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Development of PK/PD Model for Individualized Propofol Dosing

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00948597
Recruitment Status : Completed
First Posted : July 29, 2009
Last Update Posted : January 9, 2014
Information provided by (Responsible Party):
Children's Hospital Medical Center, Cincinnati

Brief Summary:

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 []. 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 or disease
Obesity Elective Surgery

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Study Type : Observational
Actual Enrollment : 26 participants
Observational Model: Case-Only
Time Perspective: Prospective
Official Title: A Non-Interventional Study to Develop a Pharmacokinetic - Pharmacodynamic Model for Individualized Propofol Dosing
Study Start Date : July 2009
Actual Primary Completion Date : July 2012
Actual Study Completion Date : December 2013

Resource links provided by the National Library of Medicine

Drug Information available for: Propofol

Primary Outcome Measures :
  1. 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 ]

Secondary Outcome Measures :
  1. Population PK/PD model (NON-MEM) using patient demographic and clinical data. [ Time Frame: one year ]

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.

Information from the National Library of Medicine

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, Learn About Clinical Studies.

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Ages Eligible for Study:   5 Years to 18 Years   (Child, Adult)
Sexes Eligible for Study:   All
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00948597

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United States, Ohio
Cincinnati Children's Hospital Medical Center
Cincinnati, Ohio, United States, 45229
Sponsors and Collaborators
Children's Hospital Medical Center, Cincinnati
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Principal Investigator: Alexander A Vinks, PharmD, PhD Children's Hospital Medical Center, Cincinnati
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Children's Hospital Medical Center, Cincinnati Identifier: NCT00948597    
Other Study ID Numbers: 2009-0721
First Posted: July 29, 2009    Key Record Dates
Last Update Posted: January 9, 2014
Last Verified: January 2014
Keywords provided by Children's Hospital Medical Center, Cincinnati:
elective surgical procedure
Obese subjects