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

• Sponsor: West Virginia University (Other)
• Overall Status: Terminated
• CT.gov ID: NCT01694069
• Collaborator: (none)
• Enrollment: 6
• Location: 1
• Arms: 2
• Duration (Months): 12
• Patients Per Site Per Month: 0.5

Study Details

Study Description

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 Design

• Study Type: Interventional
• 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: Sep 1, 2012
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Change in Forced Expiratory Volume at One Second (FEV1) [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 [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 [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.

3. Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score [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 [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 [Day 0 and day 14]

   The change in weight will be documented from enrollment to end of therapy

6. Time to Defervescence [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 [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 [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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 8 Years and Older
• 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: West Virginia University
• ClinicalTrials.gov Identifier: NCT01694069
• Other Study ID Numbers: 24255
• First Posted: Sep 26, 2012
• Last Update Posted: Feb 1, 2022
• Last Verified: Jan 1, 2022

• 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; Tazobactam; Piperacillin; Piperacillin, Tazobactam Drug Combination

Study Results

Participant Flow

Recruitment Details	The study was terminated and the original PI has left the institution. Minimal results information is available; all efforts were made to retrieve more results information, but were unsuccessful. The available data does not indicate in which arm the participants were enrolled, therefore all available study data with be entered under All Study Participants.

Arm/Group Title	All Study Participants
Arm/Group Description	Intermittent Infusion piperacillin-tazobactam and Continuous infusion piperacillin-tazobactam were combined into the All Study Participants, because the available study data was not separated into arms. Continuous 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 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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Period Title: Overall Study
STARTED	6
COMPLETED	6
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Study Participants
Arm/Group Description	Intermittent Infusion piperacillin-tazobactam and Continuous infusion piperacillin-tazobactam were combined into the All Study Participants, because the available study data was not separated into arms. Continuous 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 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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Overall Participants	6
Age, Customized (Count of Participants)
Between 8 and 99 years	6 100%
Sex: Female, Male (Count of Participants)
Female	4 66.7%
Male	2 33.3%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%
Not Hispanic or Latino	6 100%
Unknown or Not Reported	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%
Asian	0 0%
Native Hawaiian or Other Pacific Islander	0 0%
Black or African American	0 0%
White	6 100%
More than one race	0 0%
Unknown or Not Reported	0 0%
Region of Enrollment (participants) [Number]
United States	6 100%

Outcome Measures

1. Primary Outcome

Title	Change in Forced Expiratory Volume at One Second (FEV1)
Description	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
Time Frame	Baseline, Day 0, and Day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

2. Secondary Outcome

Title	Piperacillin Serum Concentrations
Description	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 Frame	Day 3

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

3. Secondary Outcome

Title	Time to Next Pulmonary Exacerbation
Description	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.
Time Frame	Patients will be followed up to 52 weeks from time of enrollment

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

4. Secondary Outcome

Title	Change in Cystic Fibrosis Questionnaire-Revised (CFQ-R) Score
Description	The validated CFQ-R will be administered to patients at time of enrollment at end of therapy
Time Frame	Day 0 and day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

5. Secondary Outcome

Title	Change in Sputum Density of Pseudomonas Aeruginosa
Description	Sputum density of Pseudomonas aeruginosa will be determined at enrollment, day 3, and at end of therapy
Time Frame	Day 0, day 3, and day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

6. Secondary Outcome

Title	Change in Weight
Description	The change in weight will be documented from enrollment to end of therapy
Time Frame	Day 0 and day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

7. Secondary Outcome

Title	Time to Defervescence
Description	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 Frame	Day 0 to day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

8. Secondary Outcome

Title	Time to Normalization of White Blood Cell Count
Description	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.
Time Frame	Day to day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

9. Secondary Outcome

Title	Clinical Failure of Treatment
Description	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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

The study was terminated and the original PI has left the institution. No outcome measure results information is available; all efforts were to made to retrieve results information, but efforts were unsuccessful.

Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam	Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion	Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
Measure Participants	0	0

Adverse Events

Adverse Event Reporting Description	The study was terminated and the original PI has left the institution. No adverse event information is available; all efforts were to made to retrieve adverse event information, but efforts were unsuccessful.
Arm/Group Title	Intermittent Infusion Piperacillin-tazobactam		Continuous Infusion Piperacillin-tazobactam
Arm/Group Description	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 Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion		Piperacillin-tazobactam administered at a dose of 400 mg/kg/day (maximum of 16 grams) as a continuous infusion over 24 hours, once daily Piperacillin-tazobactam combination product: 400 mg/kg/day as either intermittent or continuous infusion
All Cause Mortality
	Intermittent Infusion Piperacillin-tazobactam		Continuous Infusion Piperacillin-tazobactam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intermittent Infusion Piperacillin-tazobactam		Continuous Infusion Piperacillin-tazobactam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Intermittent Infusion Piperacillin-tazobactam		Continuous Infusion Piperacillin-tazobactam
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.