Population Pharmacokinetic (PK) Study of Multiple Doses of Cubicin® (Daptomycin) 10 mg/kg in Critical Care Patients Having Bacteremia, Endocarditis or Skin Soft Tissue Infections Due to Gram Positive Bacteria With Various Degrees of Renal Failure

Renal Failure Clinical Trial

— DAPTOREA  

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02142075
• Other study ID #: DAPTOREA
• Status: Completed
• Phase: Phase 3
• First received: March 12, 2014
• Last updated: October 10, 2016
• Start date: March 2014

Study information

• Verified date: October 2016
• Source: Poitiers University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: France : ANSM - Agence Nationale de Sécurité du Médicament
• Study type: Interventional

Clinical Trial Summary

Treatment of infections in critically ill patients remains a significant challenge to intensivists world-wide with persisting high mortality and morbidity. Compelling evidence suggests that source control of the pathogen and appropriate antibiotic therapy remain the most important interventions to improve patients' outcome, the latter including the administration of a suitable molecule at an optimized dosage regimen.

Daptomycin is the first representative of a new family of antibiotics, the cyclic lipopeptides. Its bactericidal effect against Gram-positive bacteria, including meticillin-resistant strains, and its low renal toxicity, make it a useful antibiotic in critically ill patients having infections due to resistant Gram positive strains.

Unfortunately, no PK study has been performed in infected critically ill patients without renal replacement therapy. A vast array of pathophysiological changes can occur in infected critically ill patients, leading to changes in volume of distribution and clearance of antibiotics in these patients, which may affect the antibiotic concentration at the target site.

It is therefore important to better characterize daptomycin PK in infected patients with various degrees of renal failure in order to define optimal dosing regimens.

This project aims to identify optimal daptomycin administration schemes in critical care patients with various degrees of renal impairment

Recruitment information / eligibility

• Status: Completed
• Enrollment: 0
• Est. primary completion date: September 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• Patients of two sexes aged 18 to 85 years,

• Hospitalized in one of the intensive care unit participating in the study,

• Under mechanical ventilation,

• Having skin or soft tissue infection, bacteremia or endocarditis caused by Gram positivebacteria susceptible to daptomycin,

• Having given written consent to participate to the study.

• Patients with severe sepsis and septic shock will also be included because it's the very population that may benefit from daptomycin treatment and it's important to get data for these patients in order to optimize their treatment.

Exclusion Criteria:

• Pregnant or lactating women

• Obese subjects (body mass index > 40 mg/m2)

• Patients requiring extrarenal replacement therapy,

• Patients having already received daptomycin during the 21 days prior to inclusion,

• Known hypersensitivity to daptomycin,

• History of myopathy

• creatine phosphokinase >5 upper limit of normal

• Patients not affiliated to a social security scheme,Patients deprived of their liberty by judicial or administrative decision

Study Design

N/A

Related Conditions & MeSH terms

• Critical Care
• Gram Positive Bacteria
• Renal Failure
• Renal Insufficiency
• Soft Tissue Infections

Intervention

Drug:
• Daptomycin

Locations

Country	Name	City	State
France	Lasocki S, University Hospital of Angers	Angers
France	Asehnoune K, University Hospital of Nantes	Nantes
France	Seguin P, University Hospital of Rennes	Rennes
France	Ferrandiere M, University Hospital of Tours	Tours

Sponsors (1)

Lead Sponsor	Collaborator
Poitiers University Hospital

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	area under the curve / minimum inhibitory concentration ratio of distribution and elimination of daptomycin in plasma and urine		12 months
Primary	Cmin and Cmax of distribution and elimination of daptomycin in plasma and urine		12 months
Primary	volume of distribution of daptomycin in plasma and urine		12 months
Primary	clearance of distribution and elimination of daptomycin in plasma and urine		12 months
Secondary	the clinical and microbiological efficacy during Daptomycine treatment and two weeks after the end of it	Patients will be considered to have clinical failure if they will have no response to the study drug on the basis of ongoing signs and symptoms of infection. Otherwise, patients will be considered to have clinical success.	12 months
Secondary	renal and muscular tolerance during Daptomycin treatment and two weeks after the end of it		12 months