The Pharmacodynamics of Doripenem Between 4-hour and 1-hour Infusion in Patients With Ventilator-associated Pneumonia

NCT01467648 | Completed Phase 4

• 1 other identifier: DORINOS4004
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief 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)

Conditions

Ventilator-Associated Pneumonia

Keywords

Infection; Doripenem; Ventilator-Associated Pneumonia; pharmacokinetic; pharmacodynamic

Outcome Measures

Primary Outcomes (1)

• 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

Study Arms (2)

0.5 g by 4 hour infusion

EXPERIMENTAL

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.

Drug: Doripenem

0.5 g by 1 hour infusion

EXPERIMENTAL

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.

Drug: Doripenem

Interventions

Doripenem DRUG

(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.

Also known as: Doripenem (Doribax)

0.5 g by 4 hour infusion

Eligibility Criteria

• Age: 20 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Sutep Jaruratanasirikul: lead
• Prince of Songkla University: collaborator

Study Sites (1)

Prince of Songkla University

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

MeSH Terms

Conditions

Pneumonia, Ventilator-Associated; Infections

Interventions

Doripenem

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Sutep Jaruratanasirikul, MD

  Prince of Songkha

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: October 31, 2011
• First Posted: November 9, 2011
• Study Start: October 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: November 9, 2011

Record last verified: 2011-11

Locations

TH (1)