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

This study has been completed.
Sponsor:
Collaborators:
National Heart, Lung, and Blood Institute (NHLBI)
Cystic Fibrosis Foundation Therapeutics
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 
Other                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 
Overall Participants Analyzed 
[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
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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 ]


  Serious Adverse Events
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Time Frame Randomization through Month 18
Additional Description No text entered.

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 PA

Serious Adverse Events
    Cycled TIS w/Placebo   Cycled TIS w/Cipro   Culture-Based TIS w/Placebo   Culture-Based TIS w/Cipro
Total, serious adverse events         
# participants affected / at risk   18/76 (23.68%)   21/76 (27.63%)   17/76 (22.37%)   27/76 (35.53%) 
Gastrointestinal disorders         
Abdominal Discomfort * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Abdominal Pain * 1         
# participants affected / at risk   2/76 (2.63%)   1/76 (1.32%)   2/76 (2.63%)   0/76 (0.00%) 
# events   2   1   2   0 
Colitis * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Constipation * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   3/76 (3.95%) 
# events   0   0   1   6 
Distal Intestinal Obstruction Syndrome * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   1   1   0 
Haematemesis * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Ileus * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Pancreatitis * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Vomiting * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
General disorders         
Chest Pain * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Fatigue * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Pyrexia * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   2/76 (2.63%)   0/76 (0.00%) 
# events   0   2   2   0 
Immune system disorders         
Drug Hypersensitivity * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Infections and infestations         
Acute Sinusitis * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Bronchiectasis * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Bronchopneumonia * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   1/76 (1.32%) 
# events   0   0   1   1 
Lobar Pneumonia * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   1/76 (1.32%)   2/76 (2.63%) 
# events   0   1   1   2 
Pneumonia * 1         
# participants affected / at risk   1/76 (1.32%)   1/76 (1.32%)   1/76 (1.32%)   1/76 (1.32%) 
# events   1   1   1   1 
Pseudomonas Infection * 1         
# participants affected / at risk   2/76 (2.63%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   2   0   0   1 
Respiratory Syncytial Virus Infection * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Streptococcal Infection * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Injury, poisoning and procedural complications         
Head Injury * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Overdose * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Skull Fracture * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Investigations         
Blood Urine Present * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Body Temperature Increased * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Breath Sounds Abnormal * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Bronchoscopy * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Forced Expiratory Volume Decreased * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   4/76 (5.26%)   0/76 (0.00%) 
# events   0   1   4   0 
Pulmonary Function Test Decreased * 1         
# participants affected / at risk   3/76 (3.95%)   2/76 (2.63%)   1/76 (1.32%)   2/76 (2.63%) 
# events   3   3   2   3 
Metabolism and nutrition disorders         
Dehydration * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Failure to Thrive * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   1   0   1 
Hypoglycaemia * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Musculoskeletal and connective tissue disorders         
Arthralgia * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   2/76 (2.63%) 
# events   0   0   0   3 
Back Pain * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Neoplasms benign, malignant and unspecified (incl cysts and polyps)         
Lung Neoplasm * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Nervous system disorders         
Convulsion * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Respiratory, thoracic and mediastinal disorders         
Atelectasis * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   1   0   1 
Cough * 1         
# participants affected / at risk   3/76 (3.95%)   5/76 (6.58%)   2/76 (2.63%)   5/76 (6.58%) 
# events   4   9   2   7 
Dyspnoea * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Haemoptysis * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Lung Infiltration * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   1/76 (1.32%)   1/76 (1.32%) 
# events   0   1   1   1 
Nasal Congestion * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Nasal Oedema * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Nasal Polyps * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Productive Cough * 1         
# participants affected / at risk   0/76 (0.00%)   2/76 (2.63%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   2   0   1 
Rales * 1         
# participants affected / at risk   2/76 (2.63%)   1/76 (1.32%)   1/76 (1.32%)   1/76 (1.32%) 
# events   2   2   1   1 
Respiratory Tract Congestion * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Skin and subcutaneous tissue disorders         
Erythema Nodosum * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Urticaria * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%) 
# events   0   0   1   0 
Surgical and medical procedures         
Adenotonsillectomy * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Central Venous Catheterisation * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
Gastrointestinal Tube Insertion * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Gastrostomy Tube Insertion * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Nasal Polypectomy * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Polypectomy * 1         
# participants affected / at risk   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%) 
# events   1   0   0   0 
Sinus Operation * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   2/76 (2.63%)   1/76 (1.32%) 
# events   0   0   2   1 
Tonsillectomy * 1         
# participants affected / at risk   0/76 (0.00%)   0/76 (0.00%)   0/76 (0.00%)   1/76 (1.32%) 
# events   0   0   0   1 
Vesicoureteral Reflux Surgery * 1         
# participants affected / at risk   0/76 (0.00%)   1/76 (1.32%)   0/76 (0.00%)   0/76 (0.00%) 
# events   0   1   0   0 
* Events were collected by non-systematic assessment
1 Term from vocabulary, MedRRA




  Other Adverse Events


  Limitations and Caveats
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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
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