Anakinra in Dengue With Hyperinflammation ( AnaDen )

March 19, 2024 updated by: Oxford University Clinical Research Unit, Vietnam

Anakinra for Dengue Patients With Hyperinflammation - a Randomized Double-blind Placebo-controlled Trial

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

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Estimated)

160

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Vietnam
      • Ho Chi Minh, Vietnam
        • Recruiting
        • Hospital for Tropical Diseases
        • Contact:
          • Qui Tu Phan, MD, PhD
          • Phone Number: +84 (0)2839235804
        • Principal Investigator:
          • Qui T Phan, MD,PhD
        • Sub-Investigator:
          • Trieu T Huynh, MD,MSc
        • Sub-Investigator:
          • Tho V Phan, MD, Spec.II
        • Sub-Investigator:
          • Thuy B Duong, MD, PhD
        • Sub-Investigator:
          • Tam T Cao, MD,Spec.II
        • Sub-Investigator:
          • Diet V Tran, MD,Spec.II
        • Sub-Investigator:
          • Huong T Nguyen, MD
        • Sub-Investigator:
          • Tam T Dong, As. Prof
        • Sub-Investigator:
          • Nguyet M Nguyen, MD, PhD
        • Sub-Investigator:
          • Trung T Dinh, MD, PhD
        • Sub-Investigator:
          • Chanh Q Chanh, MD, MSc
        • Sub-Investigator:
          • Huy Q Nguyen, MD, MSc
        • Sub-Investigator:
          • Van T Nguyen, MD, MSC
        • Sub-Investigator:
          • Duyen T Huynh, MSc
        • Sub-Investigator:
          • Hoa T Vo, PhD
        • Sub-Investigator:
          • Thuan D Trong
        • Sub-Investigator:
          • Tran B Nguyen, Pharm.,MSc
        • Sub-Investigator:
          • Athimalaipet Ramanan, Prof.
        • Sub-Investigator:
          • Laura Rivino, As. Prof.
        • Sub-Investigator:
          • Eoin McKinney
        • Sub-Investigator:
          • Ken Smith, Prof.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

12 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Sequential Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
The control group will be formed of 80 dengue patients with warning signs or severe dengue receiving placebo.
Drug: Placebo

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

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)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) within 4 days
Time Frame: baseline, up to day 4
Change in mSOFA score over 4 days after randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
baseline, up to day 4

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: Up to day 30
Number of death up to day 30
Up to day 30
Change in modified Sequential Organ Failure Assessment score (mSOFA core, modified for limited resource settings and dengue) at day 7
Time Frame: baseline, day 7
Change in mSOFA score at day 7 post randomization (min score= 0, max score = 24, higher scores mean worse outcomes)
baseline, day 7
Number of days treated in Intensive care unit (ICU)
Time Frame: Up to day 30
Number of days treated in ICU
Up to day 30
Number of days treated in hospital
Time Frame: Up to day 30
Number of days treated in hospital
Up to day 30
Number of participants with Serious Adverse Events (SAEs)
Time Frame: Day 1-5 and Day 6-30
Number of participants having SAEs within 2 time-periods, 1- 5 days and 6-30 days
Day 1-5 and Day 6-30
Number of Adverse Events (AEs) per participant
Time Frame: Up to day 30
Number of AEs per individual
Up to day 30
Change in Platelets count
Time Frame: Up to day 5, at day 30
Change in blood levels (Platelets) over 5 days following randomization and at day 30
Up to day 5, at day 30
Change in neutrophils count
Time Frame: Up to day 5, at day 30
Change in blood levels (neutrophils) over 5 days following randomization and at day 30
Up to day 5, at day 30
Change of ALT levels
Time Frame: Up to day 5, at day 30
Change in blood levels (ALT) over 5 days following randomization and at day 30
Up to day 5, at day 30
Change of Ferritin levels
Time Frame: Up to day 5, at day 30
Change in blood levels (Ferritin) over 5 days following randomization and at day 30
Up to day 5, at day 30
Change of CRP levels
Time Frame: Up to day 5, at day 30
Change in blood levels (CRP) over 5 days following randomization and at day 30
Up to day 5, at day 30
Time to normalization of blood levels
Time Frame: Up to day 30
Time to normalization of platelets (defined as >150 x109/l) and neutrophils (>2 x109/l)
Up to day 30
Platelet nadir
Time Frame: Up to day 30
Lowest platelet count recorded during admission
Up to day 30
Fever clearance time
Time Frame: Up to day 30
Time to temperature <37.5 for at least 48 hours
Up to day 30
Duration of viraemia
Time Frame: Up to day 30
Number of days from enrollment to the first undetectable viraemia (negative in qPCR and NS1)
Up to day 30
Area under the curve (AUC) of the serial viral load measurements during hospital stay
Time Frame: at discharge (assessed up to day 8)
AUC of viral load measurements during hospital stay will be reported
at discharge (assessed up to day 8)
Patients' quality of life questionnaire score
Time Frame: at discharge (assessed up to day 8) and at day 30
Patients' quality of life during their hospitalisation will be explored at discharge and day 30 using the EQ-5D questionnaire.
at discharge (assessed up to day 8) and at day 30

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in immune cells
Time Frame: Up to day 90
Phenotyping CD8/4+T and NK cells will be assessed
Up to day 90

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Investigators

  • Principal Investigator: Sophie Yacoub, University of Oxford, UK

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 2, 2023

Primary Completion (Estimated)

December 31, 2025

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

October 19, 2022

First Submitted That Met QC Criteria

November 3, 2022

First Posted (Actual)

November 10, 2022

Study Record Updates

Last Update Posted (Actual)

March 21, 2024

Last Update Submitted That Met QC Criteria

March 19, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 60DX

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD 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.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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