Comparison of Two Treatment Regimens to Reduce PA Infection in Children With Cystic Fibrosis (EPIC)

This study has been completed.
Sponsor:
Collaborators:
Cystic Fibrosis Foundation
CF Therapeutics Development Network Coordinating Center
Information provided by (Responsible Party):
Bonnie Ramsey, Seattle Children's Hospital
ClinicalTrials.gov Identifier:
NCT00097773
First received: November 30, 2004
Last updated: January 28, 2014
Last verified: January 2014
Results First Received: June 11, 2013  
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: Prevention
Conditions: Cystic Fibrosis
Pulmonary Disease, Chronic Obstructive
Interventions: Drug: Tobramycin solution for inhalation (TOBI)
Drug: Oral placebo
Drug: Oral ciprofloxacin

  Participant Flow
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Recruitment Details
Key information relevant to the recruitment process for the overall study, such as dates of the recruitment period and locations
Recruitment was conducted from December 2004 to June 2009 from 55 Cystic Fibrosis Foundation accredited clinical centers throughout the US

Pre-Assignment Details
Significant events and approaches for the overall study following participant enrollment, but prior to group assignment
No text entered.

Reporting Groups
  Description
Cycled TOBI and Oral Placebo Tobramycin solution for inhalation (TOBI) and oral placebo for six consecutive quarterly cycles
Cycled TOBI and Oral Ciprofloxacin Tobramycin solution for inhalation (TOBI) and oral ciprofloxacin for six consecutive quarterly cycles
Culture-Based TOBI and Oral Ciprofloxacin Tobramycin solution for inhalation (TOBI) and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pseudomonas aeruginosa (Pa)
Culture-Based TOBI and Oral Placebo Tobramycin solution for inhalation (TOBI) and oral placebo administered only when quarterly respiratory cultures are found positive for Pseudomonas aeruginosa (Pa)

Participant Flow:   Overall Study
    Cycled TOBI and Oral Placebo     Cycled TOBI and Oral Ciprofloxacin     Culture-Based TOBI and Oral Ciprofloxacin     Culture-Based TOBI and Oral Placebo  
STARTED     76     76     76     76  
COMPLETED     68     68     68     73  
NOT COMPLETED     8     8     8     3  
Lost to Follow-up                 2                 2                 0                 1  
Physician Decision                 2                 2                 3                 1  
Withdrawal by Subject                 3                 3                 3                 1  
Adverse Event                 0                 1                 0                 0  
Unknown                 1                 0                 2                 0  



  Baseline Characteristics
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Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to Treat

Reporting Groups
  Description
Cycled TIS w/Placebo TOBI and oral placebo for six consecutive quarterly cycles
Cycled TIS w/Cipro TOBI and oral ciprofloxacin for six consecutive quarterly cycles
Culture-Based TIS w/Placebo TOBI and oral placebo administered only when quarterly respiratory cultures are found positive for Pseudomonas aeruginosa (Pa)
Culture-Based TIS w/Cipro TOBI and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pseudomonas aeruginosa (Pa)
Total Total of all reporting groups

Baseline Measures
    Cycled TIS w/Placebo     Cycled TIS w/Cipro     Culture-Based TIS w/Placebo     Culture-Based TIS w/Cipro     Total  
Number of Participants  
[units: participants]
  76     76     76     76     304  
Age  
[units: participants]
         
<=18 years     76     76     76     76     304  
Between 18 and 65 years     0     0     0     0     0  
>=65 years     0     0     0     0     0  
Age  
[units: years]
Mean ± Standard Deviation
  5.8  ± 3.43     5.9  ± 3.28     6.0  ± 3.74     5.0  ± 3.58     5.7  ± 3.51  
Gender  
[units: participants]
         
Female     45     32     40     37     154  
Male     31     44     36     39     150  
Region of Enrollment  
[units: participants]
         
United States     76     76     76     76     304  



  Outcome Measures
  Show All Outcome Measures

1.  Primary:   Number of Participants With a Pulmonary Exacerbation Requiring IV Antibiotics or Hospitalization   [ Time Frame: Measured over the 18 month study ]

2.  Secondary:   Proportion of Participants With a Pa Positive Culture   [ Time Frame: Week 10 (after initial treatment course for Pa) through Month 18 ]

3.  Secondary:   Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics   [ Time Frame: Measured over the 18 month time period ]
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Measure Type Secondary
Measure Title Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics
Measure Description

The primary comparison is between the pooled culture-based group and the pooled cycled group. No interactions with ciprofloxacin were identified. A secondary comparison is between the pooled ciprofloxacin group vs the pooled placebo group. Descriptive results are provided for the pooled treatment groups.

Participants are represented once in the cycled and culture-based therapy columns, and once in the cipro and placebo columns.

Time Frame Measured over the 18 month time period  
Safety Issue No  

Population Description
Explanation of how the number of participants for analysis was determined. Includes whether analysis was per protocol, intention to treat, or another method. Also provides relevant details such as imputation technique, as appropriate.
Intent to treat

Reporting Groups
  Description
Cycled TIS Pooled Cycled TIS therapy group
Culture-Based TIS Pooled Culture-Based TIS therapy group
Oral Ciprofloxacin Pooled oral cipro group
Oral Placebo Pooled oral placebo group

Measured Values
    Cycled TIS     Culture-Based TIS     Oral Ciprofloxacin     Oral Placebo  
Number of Participants Analyzed  
[units: participants]
  152     152     152     152  
Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics  
[units: participants]
  70     81     83     68  


Statistical Analysis 1 for Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics
Groups [1] Cycled TIS vs. Culture-Based TIS
Method [2] Regression, Cox
P Value [3] 0.18
Hazard Ratio (HR) [4] 0.80
95% Confidence Interval ( 0.58 to 1.11 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  The analysis compared the pooled Cycled Therapy group (n=152) vs. the Pooled culture-based therapy group (n=152). The null hypothesis was no difference between groups in the risk of pulmonary exacerbation.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No interaction with ciprofloxacin usage was observed.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Hazard ratio comparing cycled to culture based therapy

Statistical Analysis 2 for Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics
Groups [1] Oral Ciprofloxacin vs. Oral Placebo
Method [2] Regression, Cox
P Value [3] 0.12
Hazard Ratio (HR) [4] 1.29
95% Confidence Interval ( 0.94 to 1.78 )
[1] Additional details about the analysis, such as null hypothesis and power calculation:
  This analysis was between the pooled oral cipro (n=152)and pooled placebo groups (n=152. Null hypothesis was no difference between groups.
[2] Other relevant method information, such as adjustments or degrees of freedom:
  No text entered.
[3] Additional information, such as whether or not the p-value is adjusted for multiple comparisons and the a priori threshold for statistical significance:
  No text entered.
[4] Other relevant estimation information:
  Hazard ratio comparing cipro to placebo.




  Serious Adverse Events


  Other Adverse Events


  More Information
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Certain Agreements:  
Principal Investigators are NOT 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.


Limitations and Caveats
Limitations of the study, such as early termination leading to small numbers of participants analyzed and technical problems with measurement leading to unreliable or uninterpretable data
No text entered.  


Results Point of Contact:  
Name/Title: Bonnie Ramsey, MD
Organization: Seattle Childrens Hospital
phone: 206-987-5725
e-mail: bonnie.ramsey@seattlechildrens.org


Publications of Results:
Other Publications:

Responsible Party: Bonnie Ramsey, Seattle Children's Hospital
ClinicalTrials.gov Identifier: NCT00097773     History of Changes
Other Study ID Numbers: 169, U01HL080310
Study First Received: November 30, 2004
Results First Received: June 11, 2013
Last Updated: January 28, 2014
Health Authority: United States: Food and Drug Administration