Multi-centre randomised placebo-controlled trial of corticosteroids in the prevention of coronary artery abnormalities in acute Kawasaki Disease (KD)

Completed

Conditions: Kawasaki disease (mucocutaneous lymph node syndrome)
Musculoskeletal Diseases
Kawasaki's syndrome

Registration Number: ISRCTN74427627

Lead Sponsor: niversity of Leeds (UK)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: All

Target Recruitment: 1306

Inclusion Criteria

Patients aged one month to 16 years, inclusively, who present with either of the following (1. OR 2.):
1. A history of fever for at least four days, but not more than ten days, in addition to more than or equal to four of the five following features, identified by history and/or at presentation:
a. Oral mucosal changes ? any one of:
i. Redness, dryness, cracking, fissuring, peeling or bleeding of lips, or
ii. Diffuse redness of oral and pharyngeal mucosae, or
iii. Strawberry tongue (e.g. deep redness, prominent fungiform papillae)
b. Extremity changes ? redness of palms and soles, and/or induration (swelling) of hands and feet
c. Skin rash ? any rash that is non-vesicular and non-bullous
d. Conjunctivitis ? bilateral and non-purulent
e. Anterior cervical lymphadenopathy (any)

2. A history of fever for at least five days, but not more than ten days, in addition to three of the five features listed above AND any one of:
a. Serum C-Reactive Protein (CRP) more than or equal to 30 mg/l, or
b. Serum Erythrocyte Sedimentation Rate (ESR) more than or equal to 40 mm/hour, or
c. Plasma viscosity more than or equal to 1.7 mPa/s

Not all of these clinical features need be present at enrolment or at a single point in time.

'Fever' is considered to be pyrexia by history (e.g. tactile assessment by parent) OR by direct measurement. Whenever measured, fever is defined as a temperature of more than or equal to 38.0 °C (100.4 °F), determined by any method (e.g. oral, rectal, tympanic or axillary). A parental impression of pyrexia by tactile assessment alone can be taken as a day of fever, regardless of any measured temperature. The first day of fever is taken as the day on which the parent or guardian reports that the child first had a fever, either by history or recorded measurement.

Exclusion Criteria

1. Fever for more than or equal to 11 days
2. Previous diagnosis of KD (e.g. recurrent disease or a second discrete symptomatic presentation of KD)
3. Clinical features suggesting disease other than KD, including any of:
a. Exudative conjunctivitis
b. Exudative pharyngitis
c. Exudative tonsillitis
d. Discrete intra-oral ulcerations or lesions
e. Bullous or vesicular rash
f. Hepatosplenomegaly and generalized adenopathy (e.g. inguinal and cervical)
4. Known or suspected acute diagnosis of:
a. Viral infection ? adenovirus, enteroviruses, Epstein-Barr Virus (EBV, infectious mononucleosis), CytoMegaloVirus (CMV), measles
b. Bacterial infection ? bacterial cervical adenitis, scarlet fever, staphylococcal scalded skin syndrome, toxic shock syndrome (S. aureus or group A streptococcus)
c. Rickettsial infection - leptospirosis, Rocky Mountain spotted fever
d. Drug hypersensitivity reaction
e. Stevens-Johnson Syndrome (SJS)
f. Juvenile Idiopathic Arthritis (JIA)
g. Leukaemia, lymphoma or other malignancy
h. Mercury hypersensitivity reaction (acrodynia)
5. Significant positive blood culture (single, non-contaminant organism)
6. Throat swab culture positive for group A streptococcus (Streptococcus pyogenes)
7. Positive Anti-Streptolysin-O titer (ASO titer)
8. Severe Congestive Heart Failure (CHF), with signs/symptoms present
9. Chronic renal failure
10. Liver failure
11. Severe systemic infection
12. Contraindication to systemic corticosteroid therapy:
a. History of allergic reaction (hypersensitivity) to intravenous methylprednisolone or one of its components
b. Severe allergy to an oral or intramuscular corticosteroid
c. Current treatment with any of: amphotericin, carbamazepine, cyclosporine, methotrexate
d. Active varicella infection
e. Exposure to case of varicella within the previous 21 days
13. Current oral, intravenous or intramuscular corticosteroid treatment
14. History of allergic reaction or severe systemic response to any human immune globulin preparation
15. Known Immunoglobulin A (IgA) deficiency or agammaglobulinaemia (antibody immune deficiency)
16. Lack of written informed parental consent
17. Enrolment in another study that might affect treatment delivery or efficacy or clinical follow-up

Administration of IVIG prior to enrolment does not necessarily exclude the child from enrolment in the trial. The presence of CA aneurysms on baseline echocardiogram is also not an exclusion criterion. However, any aneurysm must be documented by a study cardiologist.