Optimizing Dosing Regimen of Piperacillin/Tazobactam for Nosocomial Pneumonia

NCT ID: NCT01796717

Last Updated: 2016-02-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 50 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-03-31
• Study Completion Date: 2016-12-31

Brief 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.

Detailed 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.

Conditions

Nosocomial Pneumonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

C Group

Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes

Group Type: ACTIVE_COMPARATOR

C Group

Intervention Type: DRUG

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

Group Type: EXPERIMENTAL

E Group

Intervention Type: DRUG

Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours

Interventions

C Group

Controlled group will receive piperacillin/tazobactam of 4.5g Q6h, intermittent infusion for 30 minutes

Intervention Type: DRUG

E Group

Therapy group will receive piperacillin/tazobactam of 4.5g Q6h, prolonged infusion for 4 hours

Intervention Type: DRUG

Other Intervention Names

nosocomial pneumonia; MIC; nosocomial pneumonia; MIC

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Pfizer

INDUSTRY

Sponsor Role: collaborator

Tianjin Medical University Cancer Institute and Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wang Donghao, Chief

Role: STUDY_CHAIR

Tianjin Medical University Cancer Institute and Hospital

Locations

TianjinCIH

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

TianjinCIH

Tianjin, Tianjin Municipality, China

Site Status: RECRUITING

Countries

China

Central Contacts

Wang Donghao, chief

Role: CONTACT

donghaow@medmail.com.cn

022-23340123 ext. 1021

Facility Contacts

Wang Donghao, Chief

Role: primary

donghaow@medmail.com.cn

022-23340123 ext. 1021

Wang Donghao, Chief

Role: primary

donghaow@medmail.com.cn

022-23340123 ext. 1021

References

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.

Reference Type: BACKGROUND

PMID: 20018492 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20047820 (View on PubMed)

Lorente L, Jimenez A, Martin MM, Iribarren JL, Jimenez 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.

Reference Type: BACKGROUND

PMID: 19150225 (View on PubMed)

Other Identifiers

CIH-WDH-201205001

Identifier Type: -

Identifier Source: org_study_id