Pharmacokinetic of Doripenem and Piperacillin/Tazobactam in More Than 120 kg Critically Ill Patients

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
University Hospital, Montpellier
ClinicalTrials.gov Identifier:
NCT01517815
First received: January 11, 2012
Last updated: November 5, 2013
Last verified: November 2013
  Purpose

Overweight patients are susceptible to develop acute complications when they are admitted in an Intensive Care Unit (ICU). Severe infection can be associated with cardiovascular failure ('shock") and is associated with 35-50% mortality. One of the key issue to cure infection is to administer antibiotics. However, under dosing antibiotic is one of the main reason that explain treatment failure. There are very few data concerning particularities of antibiotic dosing in critically ill, overweight, patients. The aim of the present study is to describe the pharmacokinetic of two main antibiotics (doripenem and piperacillin/Tazobactam) in both overweight and non overweight critically ill patients presenting a septic shock. The investigators hypothesis is that usual dose for those antibiotic may be accurate in non overweight patients but is not in overweight patients.


Condition Intervention
Septic Shock
Drug: Doripenem or Piperacillin/Tazobactam

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Pharmacokinetic of Doripenem and Piperacillin/Tazobactam in More Than 120 kg Critically Ill Patients

Resource links provided by NLM:


Further study details as provided by University Hospital, Montpellier:

Primary Outcome Measures:
  • Time over MIC (calculated with the E-test) in overweight and non overweight critically ill patients [ Time Frame: up to Day 8 ] [ Designated as safety issue: Yes ]

Enrollment: 50
Study Start Date: February 2012
Study Completion Date: June 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: No overweight patient
Patient with weight less than or equal to 120kg
Drug: Doripenem or Piperacillin/Tazobactam

This arm is composed of 26 no overweight patients, Antibiotic (Doripenem or Piperacillin/Tazobactam) is chosen by the intensivist in charge of the case:

  • in 13 no overweight patients, Pipéracilline/tazobactam will be administered in 4g IV (1h) and then 16g/24h IV continuously. Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h.
  • in 13 patients no overweight: doripénème will be administered in 1g/8h with a 4h IV infusion. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value.
Other Name: no overweight patients pharmacokinetics
Experimental: Overweight patients
Patient with weight more than 120kg
Drug: Doripenem or Piperacillin/Tazobactam

This arm is composed of 26 overweight patients, Antibiotic (Doripenem or Piperacillin/Tazobactam) is chosen by the intensivist in charge of the case:

  • in 13 overweight patients, Pipéracilline/tazobactam will be administered in 4g IV (1h) and then 16g/24h IV continuously. Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h.
  • in 13 patients overweight: doripénème will be administered in 1g/8h with a 4h IV infusion. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value.
Other Name: overweight patients pharmacokinetics

Detailed Description:

N=52 patients divided in 4*13 patients (13 per antibiotic and per group, overweight or non overweight).

Overweight is defined by a weight over 120kg. Antibiotic chosen by the intensivist in charge of the case. Doripenem 1g/8h with a 4h IV infusion whatever the patient's weight. Piperacillin/Tazobactam 4g IV (1h) and then 16g/24h IV continuously whatever the patient's weight.

Piperacillin/Tazobactam plasma dosage: after the first dose and then every 12h. Doripenem plasma dosage: after the first dose and then twice a day, at peak and residual value.

Usual plasma and urine samples for urea, creatinine, electrolytes, platelets and bilirubin each 24h.

Microbiology: bacterial identification and MIC measurement with E-test

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

General:

  • Patients in severe sepsis or septic shock defined by Bone criteria (proved or very suspected infection with organ impairment and/or need of vasopressive agent to keep a mean arterial pressure more than 65mmHg)
  • Patient requiring a treatment by study's antibiotics
  • Informed consent signed
  • Patient must be affiliated or beneficiary of a social medical insurance
  • Participation of patient to the trial must be noted in the medical file

Specific to overweight patients: Weight > 120kg

Specific to no overweight patients: Weight less than or equal to 120kg

Exclusion Criteria:

  • Pregnant women
  • Under age patient minor
  • Patient protected by law
  • Known allergy to study's antibiotics
  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: NCT01517815

Locations
France
Saint Eloi Intensive Care Unit - Montpellier University Hospital
Montpellier, France, 34295
Sponsors and Collaborators
University Hospital, Montpellier
Investigators
Principal Investigator: Boris BJ JUNG, MD Saint Eloi Hospital - Montpellier University Hospital
  More Information

No publications provided

Responsible Party: University Hospital, Montpellier
ClinicalTrials.gov Identifier: NCT01517815     History of Changes
Other Study ID Numbers: UF 8739
Study First Received: January 11, 2012
Last Updated: November 5, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)
France: Committee for the Protection of Personnes

Keywords provided by University Hospital, Montpellier:
Septic shock
overweight
critically ill
pharmacokinetic
doripenem
piperacillin-tazobactam

Additional relevant MeSH terms:
Critical Illness
Shock, Septic
Disease Attributes
Infection
Inflammation
Pathologic Processes
Sepsis
Shock
Systemic Inflammatory Response Syndrome
Penicillanic Acid
Piperacillin
Piperacillin-tazobactam combination product
Tazobactam
Anti-Bacterial Agents
Anti-Infective Agents
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 30, 2014