Nicardipine Hydrochloride Injectable Phase IV Clinical Trial-Study on the antihypertensive effect and safely of nicardipine for acute aortic dissection

급성대동맥해리에 대한 혈압강하요법으로서의 Nicardipine.HCI 주사액(Perdipine$^{circledR}$)의 유효성 및 안전성을 검토하기 위한 다기관 공동, 공개 제4상 임상시험

  • Kim, Kyung-Hwan (Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Hospital) ;
  • Moon, In-Sung (Department of Surgery, College of Medicine The Catholic University of Korea, Kang-Nam St, Mary's Hospital) ;
  • Park, Jang-Sang (Department of Surgery, College of Medicine The Catholic University of Korea, Kang-Nam St, Mary's Hospital) ;
  • Koh, Yong-Bok (Department of Surgery, College of Medicine The Catholic University of Korea, Kang-Nam St, Mary's Hospital) ;
  • Ahn, Hyuk (Department of Thoracic and Cardiovascular Surgery, Seoul National University College of Medicine, Seoul National University Hospital)
  • 김경환 (서울대학교 의과대학 흉부외과학교실, 서울대학교병원 임상의학연구소) ;
  • 문인성 (가톨릭대학교 의과대학 외과학교실 강남성모병원 외과) ;
  • 박장상 (가톨릭대학교 의과대학 외과학교실 강남성모병원 외과) ;
  • 고용복 (가톨릭대학교 의과대학 외과학교실 강남성모병원 외과) ;
  • 안혁 (서울대학교 의과대학 흉부외과학교실, 서울대학교병원 임상의학연구소)
  • Published : 2002.04.01

Abstract

Background: We performed a phase IV clinical trial to examine the usefulness of a continuous infusion of nicardipine hydrochloride to control hypertension in patients with acute aortic dissection. material and Method: Systolic/diastolic blood pressure, and heart rate were monitored before and after the intravenous administration of nicardipine in 31 patients with aortic diseases. The period of nicardipine administration in each patient was from 3 to 14 days. Efficacy was evaluated by determining the average amount of blood pressure reduction on the 3rd day of drug administration. The dosage of another antihypertensive agent was slowly tapered down, and ultimately replaced by the test drug. Result: 28 patients were diagnosed as acute aortic dissection, 2 patients as rupture of the aortic arch aneurysm, and 1 patient as traumatic aortic rupture. Mean age was 53.9 $\pm$ 14.9(29~89) years, and 21 patients(67.7%) were male. 14 patients(32.3%) had complications associated with underlying aortic disease: aortic insufficiency in 7, hemopericardium in 6, acute renal failure in 1, paraplegia in 1, lower extremity ischemia in 1, and hemothorax in 1. The time needed to reach the target blood pressure was within 15 minutes in 16, from 15 to 30 minutes in 10, from 30 to 45 minutes in 3 and from 45 to 60 minutes in 2, and their baseline average systolic, diastolic, and mean arterial blood pressures(mmHg) were 147$\pm$23, 82.3$\pm$ 18.6, and 104 $\pm$ 18, respectively. Average systolic, diastolic, and mean arterial blood pressures(mmHg) on the third day of nicardipine infusion were 119$\pm$ 12, 69$\pm$9, and 86$\pm$8, and they all showed statistically significant decrease(p<0.05). The average systolic, diastolic, and mean arterial blood pressure(mmHg) after the discontinuation of the nicardipine infusion were 119 $\pm$ 15, 71 $\pm$ 14, and 86$\pm$ 13, respectively. No significant difference was observed between the average pressures measured on the third day and those measured after the discontinuation of the nicardipine infusion, and no definite side effects were observed during the study period. Conclusion: Nicardipine hydrochloride was both effective and safe at controlling blood pressure in patients with acute aortic dissection.

배경: 저자들은 한국인에 있어서의 급성대동맥박리에 대한 nicardipine의 혈압강하요법에 대한 임상적 유용성을 검토하고자 국내 제4상 임상시험을 실시하였다. 대상 및 방법: 31명의 대동맥 질환 환자에서 시험약의 투여 전후의 수축기 및 이완기 혈압, 심박수 등을 시간변화에 따라 비교 관찰하였다. 시험약식 투여기간은 원칙적으로 3일 이상 14일 이하로 하였으며, 투여 3일째의 평균혈압강하도를 평가하였다. 시험약 사용전 다른 강압제를 사용하고 있었던 경우는 기존 사용약제의 용량을 줄이면서 시험약으로 대체하여 결국 기존 사용약제를 사용하지 않는 것을 원칙으로 하였다. 결과: 연구의 대상이 된 환자는 급성 대동맥 박리가 28명, 대동맥궁류 파열이 2명, 외상성 대동맥 파열이 1명이었다. 연령은 53.9$\pm$14.9(29~89)세였고, 남자가 21명 (67.7%)이었다. 대동맥질환에 기인한 합병증은 대동맥판 폐쇄부전이 7례, 혈성심낭 6례, 급성 신부전 1례, 하지마비 1례, 하지허혈 1례 등이었다. 목표혈압 도달은 15분이내가 16례로 가장 많았고, 15분이상 30분이내가 10명, 30분이상 45분이내가 3명, 45분이상 60분 이내에 도달한 경우가 2명이었다. 관찰기 혈압은 수축기혈압, 이완기혈안, 평균혈압이 각각 147$\pm$23mmHg, 82.3$\pm$18.6mmHg, 104$\pm$18mmHg이었고, 3일째 측정하였을 때 119$\pm$12mrnHg, 69$\pm$grnmHg, 86$\pm$BmmHg로 의미있게 감소하였음을 확인하였다. Nicardipine 투여 종료 시에측정한 수축기 혈압, 이완기혈압, 평균혈압은 각각 119$\pm$ 15mmHg, 70$\pm$ 14mmHg, 86$\pm$ 13mmHg로 3일째 측정한 혈압과 비교하였을 때 의미있는 상승 혹은 하강현상은 관찰되지 않았고 비교적 혈압 하강 상태가 잘 유지되고 있음을 알 수 있었다. 지속적 정맥 투여 중 부작용은 뚜렷하게 관찰할 수 없었다. 결론: 대동맥 박리에 동반된 고혈압에서 nicardipine을 사용하여 만족할만한 혈압하강 효과를 얻었으며, 뚜렷한 부작용이 없이 안전하게 사용할 수 있다는 결론을 내렸다.

Keywords

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