Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis

Condition(s) targeted: Cystic Fibrosis

Intervention: Piperacillin-tazobactam combination product (Drug)

Phase: Phase 4

Status: Terminated

Sponsored by: West Virginia University

Official(s) and/or principal investigator(s):
Lisa Biondo, PharmD, Principal Investigator, Affiliation: West Virginia University Healthcare

Cystic fibrosis is an inherited disorder leading to chronic pulmonary inflammation and infection. A majority of people with cystic fibrosis have large quantities of bacteria residing in their lungs. One of the most common and harmful bacteria is called Pseudomonas aeruginosa. Patients with cystic fibrosis require frequent therapy with intravenous (I. V.) antibiotics to treat lung infections thought to be caused by Pseudomonas aeruginosa. One of the antibiotics frequently used to treat this bacteria is piperacillin-tazobactam. Piperacillin-tazobactam is thought to be the most effective when there is a constant level of drug in the body. The standard way to administer piperacillin-tazobactam is to give several grams 4 times each day as a 30 minute infusion. An alternative way to give piperacillin-tazobactam is by a continuous infusion; a continuous infusion will make it more likely that drug will remain at a constant level in the body. The objective of this study is to determine if administering piperacillin-tazobactam as a continuous infusion is more effective at treating people having a pulmonary exacerbation of cystic fibrosis than a standard 30 minute infusion, 4 times a day.

Official title: Continuous Infusion Piperacillin-Tazobactam for the Treatment of Pulmonary Exacerbations in Patients With Cystic Fibrosis

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Primary outcome: Change in FEV1

Secondary outcome:

Piperacillin serum concentrations

Time to next pulmonary exacerbation

Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score

Change in sputum density of Pseudomonas aeruginosa

Change in weight

Time to defervescence

Time to normalization of white blood cell count

Clinical failure of treatment

Detailed description: All patients will receive combination therapy to include piperacillin-tazobactam 400 mg/kg/day (based on piperacillin component, actual body weight) not to exceed 16 grams and tobramycin 12 mg/kg/day extended interval dosing (once daily). Patients randomized to the continuous infusion group will receive a one-time loading dose of 100 mg/kg over 30 minutes followed immediately by initiation of the continuous infusion. Other antibiotics with activity against Pseudomonas aeruginosa are not allowed. Patients may receive an antibiotic for treatment of Staphylococcus aureus if deemed appropriate. Other treatments for pulmonary exacerbation of cystic fibrosis will be left up to the control of the treating physician. Patients will receive a total of 14 days of therapy. If deemed appropriate, patients may be discharged to home where they will continue to receive blinded treatment via an infusion pump. Patients will be evaluated after completing their 14 day course of antibiotics (end of therapy).

Minimum age: 8 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Diagnosis of cystic fibrosis 2. 8 years of age or greater 3. Chronic or intermittent infection with Pseudomonas aeruginosa as defined by the Leeds Criteria 4. Pulmonary exacerbation as defined by Fuchs et al. Exclusion Criteria: 1. Admission for greater than 48 hours prior to enrollment 2. Isolation of Burkholderia spp. in a respiratory tract culture in the prior 12 months 3. Current treatment for allergic bronchopulmonary aspergillosis 4. Pregnant or breast feeding 5. History of solid organ transplantation 6. Renal impairment at time of randomization (< 40 mL/min as calculated by the Cockcroft-Gault equation24 ¬for adults or the Schwartz equation45 for those < 18 years of age) or receipt of hemodialysis 7. Allergy to study medication

West Virginia University Healthcare, Morgantown, West Virginia 26505, United States

Starting date: September 2012
Last updated: March 14, 2014