of platelets (defined as >150 x109/l) and neutrophils (>2 x109/l)
Platelet nadir
Lowest platelet count recorded during admission
Fever clearance time
Time to temperature <37.5 for at least 48 hours
Duration of viraemia
Number of days from enrollment to the first undetectable viraemia (negative in qPCR and NS1)
Area under the curve (AUC) of the serial viral load measurements during hospital stay
AUC of viral load measurements during hospital stay will be reported
Patients' quality of life questionnaire score
Patients' quality of life during their hospitalisation will be explored at discharge and day 30 using the EQ-5D questionnaire.

Full Information

First Posted
October 19, 2022
Last Updated
August 30, 2023
Sponsor
Oxford University Clinical Research Unit, Vietnam
Collaborators
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
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1. Study Identification

Unique Protocol Identification Number
NCT05611710
Brief Title
Anakinra in Dengue With Hyperinflammation ( AnaDen )
Official Title
Anakinra for Dengue Patients With Hyperinflammation - a Randomized Double-blind Placebo-controlled Trial
Study Type
Interventional

2. Study Status

Record Verification Date
August 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
September 30, 2023 (Anticipated)
Primary Completion Date
December 31, 2025 (Anticipated)
Study Completion Date
December 31, 2027 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Oxford University Clinical Research Unit, Vietnam
Collaborators
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This study aims to evaluate the effect of anakinra in dengue patients with hyperinflammation as compared to placebo Primary Objective: To evaluate the efficacy of Anakinra in moderate-severe dengue patients with hyperinflammation. Secondary Objectives: To assess the safety of anakinra therapy in dengue with hyperinflammation To assess the effect of anakinra therapy in patients with dengue on physiological, clinical and virological parameters To assess the immunomodulation effects of anakinra in dengue Immune cell signatures in dengue with and without anakinra To assess difference in gene expression between treatment group compared to non-treatment population
Detailed Description
This is a randomized double blinded placebo controlled trial investigating the effects of four days of anakinra treatment on dengue patients with hyperinflammatory syndrome. The anakinra/placebo will be given to eligible participants admitted to the Hospital for Tropical Diseases (HTD) in Ho Chi Minh City, Vietnam. 160 dengue patients will be randomly assigned to either anakinra or placebo intervention group to receive treatment for 4 days. Patients admitted to the HTD with a clinical diagnosis of dengue and at least 1 warning sign(s) or severe dengue to Emergency department / inpatient wards / Intensive Care Units (ICU), will be invited to participate in the trial. Eligible patients will be invited to participate in the screening phase during which, the collection of clinical information about this acute illness episode as well as some screening tests will be performed, including measurement ferritin, creatinine, pregnancy test (for all females). - If ferritin level is greater than 2000ng/mL and meet all other inclusion/exclusion criteria, patients will be invited to participate in the randomization phase (second consent), which they will be randomly given either anakinra or placebo intravenous (IV) for four days. The intervention: (i) 200mg bid for four days in adults participants (≥ 16 years) or in children (12-16 years), with weight > 50kg; and (ii) 2mg/kg bid for four days in children (12-16 years), with weight < 50Kg. All patients will be followed up daily at the clinical wards until discharge. Details of all AEs and SAEs will be recorded on specific forms, together with an assessment as to whether the events are likely to have been related to any treatment received. All SAEs will be reported promptly to the DMC and ECs according to policy. In cases of discontinuation due to AEs, participants will be followed up until the events have resolved or stabilized.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Dengue, Dengue With Warning Signs, Severe Dengue, Anakinra, Immuno-modulation, Anti-inflammatory Agents, Macrophage Activation Syndrome, Hyperinflammatory Syndrome, Cytokine Storm
Keywords
Dengue, Hyperinflammatory syndrome, Anakinra, Vietnam

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
This is a randomized, double blinded, placebo controlled trial of anakinra in patients with dengue with warning signs or severe dengue
Masking
ParticipantInvestigator
Masking Description
Double blinded
Allocation
Randomized
Enrollment
160 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.
Arm Title
Anakinra
Arm Type
Experimental
Arm Description
The intervention group will include 80 dengue patients with warning signs or severe dengue receiving anakinra.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Drug: Placebo, with visually matched clear syringes Adults (≥16 years) and children (12-16 years, > 50Kg) will receive 2 syringes of placebo via IV route, twice daily for 4 days Children (12-16 years, < 50Kg) will receive no more than 1 syringe of placebo via IV route, twice daily for 4 days
Intervention Type
Drug
Intervention Name(s)
Anakinra
Intervention Description
Drug: Anakinra Adults (≥16 years) and children (12-16 years, > 50Kg) will receive 200mg of anakinra (2 syringes) via IV route, twice daily for 4 days Children (12-16 years, < 50Kg) will receive 2mg/Kg of anakinra via IV route, twice daily for 4 days (no more than 1 syringe of anakinra, twice daily for 4 days)
Primary Outcome Measure Information:
Title
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
Description
Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
Time Frame
baseline, up to day 4
Secondary Outcome Measure Information:
Title
Mortality
Description
Number of death up to day 30
Time Frame
Up to day 30
Title
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7
Description
Change in mSOFA score at day 7 post randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
Time Frame
baseline, day 7
Title
Number of days treated in Intensive care unit (ICU)
Description
Number of days treated in ICU
Time Frame
Up to day 30
Title
Number of days treated in hospital
Description
Number of days treated in hospital
Time Frame
Up to day 30
Title
Number of participants with Serious Adverse Events (SAEs)
Description
Number of participants having SAEs within 2 time-periods, 1- 5 days and 6-30 days
Time Frame
Day 1-5 and Day 6-30
Title
Number of Adverse Events (AEs) per participant
Description
Number of AEs per individual
Time Frame
Up to day 30
Title
Change in Platelets count
Description
Change in blood levels (Platelets) over 5 days following randomization and at day 30
Time Frame
Up to day 5, at day 30
Title
Change in neutrophils count
Description
Change in blood levels (neutrophils) over 5 days following randomization and at day 30
Time Frame
Up to day 5, at day 30
Title
Change of ALT levels
Description
Change in blood levels (ALT) over 5 days following randomization and at day 30
Time Frame
Up to day 5, at day 30
Title
Change of Ferritin levels
Description
Change in blood levels (Ferritin) over 5 days following randomization and at day 30
Time Frame
Up to day 5, at day 30
Title
Change of CRP levels
Description
Change in blood levels (CRP) over 5 days following randomization and at day 30
Time Frame
Up to day 5, at day 30
Title
Time to normalization of blood levels
Description
Time to normalization of platelets (defined as >150 x109/l) and neutrophils (>2 x109/l)
Time Frame
Up to day 30
Title
Platelet nadir
Description
Lowest platelet count recorded during admission
Time Frame
Up to day 30
Title
Fever clearance time
Description
Time to temperature <37.5 for at least 48 hours
Time Frame
Up to day 30
Title
Duration of viraemia
Description
Number of days from enrollment to the first undetectable viraemia (negative in qPCR and NS1)
Time Frame
Up to day 30
Title
Area under the curve (AUC) of the serial viral load measurements during hospital stay
Description
AUC of viral load measurements during hospital stay will be reported
Time Frame
at discharge (assessed up to day 8)
Title
Patients' quality of life questionnaire score
Description
Patients' quality of life during their hospitalisation will be explored at discharge and day 30 using the EQ-5D questionnaire.
Time Frame
at discharge (assessed up to day 8) and at day 30
Other Pre-specified Outcome Measures:
Title
Change in immune cells
Description
Phenotyping CD8/4+T and NK cells will be assessed
Time Frame
Up to day 90

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients hospitalised with a clinical diagnosis of dengue and at least 1 warning sign(s) (see appendix) or severe dengue to Emergency department/inpatient wards/Intensive Care wards (ICU), Ferritin levels > 2000ng/mL ≥ 12 years of age Written informed consent or assent to participate in the study Agree to come back for 2 follow up visits around day 30 of illness (maximum 5 weeks) and at 3 months Exclusion Criteria: Pregnancy Localizing features suggesting an alternative/additional diagnosis, e.g. pneumonia, sepsis Patients taking immunosuppressive drugs or other biologics in last 1 month Patients with underlying malignancy or immunosuppression Children <12 years Have end-stage renal failure (baseline GFR < 30ml/min) Being treated for TB Taking any drug with significant interaction with anakinra The study physician judges that the patient is unlikely to attend follow up visit at around 3-4 weeks after fever onset - e.g. due to long travelling distance from the clinic
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sophie Yacoub
Phone
+84 77728736
Email
syacoub@oucru.org
First Name & Middle Initial & Last Name or Official Title & Degree
Dung Nguyen
Phone
+84 28 3924 1983
Email
CTU-Ethics@oucru.org
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sophie Yacoub
Organizational Affiliation
University of Oxford, UK
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hospital for Tropical Diseases
City
Ho Chi Minh
Country
Vietnam
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Qui Tu Phan, MD, PhD
Phone
+84 (0)2839235804
First Name & Middle Initial & Last Name & Degree
Qui T Phan, MD,PhD
First Name & Middle Initial & Last Name & Degree
Trieu T Huynh, MD,MSc
First Name & Middle Initial & Last Name & Degree
Tho V Phan, MD, Spec.II
First Name & Middle Initial & Last Name & Degree
Thuy B Duong, MD, PhD
First Name & Middle Initial & Last Name & Degree
Tam T Cao, MD,Spec.II
First Name & Middle Initial & Last Name & Degree
Diet V Tran, MD,Spec.II
First Name & Middle Initial & Last Name & Degree
Huong T Nguyen, MD
First Name & Middle Initial & Last Name & Degree
Tam T Dong, As. Prof
First Name & Middle Initial & Last Name & Degree
Nguyet M Nguyen, MD, PhD
First Name & Middle Initial & Last Name & Degree
Trung T Dinh, MD, PhD
First Name & Middle Initial & Last Name & Degree
Chanh Q Chanh, MD, MSc
First Name & Middle Initial & Last Name & Degree
Huy Q Nguyen, MD, MSc
First Name & Middle Initial & Last Name & Degree
Van T Nguyen, MD, MSC
First Name & Middle Initial & Last Name & Degree
Duyen T Huynh, MSc
First Name & Middle Initial & Last Name & Degree
Hoa T Vo, PhD
First Name & Middle Initial & Last Name & Degree
Thuan D Trong
First Name & Middle Initial & Last Name & Degree
Tran B Nguyen, Pharm.,MSc
First Name & Middle Initial & Last Name & Degree
Athimalaipet Ramanan, Prof.
First Name & Middle Initial & Last Name & Degree
Laura Rivino, As. Prof.
First Name & Middle Initial & Last Name & Degree
Eoin McKinney
First Name & Middle Initial & Last Name & Degree
Ken Smith, Prof.

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymised data of this study may be requested for publication by journals. Sharing anonymised with future similar/suitable studies will be decided by the sponsor, PIs and the authority agency where the data was collected. No identifiable information will be shared with any other person/organisation than authorized in the study.
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Anakinra in Dengue With Hyperinflammation ( AnaDen )

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