Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients (POP-II)

This study has been completed.
Sponsor:
Information provided by:
St. Antonius Hospital
ClinicalTrials.gov Identifier:
NCT01097148
First received: March 31, 2010
Last updated: October 12, 2010
Last verified: November 2009
  Purpose

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.

Condition Intervention Phase
Obese
Atracurium
Cefazolin
Morphine
Nadroparin
Drug: Atracurium, TBW
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Pharmacodynamics Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Diagnostic
Official Title: Peri -and Postoperative Drug Therapy Schedules for Morbidly Obese Patients

Resource links provided by NLM:


Further study details as provided by St. Antonius Hospital:

Primary Outcome Measures:
  • Time course of the pharmacodynamic effect of atracurium [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of cefazolin in blood [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Pharmacokinetic parameters of morphine and metabolites in blood [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Time course of anti-factor Xa levels in blood following nadroparin [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Dosing of atracurium based on total or ideal body weight [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To compare primary endpoints (obtained in morbidly obese patients) with data of non-obese patients [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The occurrence of postoperative wound infections [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Postoperative pain scores, sedation scores and nausea scores [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • The occurrence of bleedings or thrombotic events [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • Required amounts of morphine (PCA) [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 20
Study Start Date: November 2009
Study Completion Date: April 2010
Primary Completion Date: April 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Atracurium, TBW
Dose of atracurium 0.5 mg/kg based on total body weight
Drug: Atracurium, TBW
Dose atracurium 0.5 mg/kg based on total body weight
Active Comparator: Atracurium IBW
dose 0.5 mg/kg based on ideal body weight
Drug: Atracurium, TBW
Dose atracurium 0.5 mg/kg based on total body weight

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01097148

Locations
Netherlands
St. Antonius Hospital
NIeuwegein, Netherlands, 3435EM
Sponsors and Collaborators
St. Antonius Hospital
Investigators
Principal Investigator: Simone van Kralingen, MD St. Antonius Hospital
  More Information

No publications provided

Responsible Party: S. van Kralingen, St. Antonius Hospital
ClinicalTrials.gov Identifier: NCT01097148     History of Changes
Other Study ID Numbers: V.09.231/R-09
Study First Received: March 31, 2010
Last Updated: October 12, 2010
Health Authority: Netherlands: Medical Ethics Review Committee (METC)

Keywords provided by St. Antonius Hospital:
Obese
Atracurium
Cefazolin
Morfine
Nadroparin

Additional relevant MeSH terms:
Obesity
Overnutrition
Nutrition Disorders
Overweight
Body Weight
Signs and Symptoms
Atracurium
Nicotinic Antagonists
Cholinergic Antagonists
Cholinergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Neuromuscular Nondepolarizing Agents
Neuromuscular Blocking Agents
Neuromuscular Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on April 17, 2014