Multi-center Prospective Randomized Control Trail of High Dose Aspirin in Acute Stage of Kawasaki Disease

Kawasaki Disease Clinical Trial

Official title:

Multi-center Prospective Randomized Control Trail of High Dose Aspirin in Acute Stage of Kawasaki Disease

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02359643
• Other study ID #: Kawasaki Disease
• Status: Enrolling by invitation
• Phase: N/A
• First received: January 5, 2015
• Last updated: January 31, 2016
• Start date: May 2013
• Est. completion date: April 2017

Study information

• Verified date: May 2013
• Source: Chang Gung Memorial Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Kawasaki disease (KD) is an acute multi-system vasculitis syndrome of unknown etiology occurring mostly in infants and children younger than 5 years of age. In developed countries, it is the leading cause of acquired heart disease in children. However, KD remains a mysterious disease.

Single high dose intravenous immunoglobulin (IVIG, 2gm/kg) and aspirin are standard treatment for KD. Aspirin have been prescribed in treatment of KD for decade even earlier than usage of IVIG. High dose aspirin mainly act as anti-inflammation, while low dose aspirin as anti-platelet. IVIG may play most of the role of anti-inflammation in acute stage of KD. Hsieh et al. reported that KD without high dose aspirin had the same treatment response after IVIG. Therefore it is still unclear about the necessarily of high dose aspirin in acute stage of KD.

This study was conduct to investigate the role of high dose aspirin in acute stage of KD via a multi-center randomized control trail, and we plan to achieve the followings till year 2017:

1. Enroll 300 KD patients from multiple medical centers . Randomize group patients as group 1: with high dose aspirin (more than 30/mg/kd/day) until fever subsided and shift to low dose aspirin (3-5mg/kg/day, N=150); and group 2: without high dose aspirin during acute febrile stage, only use low dose aspirin (N=150).

2. Compare data including fever days, admission duration, laboratory data (CBC/DC, GOT/GPT, BUN/Cr, Alb, ESR, CRP, 2D echo), IVIG treatment response and CAL formation rate (followed at least 1 year).

Description:

All subjects are children who fulfilled the criteria for KD and who are treated with IVIG at each hospital after informed contents are obtained. The patients are initially treated with a single dose of IVIG (2 g/kg) during a 12-hour period.

Principal clinical features of KD that occur in the acute stage within 5 days of the onset of fever will be recorded. After the informed content from the parents, PB samples will be obtained before IVIG treatment (pre-IVIG, KD1), within 3 days after complete initial IVIG treatment (post-IVIG, KD2) as the acute stage samples and then 1 month, 6 month and 12 month followed-up as subacute/convalescent stage samples. CAL was defined as the internal diameter being at least 3 mm of the coronary artery (4 mm if the subject was over the age of 5 years) or the internal diameter of a segment at least 1.5 times as large as that of an adjacent segment by echocardiogram.

High dose aspirin will be given (> 30 mg/kg/day) until the fever subsided at group 1 randomly. After fever subside (<38C, for 48 hours) low-dose aspirin (3-5 mg/kg/day) will be prescribed for all patients until all signs of inflammation resolved in both group 1 and 2.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 300
• Est. completion date: April 2017
• Est. primary completion date: April 2017
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria: (both 1 and 2)

1. All subjects are children who fulfilled the criteria for Kawasaki Disease (American Heart Association criteria).

1. Fever > 5 days, and 4 of the 5 following symptoms

2. Diffuse mucosal inflammation (strawberry tongue, dry and fissured lips)

3. Bilateral non-purulent conjunctivitis,

4. Dysmorphous skin rashes,

5. Indurative angioedema over the hands and feet

6. Cervical lymphadenopathy. (One or more nodule at lease 1.5 cm in diameter) 2. KD patients are treated with IVIG at each hospital after informed contents are obtained.

Exclusion Criteria:

1. Patients whose symptoms did not full fit the Kawasaki Disease criteria.

2. Had an acute fever for < 5 days and >10 days

3. Incomplete collection of each followed-up data (CBC/DC, GOT/GPT, BUN/Cr, Albumin, ESR, C-Reactive Protein, 2D echocardiography)

4. IVIG treatment at other hospital before refers to study centers.

5. Treatment with corticosteroids, other than inhaled forms, in the previous 2 weeks before enrollment;

6. The presence of a disease known to mimic Kawasaki disease.

7. Previous diagnosis of Kawasaki disease

8. Inability to take aspirin

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Kawasaki Disease
• Mucocutaneous Lymph Node Syndrome

Intervention

Drug:
• Aspirin
This study was conduct to investigate the role of high dose aspirin in acute stage of KD via a multi-center randomized control trail, and we plan to achieve the followings in the coming 4 years: Enroll 300 KD patients from multiple medical centers of Taiwan and China in 4 years. Randomize group patients as group 1: with high dose aspirin (more than 30/mg/kd/day) until fever subsided and shift to low dose aspirin (3-5mg/kg/day, N=150); and group 2: without high dose aspirin during acute febrile stage, only use low dose aspirin (N=150). Compare data including fever days, admission duration, laboratory data (CBC/DC, GOT/GPT, BUN/Cr, Alb, ESR, CRP, 2D echo), IVIG treatment response and CAL formation rate (followed at least 1 year).

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Chang Gung Memorial Hospital

References & Publications (2)

Chen CH, Lin LY, Yang KD, Hsieh KS, Kuo HC. Kawasaki disease with G6PD deficiency--report of one case and literature review. J Microbiol Immunol Infect. 2014 Jun;47(3):261-3. doi: 10.1016/j.jmii.2012.05.002. Epub 2012 Jun 23. — View Citation

Hsieh KS, Weng KP, Lin CC, Huang TC, Lee CL, Huang SM. Treatment of acute Kawasaki disease: aspirin's role in the febrile stage revisited. Pediatrics. 2004 Dec;114(6):e689-93. Epub 2004 Nov 15. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To assess total hospital day		5-10 days	No
Secondary	To assess total fever duration		5-10 days	No
Secondary	To assess how many times of intramenous immunoglobulin (IVIG) treatment	IVIG resistance: more than 2 times of IVIG (2gm/kg); or IVIG responsive: only treatment with one time of IVIG (2gm/kg)	21 days	No
Secondary	To examine whether coronary artery lesion formation (CAL)	CAL was defined as the internal diameter being at least 3 mm of the coronary artery (4 mm if the subject was over the age of 5 yr) or the internal diameter of a segment at least 1.5 times as large as that of an adjacent segment by echocardiogram	6-8 weeks	No