부당 경량아(Small for Gestational Age)로 태어난 사춘기 이전의 저신장 소아에서 6개월간 인성장호르몬(EutropinTM Inj.) 치료의 유효성과 안전성에 대한 단일군 대상, 제3상 임상시험 연구
A Single-Arm, Phase III Study to Assess Efficacy and Safety after 6-Month-Treatment of EutropinTM Inj. (Recombinant Human Growth Hormone) in Prepubertal Children with Short Stature due to Small for Gestational Age
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목 적:본 연구는 단일군, 다기관, 제3상 국내 임상시험으로, 부당경량아(small for gestational age)로 태어난 저신장 환아에서 인성장호르몬인 EutropinTM Inj. 치료의 유효성 및 안전성을 평가하고자 수행하였다. 방 법:2005년부터 2007년까지 부당경량아로 태어난 사춘기 이전 저신장 환아를 대상으로 하였다. EutropinTM Inj.을 0.48 mg/kg/wk 용량으로 6개월간 투여하였다. 일차 목표로 시작 시와 6개월 째 성장속도의 차이를 측정하였으며, 또한, 다양한 변수를 확인하여 이차 목표 및 안정성 평가를 살펴보았다. 결 과:EutropinTM Inj. 투여 전 성장속도 5.36±1.59 cm/yr에서 6개월째 10.66±2.03 cm/yr으로 통계적으로 유의하게 증가하였다(P ˂0.0001). 이차 유효성 평가변수인 3개월째 성장속도, 역연령에 대한 신장표준편차지수, 체중표준편차지수, 골성숙도 및 IGF-I, IGFBP-3 모두 통계적으로 유의하게 증가되었다. 임상적으로 유의한 이상반응이나, 혈액 검사치의 이상은 관찰되지 않았다. 결 론:부당경량아로 태어나 따라잡기성장이 일어나지 않은 저신장 환아들을 대상으로 성장호르몬(EutropinTM Inj.)을 6개월간 투여하여 성장개선의 유효성과 안전성을 확인할 수 있었으며 앞으로 보다 장기적인 치료기간의 연구가 필요하겠다.
Abstract
Purpose:Recombinant human growth hormone is an effective therapy for short-statured children born small for their gestational age (SGA). This single-arm, multicenter, phase III clinical study of such children was designed to assess the efficacy and safety of treating them with recombinant human-growth-hormone (EutropinTM Inj.) for 6 months. Methods:Between 2005 and 2007, 30 treatment naive, prepubertal, short-statured SGA-born children were recruited as participants. EutropinTM Inj. was administered for 6 months with a subcutaneous dose of 0.48 mg/kg/ wk. The primary endpoint was the change in height velocity from the baseline to month 6. Various parameters were checked to obtain secondary outcome measures and to meet safety criteria. Results:Height velocity significantly increased from 5.36±1.59 cm/yr at baseline to 10.66±2.03 cm/yr at month 6 (P ˂0.0001). Secondary outcome measures (height velocity at month 3, height SDS for chronological age (CA), weight SDS for CA, bone maturation, and IGF-I and IGFBP-3 levels) were also significantly increased. EutropinTM Inj. was well tolerated and safe over 6 months of treatment. Conclusion:The clinical efficacy and safety of EutropinTM Inj. was demonstrated for the 6 month treatment of prepubertal children with short stature due to SGA. Further long-term study is needed.
참고문헌 (19)
- Bercu BB, "Growth hormone: relevance to pediatrics, In Human growth hormone: research and clinical practice" (2000), Humana press
- Hindmarsh PC, "Current indications for growth hormone therapy. Preface", Endocr Dev, 18, pp.8~ (2010)
- Wollmann HA, "Intrauterine growth restriction: definition and etiology", Horm Res, 49(2), pp.1~6 (1998)
- Fjellestad-Paulsen A, "Three-year data from a comparative study with recombinant human growth hormone in the treatment of short stature in young children with intrauterine growth retardation", Acta Paediatr, 87, pp.511~517 (1998)
- Liu Y, "Long-term consequences of early linear growth retardation (stunting) in Swedish children", Pediatr Res, 47, pp.475~480 (2000)
- Karlberg J, "Growth in full-term small- for-gestational-age infants: from birth to final height", Pediatr Res, 38, pp.733~739 (1995)
- 이기형, "약물요법", 저신장 소아의 성장호르몬 치료, 2008, pp.51(9), 849~855[DOI]
- Hong CE, "Textbook of pediatrics. 9th ed", pp.277~ (2007), Daehan Printing & Publishing Co., Ltd
- Tanner JM, "Clinical longitudinal standards for height, weight, height velocity, weight velocity, and stages of puberty", Arch Dis Child, 51, pp.170~179 (1976)
- Debouverie M, "Clinical follow-up of 304 patients with multiple sclerosis three years after mitoxantrone treatment", Mult Scler, 13, pp.626~631 (2007)
- Saenger P, "US experience in evaluation and diagnosis of GH therapy of intrauterine growth retardation", small-for-gestational-age children, 2002, pp.58(3), 27~29
- Wilson TA, "Update of guidelines for the use of growth hormone in children: the Lawson Wilkins Pediatric Endocrinology Society Drug and Therapeutics Committee", J Pediatr, 143, pp.415~421 (2003)
- Sas T, "Growth hormone treatment in children with short stature born small for gestational age: 5-year results of a randomized, double-blind, dose-response trial", J Clin Endocrinol Metab, 84, pp.3064~3070 (1999)
- Chatelain P, "Growth hormone therapy for short children born small for gestational age", Horm Res, 68, pp.300~309 (2007)
- Gharib H, "American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update", Endocr Pract, 9, pp.64~76 (2003)
- Arends NJ, "GH treatment and its effect on bone mineral density, bone maturation and growth in short children born small for gestational age: 3-year results of a randomized, controlled GH trial", Clin Endocrinol (Oxf), 59, pp.779~787 (2003)
- de Waal WJ, "Endogenous and stimulated GH secretion, urinary GH excretion, and plasma IGF-I and IGF-II levels in prepubertal children with short stature after intrauterine growth retardation. The Dutch Working Group on Growth Hormone", Clin Endocrinol (Oxf), 41, pp.621~630 (1994)
- Lee PA, "International Small for Gestational Age Advisory Board. International Small for Gestational Age Advisory Board consensus development conference statement: management of short children born small for gestational age, April 24-October 1, 2001", Pediatrics, 111, pp.1253~1261 (2003)
- Sas T, "Body composition, blood pressure, and lipid metabolism before and during long-term growth hormone (GH) treatment in children with short stature born small for gestational age either with or without GH deficiency", J Clin Endocrinol Metab, 85, pp.3786~3792 (2000)