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

This study has been terminated.
(Recruitment was not sufficient to complete the study)
Sponsor:
Information provided by (Responsible Party):
Lisa Biondo, West Virginia University
ClinicalTrials.gov Identifier:
NCT01694069
First received: September 19, 2012
Last updated: March 14, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Cystic Fibrosis
Drug: Piperacillin-tazobactam combination product
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Continuous Infusion Piperacillin-Tazobactam for the Treatment of Pulmonary Exacerbations in Patients With Cystic Fibrosis

Resource links provided by NLM:


Further study details as provided by West Virginia University:

Primary Outcome Measures:
  • Change in FEV1 [ Time Frame: Baseline, Day 0, and Day 14 ] [ Designated as safety issue: No ]
    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:
  • Piperacillin serum concentrations [ Time Frame: Day 3 ] [ Designated as safety issue: Yes ]

    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

  • Time to next pulmonary exacerbation [ Time Frame: Patients will be followed up to 52 weeks from time of enrollement ] [ Designated as safety issue: Yes ]
    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.

  • Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score [ Time Frame: Day 0 and day 14 ] [ Designated as safety issue: No ]
    The validated CFQ-R will be administered to patients at time of enrollment at end of therapy

  • Change in sputum density of Pseudomonas aeruginosa [ Time Frame: Day 0, day 3, and day 14 ] [ Designated as safety issue: No ]
    Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy

  • Change in weight [ Time Frame: Day 0 and day 14 ] [ Designated as safety issue: No ]
    The change in weight will be documented from enrollment to end of therapy

  • Time to defervescence [ Time Frame: Day 0 to day 14 ] [ Designated as safety issue: No ]
    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.

  • Time to normalization of white blood cell count [ Time Frame: Day to day 14 ] [ Designated as safety issue: No ]
    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.

  • Clinical failure of treatment [ Time Frame: Day 14 ] [ Designated as safety issue: No ]
    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.


Enrollment: 6
Study Start Date: September 2012
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

Ages Eligible for Study:   8 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01694069

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

No publications provided

Responsible Party: Lisa Biondo, Principal Investigator, West Virginia University
ClinicalTrials.gov Identifier: NCT01694069     History of Changes
Other Study ID Numbers: 24255
Study First Received: September 19, 2012
Last Updated: March 14, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by West Virginia University:
piperacillin
tazobactam
pseudomonas aeruginosa
cystic fibrosis
pulmonary exacerbation
continuous infusion
beta lactam

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

ClinicalTrials.gov processed this record on October 28, 2014