Kawasaki Disease MedDRA version: 20.0 Level: PT Classification code 10023320 Term: Kawasaki's disease System Organ Class: 10047065 - Vascular disorders
Conditions
Interventions
Product Name: Prednisolone (Tablet 1mg)
Pharmaceutical Form: Tablet
INN or Proposed INN: Prednisolone
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 1-
Product Na
Sponsors
MRC CTU at UCL
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Aged 30 days (post-natal age) to 15 years inclusive, and below the country-specific age of consent for the duration of the trial 2. KD defined in at least one of the three following ways (a) as per American Heart Association (AHA) criteria [1]: namely fever for at least 5 days in addition to 4 of the following 5 clinical criteria: I. bilateral non purulent conjunctivitis ii. cervical lymphadenopathy iii. polymorphous skin rash iv. changes in lips or mucosa (strawberry tongue, red cracked lips, diffuse erythematous oropharynx) v. extremity changes (erythema, oedema of palms and soles in initial phase, and at convalescent stage skin peeling) (b) OR less than 5 days of fever but all 5 clinical criteria above (c) OR incomplete KD cases, as per a modified*AHA definition [1], namely: I. 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 ii. CRP =30 mg/L or erythrocyte sedimentation rate (ESR) =40 mm/hr (or both) AND for both age groups iii. EITHER the presence of any 3 or more of: anaemia for age (haemoglobin upper limit of normal reference range for local laboratory); white cell count =15 x10?/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=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Disease-related exclusions: 1. This diagnosis is a second or further episode of KD. 2. Already established CAA at screening. 3. Severe Congestive Heart Failure or cardiogenic shock defined as the presence of hypotension and shock requiring the initiation of volume expanders. 4. Known congenital coronary artery abnormality that would impair assessment of the primary endpoint. 5. Suspected macrophage activation syndrome. Exclusions related to medications: 6. Started IVIG more than 24 hours prior to randomisation. 7. Known hypersensitivity to prednisolone or methylprednisolone. 8. Current oral, intravenous or intramuscular corticosteroid treatment for more than 3 days in previous 7 days prior to randomisation. 9. History of previous severe reaction to any human immune globulin preparation. Exclusions related to general health or other issues: 10. Active varicella zoster virus infection; or known exposure to a case of varicella within the previous 21 days prior to randomisation if known to be non-immune. 11. Co-enrolment in another study/trial of an investigative medicinal product.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Does the combination of corticosteroid and IVIG/aspirin reduce the rate of heart complications in children/adolescents with Kawasaki disease across Europe compared with IVIG/aspirin alone? ;Secondary Objective: Does the combination of corticosteroid and IVIG/aspirin reduce the length of stay in hospital for children/adolescents with Kawasaki disease, and do their blood test results improve faster compared with IVIG/aspirin alone? What side effects do children/adolescents get with corticosteroids or other therapies to treat Kawasaki disease? Is the combination of corticosteroid therapy and IVIG/aspirin a cost effective treatment for the management of Kawasaki disease? ;Primary end point(s): KD-CAAP will have two co-primary outcome measures: Any CAA (definition below) documented within the 12 weeks of trial follow-up (to assess overall effectiveness of the strategy of immediate corticosteroids in preventing CAA, expecting that some patients will receive rescue treatment before reaching this endpoint in both randomised groups). An average estimate across weeks 1, 2, and 6 of the maximum of the Z-score of the internal diameters of the proximal right coronary artery or left anterior descending coronary artery, adjusting for rescue treatment (to assess the direct efficacy of corticosteroids). ;Timepoint(s) of evaluation of this end point: Weeks 1, 2, 6 and 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Efficacy At each of weeks 1, 2, 6 and 12 individually, the maximum of the Z-score of the internal diameters of the proximal right coronary artery or left anterior descending coronary artery. Any CAA defined using a stricter definition of a luminal internal diameter Z-score of =2.5 alone documented within the 12 weeks of trial follow-up Receipt of rescue treatment. Receipt of second dose of IVIG. Duration of fever after enrolment (time to temperature <38°C). Daily serum concentrations of CRP from days 1-5, and at 1 and 2 weeks after enrolment, and time to normalisation of CRP (=10mg/L). Duration of hospitalisation. Safety Serious adverse events including deaths. Grade 3 or 4 adverse events. Clinical adverse events of any grade judged related to IVIG, aspirin or corticosteroids. ;Timepoint(s) of evaluation of this end point: Days 1, 2, 3, 4, 5 and weeks 1, 2, 6, 12 | — |
Countries
Austria, Belgium, Czech Republic, Estonia, Finland, France, Germany, Greece, Ireland, Italy, Netherlands, Poland, Spain, Sweden, United Kingdom
Contacts
Public ContactClinical Trial Manager
Cara Purvis
Outcome results
None listed