Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT01467648
Other study ID # DORINOS4004
Secondary ID
Status Completed
Phase Phase 4
First received October 31, 2011
Last updated November 8, 2011
Start date October 2010
Est. completion date October 2011

Study information

Verified date November 2011
Source Prince of Songkla University
Contact n/a
Is FDA regulated No
Health authority Thailand: Ethics Committee, Faculty of Medicine, Prince of Songkhla University
Study type Interventional

Clinical Trial Summary

This is prospective and randomized study to assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.

Clinical and laboratory data such as Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture will be collected.

Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.

Doripenem pharmacokinetic study will be carried out during the doripenem therapy. Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.

Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.

The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed.

Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)


Description:

Introduction:

The treatment of resistant pathogens is becoming more difficult, and only a few novel antimicrobial agents are currently in development with activity against highly resistant Gram negative bacteria. Doripenem is a carbapenem antibacterial agent with a broad spectrum of activity against Gram-negative and Gram-positive bacteria. This agent is often used as the last line of therapy for highly resistant Gram negative bacilli nosocomial pathogens. In common with other beta-lactam, the main pharmacokinetic/pharmacodynamic (PK/PD) index that correlates with the therapeutic efficacy is the time that concentrations in the tissue and serum are above the MIC (t>MIC). However, in tropical countries the stability of carbapenem antibiotics is an important consideration when considering continuous infusion. Therefore, prolonged infusion may be a useful route of administration to maximize bactericidal activity. In addition, pharmacokinetic changes have been found for several antimicrobial agents in critically ill patients, including ventilator-associated pneumonia. However, until now we have had no data to reveal the PK/PD index of doripenem in these critically ill patients.

Objectives:

To assess the pharmacodynamics (t>MIC) of 0.5 g every 8 h of doripenem in patients with VAP following administration by a 4 h infusion or 1 h infusion.

Clinical and laboratory data: Age,Sex, Body weight, Electrolyte, Vital signs, APACHE II score, BUN, Cr, Blood culture

Drug preparation and administration:

Doripenem will be reconstituted with saline solution according to the manufacturer's guidelines and then administered to the patients by 2 regimens:

1.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 4 h every 8 h.

2.0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h.

Study design:

The study is planned as a prospective and randomized in patients with VAP. Each patients will receive doripenem in 2 regimens at room temperature (37°C) consecutively: (i) infusion of 0.5 g of doripenem for 4 h via an infusion pump at a constant flow rate every 8 h; (ii) infusion of 0.5 g of doripenem for 1 h via an infusion pump at a constant flow rate every 8 h.

Twelve patients will be enrolled in this study. After completion of the doripenem therapy for 3 days in this study, all patients will receive other sensitive antibiotics to eradicate their bacterial infections.

Sample collections:

Doripenem pharmacokinetic study will be carried out during the doripenem therapy.

Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 4 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.

Blood samples (approximately 2 ml) in group " 0.5 g of doripenem with 1 h infusion every 8 h regimen" will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.

All blood samples will be allowed to clot and then cebtrifuged at 2,000g.

The serum obtained will be stored at-80°C until analysis.

Doripenem assay:

The doripenem assays by method of Ikeda K et al. (J Chromatogr B, 2008) will be performed at Department of Medicine, Faculty of Medicine.

Clinical data and pathogens collection:

1. Initial patient demographic data (age, sex, weight, diagnosis, APACHE II scores) will be collected upon enrollment in the study.

2. The Gram negative bacilli isolated from sputum in 12 patients will be collected and the MIC of the doripenem for pathogens will be determined by E tests upon enrollment in the study.

Duration of study:

Patients will receive doripenem for 3 days

Pharmacokinetic and pharmacodynamic analysis:

Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response)

Sample Size: Twelve patients with VAP will be enrolled in this study.


Recruitment information / eligibility

Status Completed
Enrollment 12
Est. completion date October 2011
Est. primary completion date October 2011
Accepts healthy volunteers No
Gender Both
Age group 20 Years and older
Eligibility Inclusion Criteria:

- Patients aged = 20 years

- Patients who have VAP with Gram negative bacilli infections. The diagnosis of VAP was defined by a new and persistent infiltrate on chest radiography associated with at least one of the following: purulent tracheal secretions; temperature of 38.3°C or higher; a leukocyte count higher than 10,000/mm3

Exclusion Criteria:

- Patients who have documented hypersensitivity to doripenem or other carbapenems.

- Patients who have an estimated creatinine clearance of = 50 ml/min

- Patients who are in circulatory shock (defined as a systolic blood pressure of < 90 mmHg).

- Patients who are pregnant.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Open Label


Intervention

Drug:
Doripenem
(i) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h. Blood samples (approximately 2 ml)will be obtained by direct venepuncture at the following time: 0, 0.5, 1, 2, 3, 4, 4.5, 5, 6, 7 and 8 h after 7th dose of doripenem.
Doripenem
(ii) 0.5 g in 100 ml of normal saline solution and administered via an infusion pump at a constant flow rate over 1 h every 8 h. Blood samples (approximately 2 ml) will be obtained by direct venepuncture at the following time: 1, 1.5, 2, 4, 5, 6, 7 and 8 h after 7th dose of doripenem.

Locations

Country Name City State
Thailand Prince of Songkla University Hat Yai Songkla

Sponsors (2)

Lead Sponsor Collaborator
Sutep Jaruratanasirikul Prince of Songkla University

Country where clinical trial is conducted

Thailand, 

Outcome

Type Measure Description Time frame Safety issue
Primary Concentration of doripenem in plasma Concentration of doripenem in plasma will be simulated in Monte Carlo technique (Computer model) to get PK/PD index (40%T>MIC) and reported to % PTA (Probability Target Attainment) and %CFR (Cumulative Faction Response). 8 hours profile after 7th dose of doripenem No
See also
  Status Clinical Trial Phase
Completed NCT01406951 - Diagnostic Value of sTREM-1 and PCT Level as Well as CPIS Score for Ventilator-Associated Pneumonia Among ICU Sepsis Patients N/A
Completed NCT00893763 - Strategies To Prevent Pneumonia 2 (SToPP2) Phase 2
Recruiting NCT03581370 - Short Infusion Versus Prolonged Infusion of Ceftolozane-tazobactam Among Patients With Ventilator Associated-pneumonia Phase 3
Completed NCT02070757 - Safety and Efficacy Study of Ceftolozane/Tazobactam to Treat Ventilated Nosocomial Pneumonia (MK-7625A-008) Phase 3
Completed NCT03348579 - Hospital-acquired Pneumonia in Intensive Care Unit
Completed NCT04242706 - VITAL - VAP Prevention by BIP (Bactiguard Infection Protection) ETT Evac in Belgian ICUs Phase 4
Recruiting NCT05589727 - Application of Ventilator-Associated Events (VAE) in Ventilator-Associated Pneumonia (VAP) Notified in Brazil
Not yet recruiting NCT06168734 - Cefepime-taniborbactam vs Meropenem in Adults With VABP or Ventilated HABP Phase 3
Completed NCT02515448 - A Pharmacokinetic-pharmacodynamic Dose Comparison Study of 8 mg/kg of Inhaled or Parenteral Gentamicin in 12 Mechanically Ventilated Critically Ill Patients Treated for Ventilator-associated Pneumonia Phase 1
Completed NCT01972425 - Biomarker-based Exclusion of VAP for Improved Antibiotic Stewardship N/A
Completed NCT02838160 - Effectiveness of Different Educational Strategies on the KAP, Psychological and Clinical Outcomes N/A
Completed NCT00364299 - Prevention of Ventilator-Associated Pneumonia by Automatic Control of the Tracheal Tube Cuff Pressure N/A
Not yet recruiting NCT03018431 - CT Scan and Lung Ultrasonography to Improve Diagnostic of Ventilation Acquired Pneumonia in ICU N/A
Completed NCT02515617 - Medico-economic Study of the Subglottic Secretions Drainage in Prevention of Ventilator-associated Pneumonia (DEMETER) N/A
Completed NCT02583308 - Impact of the Subglottic Secretions Drainage on the Tracheal Secretions Colonisation N/A
Completed NCT02585180 - Subglottic Secretions Surveillance to Predict Bacterial Pathogens Involved in Ventilator-associated Pneumonia N/A
Recruiting NCT01546974 - Ventilator-associated Pneumonia (VAP) and Humidification System Phase 4
Completed NCT02060045 - Prevention Ventilator Associated Pneumonia N/A
Terminated NCT00543608 - Clinical Efficacy of Intravenous Iclaprim Versus Vancomycin in the Treatment of Hospital-Acquired, Ventilator-Associated, or Health-Care-Associated Pneumonia Phase 2
Completed NCT02116699 - Oropharyngeal Administration of Mother's Colostrum for Premature Infants (NS-72393-360) N/A