The Kawasaki Disease Comparative Effectiveness (KIDCARE) trial: A phase III, randomized trial of second intravenous immunoglobulin versus infliximab for resistant Kawasaki disease

Contemp Clin Trials. 2019 Apr:79:98-103. doi: 10.1016/j.cct.2019.02.008. Epub 2019 Mar 3.

Abstract

Background: Although intravenous immunoglobulin (IVIG) is effective therapy for Kawasaki disease (KD), the most common cause of acquired heart disease in children, 10-20% of patients are IVIG-resistant and require additional therapy. This group has an increased risk of coronary artery aneurysms (CAA) and there has been no adequately powered, randomized clinical trial in a multi-ethnic population to determine the optimal therapy for IVIG-resistant patients.

Objectives: The primary outcome is duration of fever in IVIG-resistant patients randomized to treatment with either infliximab or a second IVIG infusion. Secondary outcomes include comparison of inflammatory markers, duration of hospitalization, and coronary artery outcome. An exploratory aim records parent-reported outcomes including signs, symptoms and treatment experience.

Methods: The KIDCARE trial is a 30-site randomized Phase III comparative effectiveness trial in KD patients with fever ≥36 h after the completion of their first IVIG treatment. Eligible patients will be randomized to receive either a second dose of IVIG (2 g/kg) or infliximab (10 mg/kg). Subjects with persistent or recrudescent fever at 24 h following completion of the first study treatment will cross-over to the other treatment arm. Subjects will exit the study after their first outpatient visit (5-18 days following last study treatment). The parent-reported outcomes, collected daily during hospitalization and at home, will be compared by study arm.

Conclusion: This trial will contribute to the management of IVIG-resistant patients by establishing the relative efficacy of a second dose of IVIG compared to infliximab and will provide data regarding the patient/parent experience of these treatments.

Keywords: IVIG; IVIG-resistance; Infliximab; Kawasaki disease.

Publication types

  • Clinical Trial Protocol
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Child
  • Child, Preschool
  • Clinical Trials, Phase III as Topic
  • Comparative Effectiveness Research
  • Cross-Over Studies
  • Drug Resistance
  • Echocardiography
  • Female
  • Fever* / drug therapy
  • Fever* / etiology
  • Humans
  • Immunoglobulins, Intravenous* / administration & dosage
  • Immunoglobulins, Intravenous* / adverse effects
  • Immunoglobulins, Intravenous* / therapeutic use
  • Infant
  • Inflammation Mediators / analysis
  • Infliximab* / administration & dosage
  • Infliximab* / adverse effects
  • Infliximab* / therapeutic use
  • Length of Stay
  • Male
  • Mucocutaneous Lymph Node Syndrome* / complications
  • Mucocutaneous Lymph Node Syndrome* / drug therapy
  • Multicenter Studies as Topic
  • Randomized Controlled Trials as Topic

Substances

  • Immunoglobulins, Intravenous
  • Inflammation Mediators
  • Infliximab