Hypothermia's Impact on Pharmacology (HIP)
Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
연구 개요
상세 설명
Background:
Therapeutic hypothermia is used in the pediatric intensive care unit, and is being studied in the setting of pediatric cardiac arrest. Following cardiac arrest, multiple organ dysfunction syndrome, especially renal and hepatic dysfunction, is common and affects the metabolism and excretion of drugs. In addition, very little is known about the impact of hypothermia on a child's ability to metabolize medications. Dose adjustments may be required in the setting of hypothermia to avoid under-dosing and over-dosing of medications. Improper dosing and drug accumulation of sedatives and opiates can worsen existing neurologic, circulatory and respiratory failure. The measurement of the actual drug and metabolite concentrations in the body (pharmacokinetics) provides information on how a child metabolizes medications. In addition, variability in these concentrations after the administration of equal doses to different children may result from genetically driven differences in drug metabolizing systems (pharmacogenetics). Finally, these genetic differences may respond differently to hypothermia. Our overarching hypothesis is that morphine and midazolam disposition will be affected by temperature management even when accounting for potentially confounding quantifiable factors of organ dysfunction and genetic differences.
Objectives:
The objectives of this study, Hypothermia's Impact on Pharmacology 2, are
- To estimate the impact of hypothermia on the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest and
- To estimate the impact of genetic factors on the variability in morphine and midazolam pharmacokinetics, specifically in the setting of hypothermia.
Sophisticated modeling and simulation techniques will be utilized to examine the highly dynamic changes in physiology associated with critical illness, drug disposition, pharmacogenetics and temperature modulation. The models created using this approach will be implemented to optimize the prospective treatment of these critically ill children.
Study Design:
Prospective pharmacokinetic study
연구 유형
등록 (실제)
연락처 및 위치
연구 장소
-
-
Alabama
-
Birmingham, Alabama, 미국, 35294
- University of Alabama at Birmingham
-
-
District of Columbia
-
Washington, District of Columbia, 미국, 20010
- Children's National Medical Center
-
-
Kentucky
-
Louisville, Kentucky, 미국, 40202
- University of Louisville
-
-
Michigan
-
Ann Arbor, Michigan, 미국, 48109
- Univeristy of Michigan
-
-
Ohio
-
Columbus, Ohio, 미국, 43205
- Nationwide Children's Medical Center
-
-
Pennsylvania
-
Hershey, Pennsylvania, 미국, 19104
- Pennsylvania State University Hersey Medical Center
-
Philadelphia, Pennsylvania, 미국, 19104
- The Children's Hospital of Philadelphia
-
Pittsburgh, Pennsylvania, 미국, 15224
- University of Pittsburgh
-
-
Washington
-
Seattle, Washington, 미국, 98105
- Seattle Children's Hospital
-
-
참여기준
자격 기준
공부할 수 있는 나이
건강한 자원 봉사자를 받아들입니다
연구 대상 성별
샘플링 방법
연구 인구
설명
Inclusion Criteria:
- Be greater than or equal to three (3) kg
- Receiving or have received morphine and/or midazolam as part of clinical care
- Receiving hypothermia after any cardiac arrest
- Provide Informed Consent
Exclusion Criteria:
- Receiving renal replacement therapy [example Continuous Veno-Venous Hemofiltration (CVVH), Continuous Veno-Venous Hemodialysis (CVVHD), and Continuous Veno-Venous Hemodiafiltration (CVVHDF)]
- Receiving plasmapheresis
공부 계획
연구는 어떻게 설계됩니까?
디자인 세부사항
코호트 및 개입
그룹/코호트 |
|---|
|
Pediatric after Cardiac Arrest
Pediatric patients greater than 3 kg.
and less than 18 years suffering cardiac arrest who have been given or currently receiving morphine and/or midazolam and receiving hypothermia.
|
연구는 무엇을 측정합니까?
주요 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
기간: 2.5 years
|
The objective of this aim is to identify the physiologic manifestations of cardiac arrest and MODS that underlie the variability in morphine and midazolam pharmacokinetics.
|
2.5 years
|
2차 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Impact of genetic factors
기간: 2.5 years
|
The objective of this aim is to estimate the impact of genetic factors that underlie the variability in morphine and midazolam pharmacokinetics (PK), specifically in the setting of pediatric cardiac arrest.
In this aim we will investigate the effect of genotype on pharmacokinetic parameters for morphine and midazolam.
|
2.5 years
|
기타 결과 측정
결과 측정 |
측정값 설명 |
기간 |
|---|---|---|
|
Manifestations of hypothermia
기간: 2.5 years
|
The objective of this aim is to identify the manifestations of hypothermia that underlie the variability in morphine and midazolam pharmacokinetics in children after cardiac arrest.
In this aim we will investigate the effect of body temperature on PK parameters for morphine and midazolam.
|
2.5 years
|
공동 작업자 및 조사자
수사관
- 수석 연구원: Athena F Zuppa, MD MSCE, Children's Hospital of Philadelphia
연구 기록 날짜
연구 주요 날짜
연구 시작 (실제)
기본 완료 (실제)
연구 완료 (실제)
연구 등록 날짜
최초 제출
QC 기준을 충족하는 최초 제출
처음 게시됨 (추정)
연구 기록 업데이트
마지막 업데이트 게시됨 (실제)
QC 기준을 충족하는 마지막 업데이트 제출
마지막으로 확인됨
추가 정보
이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .