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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01694069
Recruitment Status : Terminated (Recruitment was not sufficient to complete the study)
First Posted : September 26, 2012
Last Update Posted : March 18, 2014
Information provided by (Responsible Party):
Lisa Biondo, West Virginia University

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.

Condition or disease Intervention/treatment Phase
Cystic Fibrosis Drug: Piperacillin-tazobactam combination product Phase 4

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  (Clinical Trial)
Actual Enrollment : 6 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Continuous Infusion Piperacillin-Tazobactam for the Treatment of Pulmonary Exacerbations in Patients With Cystic Fibrosis
Study Start Date : September 2012
Estimated Primary Completion Date : March 2014
Estimated Study Completion Date : December 2014

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
Drug: Piperacillin-tazobactam combination product
400 mg/kg/day as either intermittent or continuous infusion
Other Name: 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
Drug: Piperacillin-tazobactam combination product
400 mg/kg/day as either intermittent or continuous infusion
Other Name: Zosyn

Primary Outcome Measures :
  1. Change in 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

Secondary Outcome Measures :
  1. 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

  2. Time to next pulmonary exacerbation [ Time Frame: Patients will be followed up to 52 weeks from time of enrollement ]
    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.

  3. 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

  4. 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

  5. Change in weight [ Time Frame: Day 0 and day 14 ]
    The change in weight will be documented from enrollment to end of therapy

  6. 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.

  7. 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.

  8. 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.

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Ages Eligible for Study:   8 Years and older   (Child, Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01694069

United States, West Virginia
West Virginia University Healthcare
Morgantown, West Virginia, United States, 26505
Sponsors and Collaborators
West Virginia University
Principal Investigator: Lisa Biondo, PharmD West Virginia University Healthcare

Responsible Party: Lisa Biondo, Principal Investigator, West Virginia University Identifier: NCT01694069     History of Changes
Other Study ID Numbers: 24255
First Posted: September 26, 2012    Key Record Dates
Last Update Posted: March 18, 2014
Last Verified: March 2014

Keywords provided by Lisa Biondo, West Virginia University:
pseudomonas aeruginosa
cystic fibrosis
pulmonary exacerbation
continuous infusion
beta lactam

Additional relevant MeSH terms:
Cystic Fibrosis
Pathologic Processes
Pancreatic Diseases
Digestive System Diseases
Lung Diseases
Respiratory Tract Diseases
Genetic Diseases, Inborn
Infant, Newborn, Diseases
Penicillanic Acid
Piperacillin, tazobactam drug combination
Anti-Bacterial Agents
Anti-Infective Agents
beta-Lactamase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action