Development of PK/PD Model for Individualized Propofol Dosing

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier:
NCT00948597
First received: July 27, 2009
Last updated: January 8, 2014
Last verified: January 2014
  Purpose

The U.S. National Health and Nutrition Examination Survey of 1994 indicated that 59% of American men and 49% of women have body mass indexes (BMIs) over 25. Extreme obesity, defined as a BMI of 40 or more, was found in 2% of the men and 4% of the women [http://www.cdc.gov/nchs/nhanes.htm]. The newest survey in 2007 indicates an alarming increase in BMI; 63% of Americans are overweight, with 26% now in the obese category. With extreme obesity as high as 26-30% in adults, obesity percentages in children are also sharply on the rise. These alarming numbers pose a major clinical problem in terms of the safe and effective use of drugs in children.

Obesity may alter the disposition and/or clearance of drugs in the body as well as the response, which should be considered when using anesthetics in these patients. Total intravenous anesthesia (TIVA) with propofol is widely used in children, adolescents and adults undergoing surgery, because of rapid onset of action, ease of titration and rapid offset of action. While extensive research on optimal propofol dosing has been performed in non-obese adults, including in critically ill mechanically ventilated adult patients by the investigators' collaborators, there is no evidence on required dosages in morbidly obese adult or pediatric patients of this highly lipophilic agent. As a consequence, serious problems do arise due to under- and overdosing, increasing the risk of inadequate effects and adverse events, respectively. Crucial additional information is needed on the pharmacokinetics of drugs used in morbidly obese children to improve safety and efficacy.

This proposal will test a novel approach by identifying pharmacokinetic/pharmacodynamic (PK/PD) factors that are associated with response to therapy and adverse events. If successful, this study will provide proof of concept data for PK/PD model-based dosing strategy that can be implemented into daily clinical care to allow tailoring of dose to individual needs. Propofol is a versatile anesthetic agent which if dosed to individual needs based on a patient's characteristics and specific PK/PD parameters, will allow individualized dosing, thereby greatly reducing related toxicities. The prospective identification of predictive factors in these morbidly obese high-risk patients represents a new approach to an increasingly common clinical problem. The investigators expect that this study will generate the PK/PD data necessary to continue with a well powered prospective clinical trial.


Condition
Obesity
Elective Surgery

Study Type: Observational
Study Design: Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Non-Interventional Study to Develop a Pharmacokinetic - Pharmacodynamic Model for Individualized Propofol Dosing

Resource links provided by NLM:


Further study details as provided by Children's Hospital Medical Center, Cincinnati:

Primary Outcome Measures:
  • Change in propofol clearance and volume of distribution (for determination of effective concentration); Depth of anesthesia. [ Time Frame: Samples will be analyzed within one month of collection ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Population PK/PD model (NON-MEM) using patient demographic and clinical data. [ Time Frame: one year ] [ Designated as safety issue: Yes ]

Biospecimen Retention:   Samples With DNA

Participation involves the collection of one blood sample (3.0 ml) in an EDTA (lavender top) tube for pharmacogenetic testing. Genomic DNA will be extracted using standard procedures. Participation in pharmacogenetic testing is optional and requires additional consent; subjects who refuse pharmacogenetifc testing may still be enrolled in this study.


Enrollment: 26
Study Start Date: July 2009
Study Completion Date: December 2013
Primary Completion Date: July 2012 (Final data collection date for primary outcome measure)
  Show Detailed Description

  Eligibility

Ages Eligible for Study:   5 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Patients will be recruited from the Cincinnati Children's Hospital Medical Center Surgical Weight Loss Program for Teens (Thomas Inge, Director), supplemented with general surgery patients who are overweight and have a Body Mass Index (BMI) of more than 30.

Criteria

Inclusion Criteria:

  • Age 5 to 18 years of age;
  • Have a Body Mass Index (BMI) greater than 30;
  • Be scheduled for bariatric or other elective surgical procedure;
  • Will be administered propofol anesthesia as part of procedure and standard of care and subject is expected to be under anesthesia for at least 60 minutes;
  • Signed and dated IRB-approved Informed Consent or Parental Permission and Assent form, as applicable.

Exclusion Criteria:

  • Patients receiving investigational agent as part of another clinical study;
  • Patients with severe developmental delay, known neurological disorders;
  • Conditions where the placement of the sensor or process of assessment could interfere with the BIS monitoring;
  • Allergy to propofol / anaphylaxis to egg protein;
  • History of severe sleep apnea;
  • Anticipated difficult airway access;
  • Significant allergies and sensitivities to tape and/or adhesives.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00948597

Locations
United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
Investigators
Principal Investigator: Alexander A Vinks, PharmD, PhD Children's Hospital Medical Center, Cincinnati
  More Information

No publications provided by Children's Hospital Medical Center, Cincinnati

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Children's Hospital Medical Center, Cincinnati
ClinicalTrials.gov Identifier: NCT00948597     History of Changes
Other Study ID Numbers: 2009-0721
Study First Received: July 27, 2009
Last Updated: January 8, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Children's Hospital Medical Center, Cincinnati:
propofol
elective surgical procedure
Obese subjects

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Propofol
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Hypnotics and Sedatives

ClinicalTrials.gov processed this record on July 26, 2014