Cardiac ArrestHIPNCT01560338
Hypothermia's Impact on Pharmacology
An observational study of Cardiac Arrest and Hypothermia, run by Children's Hospital of Philadelphia at 9 sites in United States.
Trial summary
The purpose of the study will help us understand the complex interaction between hypothermia (cooling) and pharmacogenetics (how specific genes effect how drugs are handled), and their impact on how routinely given sedation drug are broken down and used by the body when given to children after cardiac arrest (when… Read more about this study
- Who is it for?
- Ages Up to 18 years
- Conditions the study is for
- Cardiac Arrest, Hypothermia
- How many people
- 41 participants
- Where
- 9 sitesUnited States
- Study dates
- Mar 2012to 28 Jan 2018
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Study population: The study population is the pediatric population equal to or greater than 3 kg and less than 18 years of age AND have had or currently receiving morphine and/or midazolam AND receive hypothermia after cardiac arrest administered as part of clinical care.
Who may be able to join
- 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
Who cannot join
- Receiving renal replacement therapy [example Continuous Veno-Venous Hemofiltration (CVVH), Continuous Veno-Venous Hemodialysis (CVVHD), and Continuous Veno-Venous Hemodiafiltration (CVVHDF)]
- Receiving plasmapheresis
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Univeristy of Michigan
Ann Arbor, Michigan, 48109
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Nationwide Children's Medical Center
Columbus, Ohio, 43205
Pennsylvania State University Hersey Medical Center
Hershey, Pennsylvania, 19104
University of Louisville
Louisville, Kentucky, 40202
The Children's Hospital of Philadelphia
Philadelphia, Pennsylvania, 19104
University of Pittsburgh
Pittsburgh, Pennsylvania, 15224
Seattle Children's Hospital
Seattle, Washington, 98105
Children's National Medical Center
Washington D.C., District of Columbia, 20010
About this study
Official title: Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
The purpose of the study will help us understand the complex interaction between hypothermia (cooling) and pharmacogenetics (how specific genes effect how drugs are handled), and their impact on how routinely given sedation drug are broken down and used by the body when given to children after cardiac arrest (when heart stops pumping blood) and are critically ill.
Read the detailed description
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
- Conditions
- Cardiac Arrest, Hypothermia
- Keywords
- Pharmacokinetics, Midazolam, Morphine, Cardiac Arrest, Hypothermia
- Medical subject headings
- Heart Arrest, Hypothermia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
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.
Measured: 2.5 years
Secondary outcomes (1)
Impact of genetic factors
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.
Measured: 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Mar 2012 (estimated)
- Study startMar 2012
- Primary completionJan 2018
- Study completion28 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiac ArrestStudies of the same condition, open and under way.
- More trials run by Children's Hospital of PhiladelphiaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Children's Hospital of Philadelphia
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Athena F Zuppa, MD MSCE, Principal investigator, Children's Hospital of Philadelphia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01560338
- Sponsor's protocol ID
- 12-009214
- Other IDs
- RO1HL11274501A1
- Acronym
- HIP
- Status last verified
- Mar 2021
- First submitted
- 20 Mar 2012
- Last updated
- 2 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 2 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Hypothermia on Midazolam and Morphine Pharmacokinetics
- ClinicalTrials.gov ID
- NCT01560338
- Acronym / sponsor ID
- HIP / 12-009214
- Conditions
- Cardiac Arrest, Hypothermia
- Keywords
- Pharmacokinetics, Midazolam, Morphine, Cardiac Arrest, Hypothermia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 41 participants (actual)
- Lead sponsor
- Children's Hospital of PhiladelphiaUniversity, hospital or other
- Study start
- Mar 2012 (actual)
- Primary completion
- Jan 2018 (actual)
- Study completion
- 28 Jan 2018 (actual)
- First posted
- 22 Mar 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of the study will help us understand the complex interaction between hypothermia (cooling) and pharmacogenetics (how specific genes effect how drugs are handled), and their impact on how routinely given sedation drug are broken down and used by the body when given to children after cardiac arrest (when heart stops pumping blood) and are critically ill.
Detailed description
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
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- Up to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
- Study population
- The study population is the pediatric population equal to or greater than 3 kg and less than 18 years of age AND have had or currently receiving morphine and/or midazolam AND receive hypothermia after cardiac arrest administered as part of clinical care.
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (2 listed)
- Receiving renal replacement therapy [example Continuous Veno-Venous Hemofiltration (CVVH), Continuous Veno-Venous Hemodialysis (CVVHD), and Continuous Veno-Venous Hemodiafiltration (CVVHDF)]
- Receiving plasmapheresis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam
Time frame: 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.
1 secondary outcome
Impact of genetic factors
Time frame: 2.5 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Mar 2021.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Athena F Zuppa, MD MSCE principal investigator
Children's Hospital of Philadelphia
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiac Arrest and Hypothermia, run by Children's Hospital of Philadelphia at 9 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Mar 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Physiologic manifestations of cardiac arrest and Multiple Organ Dysfunction Syndrome (MODS) in relation to morphine and midazolam (time frame: 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Mar 2021.