Continuous Infusion Piperacillin-tazobactam for the Treatment of Cystic Fibrosis (PIPE-CF)

January 28, 2022 updated by: West Virginia University

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

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.

Study Overview

Status

Terminated

Conditions

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).

Study Type

Interventional

Enrollment (Actual)

6

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

6 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Intermittent Infusion piperacillin-tazobactam
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams), divided in four equal doses, administered over 30 minutes, four times a day
400 mg/kg/day as either intermittent or continuous infusion
Other Names:
  • Zosyn
Experimental: Continuous infusion piperacillin-tazobactam
Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily
400 mg/kg/day as either intermittent or continuous infusion
Other Names:
  • Zosyn

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Forced Expiratory Volume at One Second (FEV1)
Time Frame: Baseline, Day 0, and Day 14
FEV1 will be measured upon enrollment (day 0). FEV1 will also be measured at end of therapy (day 14). If FEV1 is available when patient was stable, prior to enrollment, this value will be treated as baseline FEV1. Change in FEV1 will be calculated from baseline (if available) to day 14 and also Day 0 to day 14
Baseline, Day 0, and Day 14

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Piperacillin Serum Concentrations
Time Frame: Day 3

Serum piperacillin concentration will be measured as follows:

  • Intermittent infusion arm: prior to dose (trough), 30 minutes (after completion of infusion), and at 4 hours
  • Continuous infusion arm: collected at the same time as in the intermittent infusion arm
Day 3
Time to Next Pulmonary Exacerbation
Time Frame: Patients will be followed up to 52 weeks from time of enrollment
Patients will be followed for time of next subsequent pulmonary exacerbation for up to 52 weeks after completion of receiving study drug. Next pulmonary exacerbation is defined as requiring admission to a hospital for receipt of I.V. antibiotics because of a diagnosis of pulmonary exacerbation.
Patients will be followed up to 52 weeks from time of enrollment
Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score
Time Frame: Day 0 and day 14
The validated CFQ-R will be administered to patients at time of enrollment at end of therapy
Day 0 and day 14
Change in Sputum Density of Pseudomonas Aeruginosa
Time Frame: Day 0, day 3, and day 14
Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy
Day 0, day 3, and day 14
Change in Weight
Time Frame: Day 0 and day 14
The change in weight will be documented from enrollment to end of therapy
Day 0 and day 14
Time to Defervescence
Time Frame: Day 0 to day 14
Temperature will be taken multiple times daily according to standard of care. If patients present febrile, time until patient is afebrile and remains afebrile for 24 hours will be recorded.
Day 0 to day 14
Time to Normalization of White Blood Cell Count
Time Frame: Day to day 14
White blood cell (WBC) count will be measured once daily. If patient presents with WBC count greater than 11.0 x 10^3/mL, time until patient has WBC less than 11.0 x 10^3/mL will be recorded.
Day to day 14
Clinical Failure of Treatment
Time Frame: Day 14
Failure of treatment will be defined as patient needing I.V. antibiotics beyond the 14 days allowed in this study. The primary medical team (along with a blinded investigator) treating the patient will determine whether patient requires additional therapy.
Day 14

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Lisa Biondo, PharmD, West Virginia University Healthcare

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2012

Primary Completion (Actual)

September 1, 2013

Study Completion (Actual)

September 1, 2013

Study Registration Dates

First Submitted

September 19, 2012

First Submitted That Met QC Criteria

September 24, 2012

First Posted (Estimate)

September 26, 2012

Study Record Updates

Last Update Posted (Actual)

February 1, 2022

Last Update Submitted That Met QC Criteria

January 28, 2022

Last Verified

January 1, 2022

More Information

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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