Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients

Obese Clinical Trial

— POP-II  

Official title:

Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01097148
• Other study ID #: V.09.231/R-09
• Status: Completed
• Phase: Phase 4
• First received: March 31, 2010
• Last updated: October 12, 2010
• Start date: November 2009
• Est. completion date: April 2010

Study information

• Verified date: November 2009
• Source: St. Antonius Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Interventional

Clinical Trial Summary

Rationale: Obesity is an increasing health risk worldwide, with the USA recording prevalence in adults of around 20%. The mean body weight of obese patients is also increasing. One of the strategies to treat extreme obesity (Body Mass Index (BMI) > 40 kg/m2) is weight-reducing surgery like laparoscopic gastric banding or gastric bypass. During anaesthesia, morbidly obese patients are exposed to an increased risk at developing postoperative wound infections, apnoea and thrombotic events and may be more difficult to intubate. Routinely, amongst others, cefazolin, morphine, nadroparin and atracurium are administered in standard dosages. However, it is not known to what extend the pharmacokinetics and/or -dynamics of these drugs are affected in morbidly obese patients. Therefore, evidence-based dosing schedules for these drugs in morbidly obese patients should be developed.

Objective: The study is performed in order to develop population pharmacokinetic and/or pharmacodynamic models of the routinely used drug therapies during bariatric surgery in morbidly obese patients (BMI > 40 kg/m2): cefazolin, morphine, nadroparin and atracurium.

A covariate analysis will be performed in order to account for variability in pharmacokinetic and/or pharmacodynamic parameters. This covariate analysis will take into account procedure and patient bound covariates, with specific interest for body weight as a covariate. Whenever possible, non-obese patients will be included in the covariate analysis.

The results will be used to develop individualised dosing schemes for routinely used drugs peri-operatively in morbidly obese patients.

Study design: A randomised, prospective, observational, therapeutic and invasive study.

Study population: Morbidly obese patients with a Body Mass Index > 40 kg/m2 undergoing laparoscopic banding or gastric bypass surgery, 18-60 years old. A total of 20 patients will be included in the study.

Intervention (if applicable): All measurements and data collection will take place around administration of drugs that are given according to routine clinical practice (cefazolin 2 grams for prophylaxis of infections, morphine 10 mg intravenously at the end of surgery, a patient-controlled analgesia (PCA) pump with morphine for postoperative pain relief and nadroparin 0,6 ml for trombo-embolic prophylaxis). For muscle relaxation, patients are randomised to receive one of two generally accepted dosing regimen of atracurium (0.5 mg/kg based on ideal body weight or 0.5 mg/kg based on total body weight). Peri- and postoperatively, a maximum amount of 70 ml of blood will be collected from an indwelling arterial line for measurement of concentrations of cefazolin, morphine, and anti-Xa (nadroparin). One week after surgery the patient will be checked for thrombosis using ultrasonography.

Main study parameters/endpoints:

Primary endpoints to evaluate in morbidly obese patients are;

• pharmacokinetic parameters of cefazolin in blood;

• pharmacokinetic parameters of morphine and metabolites in blood;

• time course of anti-factor Xa levels in blood following nadroparin;

• time course of the pharmacodynamic effect of atracurium.

Secondary endpoints to evaluate in morbidly obese patients are:

• to compare primary endpoints (obtained in morbidly obese patients) with data of non-obese patients

• the occurrence of postoperative wound infections;

• postoperative pain scores, sedation scores and nausea scores;

• the occurrence of bleedings or thrombotic events ;

• required amounts of morphine (PCA);

• to compare the time course of the pharmacodynamic effect of two different doses of atracurium.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• Morbidly obese patients undergoing bariatric surgery with a BMI > 40 kg/m2, ASA I-III

Exclusion Criteria:

• Epilepsy, pregnancy, breastfeeding and known allergy allergies to cefazolin, morphine, nadroparin, atracurium, or benzene sulphonic acid. History of coagulation disorder or history of heparin/LMWH induced thrombocytopenia.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacodynamics Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Diagnostic

Related Conditions & MeSH terms

• Atracurium
• Cefazolin
• Morphine
• Nadroparin
• Obese

Intervention

Drug:
• Atracurium, TBW
Dose atracurium 0.5 mg/kg based on total body weight

Locations

Country	Name	City	State
Netherlands	St. Antonius Hospital	NIeuwegein

Sponsors (1)

Lead Sponsor	Collaborator
St. Antonius Hospital

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time course of the pharmacodynamic effect of atracurium		6 months	No
Primary	Pharmacokinetic parameters of cefazolin in blood		6 months	No
Primary	Pharmacokinetic parameters of morphine and metabolites in blood		6 months	No
Primary	Time course of anti-factor Xa levels in blood following nadroparin		6 months	No
Secondary	Dosing of atracurium based on total or ideal body weight		6 months	No
Secondary	To compare primary endpoints (obtained in morbidly obese patients) with data of non-obese patients		6 months	No
Secondary	The occurrence of postoperative wound infections		6 months	No
Secondary	Postoperative pain scores, sedation scores and nausea scores		6 months	No
Secondary	The occurrence of bleedings or thrombotic events		6 months	No
Secondary	Required amounts of morphine (PCA)		6 months	No