Optimizing Dosing Regimen of Piperacillin/Tazobactam for Nosocomial Pneumonia

Nosocomial Pneumonia Clinical Trial

Official title:

Optimizing Dosing Regimen of Piperacillin/Tazobactam, Prolonged Infusion vs. Regular Infusion, Every 6 Hours, for Nosocomial Pneumonia in ICU Caused by Susceptible Pathogens With Higher MIC

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01796717
• Other study ID #: CIH-WDH-201205001
• Status: Recruiting
• Phase: Phase 2/Phase 3
• First received: August 30, 2012
• Last updated: February 14, 2016
• Start date: March 2012
• Est. completion date: December 2016

Study information

• Verified date: August 2012
• Source: Tianjin Medical University Cancer Institute and Hospital
• Contact: Wang Donghao, chief
• Phone: 022-23340123
• Email: donghaow[@]medmail.com.cn
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

1. To observe clinical and bacteriologic responses of different regimens of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) for treatment of nosocomial pneumonia.

2. To describe the pharmacokinetic profile of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) in patients with nosocomial pneumonia.

3. To assess the safety profiles of piperacillin/tazobactam 4.5g q6h, prolonged or intermittent infusion in patients with nosocomial pneumonia.

Description:

Enrolled patients will be randomized into therapeutic or controlled group. Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes. Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours. The duration is 7-14 days.

Two sets of blood cultures (for aerobic and anaerobic culture) were obtained before the study and post-treatment period if first blood culture is positive. Cultures from the lower respiratory tract infection were obtained before (within 48 h) the study and on the last day of therapy. The lower respiratory tract specimens obtained either by endotracheal aspiration, bronchoalveolar lavage (BAL), a protected brush procedure (PBP) or as sputum were required to show > 25 polymorphonuclear cells and < 10 squamous epithelial cells per field (at 100× magnification).

The plasma concentration of piperacillin and tazobactam will be determined by LC/MS/MS method. The QC samples will also be analyzed simultaneously with each run for the method stability testing, according to the laboratory standard procedure.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: December 2016
• Est. primary completion date: November 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

1. Male or female, aged 18 to 70 years old.

2. Inpatients with nosocomial pneumonia or bacteremia.

i. Diagnosis of nosocomial pneumonia

1. Chest radiographic infiltrate that is new or progressive.

2. At least two or more of the following clinical findings suggesting infection.

• New onset of fever, oral temperature T>38.3? or T<36?

• Purulent sputum

• WBC > 12×10^9/L or <4×10^9/L, or band form >10%

• PaO2/FIO2<240mmHg

ii. Diagnosis of bacteremia: Positive blood culture and the isolated bacterial strain are considered to be infection cause.

3. Patients are infected by piperacillin-tazobactam susceptible pathogen with MIC=4, 8 or 16mg/L.

Exclusion Criteria:

1. The patients who received systematic antibacterial treatment more than 48 hours before enrollment and have clinical response.

2. Severe pyemia with hypotension or/and evidences of failure of organic function (shock: systolic pressure < 90mmHg or diastolic pressure < 60mmHg, requiring more than 4 hours of administration of vasopressor(s);renal impairment: urine volume < 20 ml/h or < 80 ml/4h after excluded any other potentials, acute renal failure need dialysis, CLcr<40 mL/min).

3. Documented infection caused by pathogens beyond the antibacterial spectrum of piperacillin/tazobactam.

4. Previously diagnosed condition which tend to mimic or complicate the course and evaluation of the infectious process, e.g. bronchial obstruction, obstructive pneumonia, activate pulmonary malignancy, pulmonary abscess, empyema and active tuberculosis, which might interfere the course of the infectious disease and evaluation of the disease.

5. History of allergy to penicillins.

6. Pregnancy or breast-feeding women.

7. Any conditions investigator considered might increase the risk of patients or interfere study results.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics/Dynamics Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Nosocomial Pneumonia
• Pneumonia

Intervention

Drug:
• C Group
Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes
• E Group
Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours

Locations

Country	Name	City	State
China	TianjinCIH	Tianjin	Tianjin
China	TianjinCIH	Tianjin	Tianjin

Sponsors (2)

Lead Sponsor	Collaborator
Tianjin Medical University Cancer Institute and Hospital	Pfizer

Country where clinical trial is conducted

China, 

References & Publications (3)

Lorente L, Jiménez A, Martín MM, Iribarren JL, Jiménez JJ, Mora ML. Clinical cure of ventilator-associated pneumonia treated with piperacillin/tazobactam administered by continuous or intermittent infusion. Int J Antimicrob Agents. 2009 May;33(5):464-8. doi: 10.1016/j.ijantimicag.2008.10.025. Epub 2009 Jan 15. — View Citation

Roberts JA, Kirkpatrick CM, Roberts MS, Dalley AJ, Lipman J. First-dose and steady-state population pharmacokinetics and pharmacodynamics of piperacillin by continuous or intermittent dosing in critically ill patients with sepsis. Int J Antimicrob Agents. 2010 Feb;35(2):156-63. doi: 10.1016/j.ijantimicag.2009.10.008. Epub 2009 Dec 16. — View Citation

Wang H, Chen M, Ni Y, Liu Y, Sun H, Yu Y, Yu X, Mei Y, Liu M, Sun Z, Chu Y, Hu Z, Huang X. Antimicrobial resistance among clinical isolates from the Chinese Meropenem Surveillance Study (CMSS), 2003-2008. Int J Antimicrob Agents. 2010 Mar;35(3):227-34. doi: 10.1016/j.ijantimicag.2009.11.010. Epub 2010 Jan 4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Extension of the Piperacillin / tazobactam infusion time effect evaluation	To observe clinical and bacteriologic responses of different regimens of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) for treatment of nosocomial pneumonia.	2 weeks	Yes
Secondary	Reducing antibiotic resistance	To describe the pharmacokinetic profile of piperacillin/tazobactam (4.5g q6h, prolonged or intermittent infusion) in patients with nosocomial pneumonia.	2 weeks	Yes