Clinical trial NCT00132080: Trial of Pulse Steroid Therapy in Kawasaki Disease--Pediatric Heart Network
Official title: Trial of Pulse Steroid Therapy in Kawasaki Disease (A Trial Conducted by the Pediatric Heart Network)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Cardiovascular Diseases
Heart Diseases
Infection
Coronary Aneurysm
Lead sponsor: Carelon Research
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Pediatric Heart Network
First posted: 2005-08-19
Enrollment: 199
Sex: ALL
Minimum age (years): 6
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The primary endpoint is coronary artery diameter, normalized for body surface area, 5 weeks after randomization. Secondary endpoints include duration of fever, CRP levels, and adverse events.

Detailed description: BACKGROUND:

Kawasaki Disease (KD) is an inflammatory vasculitis of unknown etiology that affects infants and children and can cause coronary artery aneurysms. Standard therapy consists of 2 gm/kg of intravenous immune globulin plus high-dose aspirin in the acute phase, and low-dose aspirin in the convalescent phase. Some children do not respond to this therapy, and some children go on to develop coronary artery aneurysms in spite of aggressive treatment. This led to the design of this randomized controlled trial to compare a single dose of intravenous steroids vs. placebo on the background of standard therapy. Recruitment began in December, 2002 and ended in December, 2004 with nearly 200 patients randomized.

DESIGN NARRATIVE:

This is a randomized controlled trial to compare a single dose of intravenous steroids vs. placebo on the background of standard therapy

Eligibility criteria: * Fever persisting at least 4 days and the presence of at least 4 of the following 5 principal features:

  1. Changes in extremities: Acute changes include erythema and edema of hands and feet; Convalescent changes include membranous desquamation of fingertips
  2. Polymorphous exanthema
  3. Bilateral, painless bulbar conjunctival injection without exudates
  4. Changes in lips and oral cavity: Erythema and cracking of lips, strawberry tongue, diffuse injection of oral and pharyngeal mucosae
  5. Cervical lymphadenopathy ( 1.5 cm in diameter), usually unilateral;

OR

* Patients with at least four days of fever and coronary artery disease, defined as either:

  1. Having a z-score in either the proximal right coronary artery or the proximal left anterior descending coronary artery of \> 2.5 detected by 2-dimensional echocardiography, as well as:
* For patients under six months of age, at least two principal criteria
* For patients at least six months of age, at least three principal criteria. 2. Meeting Japanese Ministry of Health criteria for coronary aneurysm defined as an internal lumen diameter of \>3 mm in children less than 5 years of age or \>4 mm in children 5 years of age and older, in either the proximal right coronary artery or the proximal left anterior descending coronary artery and at least one principal criterion.

AND Enrollment within ten days of the onset of illness, with Day 1 defined as the first day of fever AND Informed consent of parents and assent of children who are older than age 7 years and capable of understanding or according to institutional guidelines.

Primary outcomes:
measure: Compare the effect of IVMP plus IVIG to IVIG alone on coronary artery outcomes
timeFrame: Measured 5 weeks post-randomization
Secondary outcomes:
measure: Occurrence of CA aneurysms; individual z scores of the LMCA, proximal RCA, and proximal LAD CA at 1 and 5 weeks; changes in absolute coronary dimensions for all CA segments from baseline to 1 and 5 weeks after randomization
timeFrame: Measured 5 weeks post-randomization
Other outcomes:
Locations:
Study officials:
affiliation: New England Research Institutes, Watertown, MA
name: Lynn Sleeper, ScD.
role: PRINCIPAL_INVESTIGATOR
References:
citation: Printz BF, Sleeper LA, Newburger JW, Minich LL, Bradley T, Cohen MS, Frank D, Li JS, Margossian R, Shirali G, Takahashi M, Colan SD; Pediatric Heart Network Investigators. Noncoronary cardiac abnormalities are associated with coronary artery dilation and with laboratory inflammatory markers in acute Kawasaki disease. J Am Coll Cardiol. 2011 Jan 4;57(1):86-92. doi: 10.1016/j.jacc.2010.08.619.
citation: Sleeper LA, Minich LL, McCrindle BM, Li JS, Mason W, Colan SD, Atz AM, Printz BF, Baker A, Vetter VL, Newburger JW; Pediatric Heart Network Investigators. Evaluation of Kawasaki disease risk-scoring systems for intravenous immunoglobulin resistance. J Pediatr. 2011 May;158(5):831-835.e3. doi: 10.1016/j.jpeds.2010.10.031. Epub 2010 Dec 18.
citation: Baker AL, Lu M, Minich LL, Atz AM, Klein GL, Korsin R, Lambert L, Li JS, Mason W, Radojewski E, Vetter VL, Newburger JW; Pediatric Heart Network Investigators. Associated symptoms in the ten days before diagnosis of Kawasaki disease. J Pediatr. 2009 Apr;154(4):592-595.e2. doi: 10.1016/j.jpeds.2008.10.006. Epub 2008 Nov 28.
citation: Newburger JW, Sleeper LA, McCrindle BW, Minich LL, Gersony W, Vetter VL, Atz AM, Li JS, Takahashi M, Baker AL, Colan SD, Mitchell PD, Klein GL, Sundel RP; Pediatric Heart Network Investigators. Randomized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. N Engl J Med. 2007 Feb 15;356(7):663-75. doi: 10.1056/NEJMoa061235.