Non Inferiority KawasakI Trial With Anakinra (NIKITA)

November 19, 2024 updated by: Gabriele Simonini, Meyer Children's Hospital IRCCS

A Randomized, Controlled, Open-label, Non Inferiority KawasakI Trial With Anakinra

This is a multicenter, open-label, randomized, controlled, interventional trial followed by a long-term observational extension period in patients with Kawasaki Disease (KD) to be treated eitherwith endovenous Immunoglobulins (IVIG-standard treatment) versus anakinra

Aim of the study: to demonstrate that anakinra is non-inferior to IVIG in KD, in terms of fever control in the acute phase and development of coronary artery dilation/aneurisms (CAA) within one year from the onset.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a multicenter national, open label, randomized, controlled, interventional trial followed by a long-term observational extension period. This is a non-inferiority study Patients who fulfill the eligibility criteria and whose parent/carer (legal representative) has provided informed consent will be randomized 1:1 to receive either

  1. IVIG 2g/kg administered in 10-12 hours as per local standard of care (standard treatment) OR
  2. Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day (investigational treatment)

PLUS Aspirin (ASA) 50mg/kg QID until 36 hours from fever disappearance, then switched to low-dose (3-5 mg/Kg once a day) as per standard of care

Study Type

Interventional

Enrollment (Estimated)

38

Phase

  • Phase 4

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

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

  • Child

Accepts Healthy Volunteers

No

Description

Inclusion Criteria

  1. KD defined in at least one of the three following ways as per American Heart Association (AHA) criteria: Fever for at least 5 days in addition to 4 of the following 5 clinical criteria:

    • bilateral non-purulent conjunctivitis
    • cervical lymphadenopathy
    • polymorphous skin rash
    • changes in lips or mucosa (strawberry tongue, red cracked lips, diffuse erythematous oropharynx)
    • extremity changes (erythema, oedema of palms and soles in initial phase, and at convalescent stage skin peeling)
  2. less than 5 days of fever but all 5 clinical criteria above

  3. incomplete KD cases defined as:

    • children/adolescents (>1 year old) with fever greater than or equal to 5 days AND at least 2 other compatible clinical criteria as listed above;
    • OR infants ≤ 1 year old with fever greater than or equal to 7 days without other explanation;

    AND for both age groups, CRP ≥30 mg/L or erythrocyte sedimentation rate (ESR) ≥40 mm/hr (or both) AND for both age groups EITHER the presence of any 3 or more of: anaemia for age (haemoglobin < lower limit of normal reference range for local laboratory); platelet count ≥450,000/L or <140,000/L; albumin <30 g/L; elevated ALT (> upper limit of normal reference range for local laboratory); white cell count ≥15,000/L; urine ≥10 white blood cells per high power field iv.

    OR abnormal echocardiogram compatible with KD but without established CAA, with ≥ 3 of the following suggestive features: decreased left ventricular function, mitral regurgitation, pericardial effusion, or dilated but non-aneurysmal coronary arteries (internal diameter 2≤Z<2.5; and not meeting the exclusion criteria for aneurysmal change as defined below).

  4. To be enrolled children need to show persistent fever ≤7 days
  5. Written informed consent from an appropriate legal representative(s), and assent from patients older than 7 years

Exclusion Criteria

  1. Patients with KD and already established coronary artery aneurysms (CAA), as per AHA definition, at screening.
  2. Clinical picture consistent with Kawasaki Shock Syndrome (KDSS) or Macrophage Activation Syndrome (MAS) OR Multisystem Inflammatory Syndrome in Children (MIS-C)
  3. History or evidence of any previous heart disease
  4. Known hypersensitivity to anakinra, IVIG and ASA or any medical condition that contraindicates the use of these treatments
  5. Patients with KD receiving IVIG, corticosteroids, immunosuppressants, biologic treatments at the time of screening

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: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Anakinra
Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day
Drug: Anakinra

Patients who fulfill the eligibility criteria a will be randomized 1:1 to receive either

  1. IVIG 2g/kg administered in 10-12 hours as per local standard of care (standard treatment) OR
  2. Anakinra 2mg/kg intravenously, max 100 mg/dose 4 times/day (investigational treatment)

Patients showing fever, between 36 hours and 72 hours from the end of first line treatment will be considered failures. Failures from the investigational treatment arm will receive a dose of IVIG and they will drop from the study.

Children who remained afebrile between the 36th and 72nd hour will be considered as responders, and they will proceed into the study.

Patients in the standard treatment arm will continue ancillary treatment and follow-up .

Patients in the investigational treatment arm will enter the tapering phase.

Other Names:
  • Kineret
Active Comparator: Intravenous immunoglobulins
IVIG 2g/kg administered in 10-12 hours as per local standard of care
Drug: Intravenous Immunoglobulins, Human
see previous section
Other Names:
  • IVIG

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Number of patients with treatment response in both treatment arms
Time Frame: 12 months
Response rate
12 months
Number of patients with CAA (as per Z-scores) at the end of the study period in both treatment arms
Time Frame: 12 months
CAA rate in both arms. CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
12 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Adverse event and severe adverse event developed during the study and follow/up period
Time Frame: 24 months
Medical Dictionary for Regulatory Activities (MeDRA) will be used for the description of adverse events (AEs), according to the regulatory requirements
24 months
Cumulative drug exposure (mg/kg/day)
Time Frame: 12 months
Calculated for both iv e sc administration
12 months
Number of days with fever in both treatment arms
Time Frame: 90 days
Fever as defined as T>38°C
90 days
Time to reach CRP values<50% from the highest value and to normalize it in both treatment arms (days)
Time Frame: 90 days
CRP values expressed in mg/dL
90 days
Time to normalize coronary artery abnormalities (days)
Time Frame: 90 days
CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
90 days
Severity of coronary artery abnormalities (as per Z-score) at the end of follow-up
Time Frame: 24 months
CAAs will be classified in accordance with the scheme based on Z scores proposed by AHA. No coronary involvement with Z score <2, dilation only with Z score > 2 to <2.5 or if initially <2 with a decrease during follow-up ≥1 3, small aneurysm with Z score ≥2.5 to <5, medium aneurysm with Z score ≥5 to <10 and absolute dimension <8 mm and large or giant aneurysm with Z score ≥10, or absolute dimension ≥8 mm
24 months
Length of hospitalization in both treatment arms (days)
Time Frame: 90 days
Defined by days of hospitalization from disease onset to discharge
90 days
Time to stop anakinra (days)
Time Frame: 90 days
From the first administration iv to the last sc
90 days

Collaborators and Investigators

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

Sponsor

Meyer Children's Hospital IRCCS

Collaborators

IRCCS Burlo Garofolo
Asst Degli Spedali Civili Di Brescia

Investigators

  • Principal Investigator: Gabriele Simonini, Prof, Meyer Children's Hospital IRCCS

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 (Estimated)

April 1, 2025

Primary Completion (Estimated)

April 1, 2026

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

November 1, 2024

First Submitted That Met QC Criteria

November 18, 2024

First Posted (Actual)

November 20, 2024

Study Record Updates

Last Update Posted (Estimated)

November 21, 2024

Last Update Submitted That Met QC Criteria

November 19, 2024

Last Verified

November 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • NIKITA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

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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