Clinical trial NCT01694069: Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis
Official title: Continuous Infusion Piperacillin-Tazobactam for the Treatment of Pulmonary Exacerbations in Patients With Cystic Fibrosis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Cystic Fibrosis
Keywords: piperacillin
tazobactam
pseudomonas aeruginosa
cystic fibrosis
pulmonary exacerbation
continuous infusion
beta lactam
Lead sponsor: West Virginia University
Sponsor class: OTHER
First posted: 2012-09-26
Enrollment: 6
Sex: ALL
Minimum age (years): 8
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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).

Eligibility 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

Primary outcomes:
measure: Change in Forced Expiratory Volume at One Second (FEV1)
timeFrame: Baseline, Day 0, and Day 14
Secondary outcomes:
measure: Piperacillin Serum Concentrations
timeFrame: Day 3
measure: Time to Next Pulmonary Exacerbation
timeFrame: Patients will be followed up to 52 weeks from time of enrollment
measure: Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score
timeFrame: Day 0 and day 14
measure: Change in Sputum Density of Pseudomonas Aeruginosa
timeFrame: Day 0, day 3, and day 14
measure: Change in Weight
timeFrame: Day 0 and day 14
measure: Time to Defervescence
timeFrame: Day 0 to day 14
measure: Time to Normalization of White Blood Cell Count
timeFrame: Day to day 14
measure: Clinical Failure of Treatment
timeFrame: Day 14
Other outcomes:
Locations:
city: Morgantown
country: United States
facility: West Virginia University Healthcare
state: West Virginia
Study officials:
affiliation: West Virginia University Healthcare
name: Lisa Biondo, PharmD
role: PRINCIPAL_INVESTIGATOR
References: