Study protocol for a phase III multicentre, randomised, open-label, blinded-end point trial to evaluate the efficacy and safety of immunoglobulin plus cyclosporin A in patients with severe Kawasaki disease (KAICA Trial)

BMJ Open

Volumn 5, Issue 12, 2015, Pages

  Aoyagi, Reiko ^a   Hamada, Hiromichi ^b   Sato, Yasunori ^a   Suzuki, Hiroyuki ^c   Onouchi, Yoshihiro ^d   Ebata, Ryota ^d   Nagashima, Kengo ^a   Terauchi, Moe ^a   Terai, Masaru ^b   Hanaoka, Hideki ^a   Hata, Akira ^d  

^a CHIBA UNIVERSITY HOSPITAL   (Japan)

^b Tokyo Women s Medical University   (Japan)

^c WAKAYAMA MEDICAL UNIVERSITY   (Japan)

^d CHIBA UNIVERSITY GRADUATE SCHOOL OF MEDICINE   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLSALICYLIC ACID; CYCLOSPORIN A; IMMUNOGLOBULIN; CALCINEURIN INHIBITOR; CYCLOSPORIN;

ARTICLE; CLINICAL PROTOCOL; DISEASE SEVERITY; DRUG EFFICACY; DRUG MEGADOSE; DRUG SAFETY; HUMAN; MUCOCUTANEOUS LYMPH NODE SYNDROME; MULTICENTER STUDY (TOPIC); OPEN STUDY; PHASE 3 CLINICAL TRIAL (TOPIC); PROSPECTIVE STUDY; RANDOMIZED CONTROLLED TRIAL (TOPIC); CLINICAL TRIAL; COMBINATION DRUG THERAPY; CONTROLLED STUDY; FEMALE; INFANT; JAPAN; MALE; METHODOLOGY; MULTICENTER STUDY; PHASE 3 CLINICAL TRIAL; PRESCHOOL CHILD; PROPORTIONAL HAZARDS MODEL; RANDOMIZED CONTROLLED TRIAL; TREATMENT OUTCOME;

ASPIRIN; CALCINEURIN INHIBITORS; CHILD, PRESCHOOL; CYCLOSPORINE; DRUG THERAPY, COMBINATION; FEMALE; HUMANS; IMMUNOGLOBULINS, INTRAVENOUS; INFANT; JAPAN; MALE; MUCOCUTANEOUS LYMPH NODE SYNDROME; PROPORTIONAL HAZARDS MODELS; RESEARCH DESIGN; TREATMENT OUTCOME;

EID: 84960122871     PISSN: None     EISSN: 20446055     Source Type: Journal    
DOI: 10.1136/bmjopen-2015-009562     Document Type: Article

References (36)

1. Kawasaki T. Acute febrile mucocutaneous syndrome with lymphoid involvement with specific desquamation of the fingers and toes in children. Arerugi 1967;16:178.
2. Burns JC, Glodé MP. Kawasaki syndrome. Lancet 2004;364:533-44.
3. Nakamura Y, Yashiro M, Uehara R, et al. Epidemiologic features of Kawasaki disease in Japan: Results of the 2007-2008 nationwide survey. J Epidemiol 2010;20:302.
4. Furusho K, Kamiya T, Nakano H, et al. High-dose intravenous gammaglobulin for Kawasaki disease. Lancet 1984;324:1055-8.
5. Newburger JW, Takahashi M, Burns JC, et al. The treatment of Kawasaki syndrome with intravenous gamma globulin. N Engl J Med 1986;315:341-7.
6. Newburger JW, Takahashi M, Beiser AS, et al. A single intravenous infusion of gamma globulin as compared with four infusions in the treatment of acute Kawasaki syndrome. N Engl J Med 1991;324:1633-9.
7. Kobayashi T, Saji T, Otani T, et al. Efficacy of immunoglobulin plus prednisolone for prevention of coronary artery abnormalities in severe Kawasaki disease (RAISE study): A randomised, open-label, blinded-endpoints trial. Lancet 2012;379:1613-20.
8. Tremoulet AH, Best BM, Song S, et al. Resistance to intravenous immunoglobulin in children with Kawasaki disease. J Pediatr 2008;153:117-21.
9. Ishii M, Ueno T, Ikeda H, et al. Sequential follow-up results of catheter intervention for coronary artery lesions after Kawasaki disease: Quantitative coronary artery angiography and intravascular ultrasound imaging study. Circulation 2002;105:3004-10.
10. Onouchi Y, Gunji T, Burns JC, et al. ITPKC functional polymorphism associated with Kawasaki disease susceptibility and formation of coronary artery aneurysms. Nat Genet 2008;40:35-42.
11. Onouchi Y, Ozaki K, Buns JC, et al. Common variants in CASP3 confer susceptibility to Kawasaki disease. Hum Mol Genet 2010;19:2898-906.
12. Onouchi Y, Suzuki Y, Suzuki H, et al. ITPKC and CASP3 polymorphisms and risks for IVIG unresponsiveness and coronary artery lesion formation in Kawasaki disease. Pharmacogenomics J 2013;13:52-9.
13. Suzuki H, Terai M, Hamada H, et al. Cyclosporin A treatment for Kawasaki disease refractory to initial and additional intravenous immunoglobulin. Pediatr Infect Dis J 2011;30:871-6.
14. Ayusawa M, Sonobe T, Uemura S, et al. Revision of diagnostic guidelines for Kawasaki disease (the 5th revised edition). Pediatr Int 2005;47:232-4.
15. Kobayashi T, Inoue Y, Takeuchi K, et al. Prediction of intravenous immunoglobulin unresponsiveness in patients with Kawasaki disease. Circulation 2006;113:2606-12.
16. Taves D. Minimization: A new method of assigning patients to treatment and control groups. Clin Pharmacol Ther 1974;15: 443-53.
17. Pocock SJ, Simon R. Sequential treatment assignment with balancing for prognopstic factors in the controlled clinical trial. Biometrics 1975;31:103-15.
18. Research Committee on Kawasaki Disease. Report of subcommittee on standardization of diagnostic criteria and reporting of coronary artery lesions in Kawasaki disease. Tokyo, Japan: Ministry of Health and Welfare, 1984 (in Japanese).
19. Agresti A. Categorical data analysis. 3rd edn. Wiley, 2012.
20. Uehara R, Belay ED, Maddox RA, et al. Analysis of potential risk factors associated with nonresponse to initial intravenous immunoglobulin treatment among Kawasaki disease patients in Japan. Pediatr Infect Dis J 2008;27:155-60.
21. Durongpisitkul K, Soongswang J, Laohaprasitiporn D, et al. Immunoglobulin failure and retreatment in Kawasaki disease. Pediatr Cardiol 2003;24:145-8.
22. Burns JC, Capparelli EV, Brown JA, et al. Intravenous gammaglobulin treatment and retreatment in Kawasaki disease. US/Canadian Kawasaki Syndrome Study Group. Pediatr Infect Dis J 1998;17:1144-8.
23. Hashino K, Ishii M, Iemura M, et al. Re-treatment for immune globulin-resistant Kawasaki disease: A comparative study of additional immune globulin and steroid pulse therapy. Pediatr Int 2001;43:211-17.
24. Moffett BS, Syblik D, Denfield S, et al. Epidemiology of immunoglobulin resistant Kawasaki disease: Results from a large, national database. Pediatr Cardiol 2015;36:374-8.
25. Kanai T, Ishiwata T, Kobayashi T, et al. Ulinastatin, a urinary trypsin inhibitor, for the initial treatment of patients with Kawasaki disease: A retrospective study. Circulation 2011;124:2822-8.
26. Burns JC, Wiggins JW Jr, Toews WH, et al. Clinical spectrum of Kawasaki disease in infants younger than 6 months of age. J Pediatr 1986;109:759-63.
27. Chang FY, Hwang B, Chen SJ, et al. Characteristics of Kawasaki disease in infants younger than six months of age. Pediatr Infect Dis J 2006;25:241-4.
28. Yanagawa H, Nakamura Y, Yashiro M, et al. Results of the nationwide epidemiologic survey of Kawasaki disease in 1995 and 1996 in Japan. Pediatrics 1998;102:E65.
29. Park YW, Han JW, Park IS, et al. Epidemiologic study of Kawasaki disease in 6 months old and younger infants. Korean J Pediatr 2008;51:1320-3.
30. Tsuchida S, Yamanaka T, Tsuchida R, et al. Epidemiology of infant Kawasaki disease with a report of the youngest neonatal case ever reported in Japan. Acta Paediatr 1996;85: 995-7.
31. Lee EJ, Park YW, Hong YM, et al. Epidemiology of Kawasaki disease in infants 3 months of age and younger. Korean J Pediatr. 2012;55:202-5.
32. Newburger JW, Takahashi M, Gerber MA, et al. Diagnosis, treatment, and long-term management of Kawasaki disease: A statement for health professionals from the committee on rheumatic fever, endocarditis and Kawasaki disease, council on cardiovascular disease in the young, American Heart Association. Circulation 2004;110:2747-71.
33. Scott JS, Ettedgui JA, Naches WH. Cost-effective use of echocardiography in children with Kawasaki disease. Pediatrics 1999;104:e5.
34. McMorrow Tuohy AM, Tani LY, Cetta F, et al. How many echocardiograms are necessary for follow-up evaluation of patients with Kawasaki disease? Am J Cardiol 2001;88:328-30.
35. Tremoulet AH, Jain S, Jaggi P, et al. Infliximab for intensification of primary therapy for Kawasaki disease: A phase 3 randomised, double-blind, placebo-controlled trial. Lancet 2014;383:1731-8.
36. Newburger JW, Sleeper LA, McCrindle BW, et al. Randormized trial of pulsed corticosteroid therapy for primary treatment of Kawasaki disease. New Engl J Med 2007;356:663-75.