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Cystic FibrosisPhase 2EPICNCT00097773

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

A Phase 2 study testing Tobramycin solution for inhalation (TOBI) and Oral ciprofloxacin in people with Cystic Fibrosis and Pulmonary Disease, Chronic Obstructive, run by Seattle Children's Hospital at 54 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Cystic fibrosis (CF) is a chronic disease that significantly affects an individual's lung function. Antibiotic medications have been proven effective at reducing Pseudomonas aeruginosa (PA) infection, which is one of the main causes of death in individuals with CF. Read more about this study

Who is it for?
Ages 1 year to 12 years
What is being tested?
Tobramycin solution for inhalation (TOBI) and Oral ciprofloxacin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
304 participants
Where
54 sitesUnited States
Study dates
Sep 2004to Aug 2009
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 1 year to 12 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Diagnosis of CF, as determined by the 1997 CF Consensus Conference criteria: sweat chloride level greater than 60 milliequivalent/liter (mEq/L) by quantitative pilocarpine iontophoresis; or a genotype with two identifiable mutations consistent with CF; or an abnormal nasal transepithelial potential difference and one or more clinical features consistent with CF
  • For participants greater than 15 months of age: documented new onset of positive oropharyngeal, sputum, or lower respiratory tract culture for PA within 6 months of study entry, defined as either: 1) first lifetime documented PA positive culture; or 2) PA recovered after at least a 2-year history of PA negative respiratory cultures (at least one culture per year)
  • For participants 12-15 months of age: at least one documented positive oropharyngeal, sputum, or lower respiratory tract culture for PA since birth or CF diagnosis
  • Clinically stable with no evidence of any significant respiratory symptoms or chest radiograph findings at screening that would require administration of intravenous anti-pseudomonal antibiotics, oxygen supplementation, or hospitalization

Who cannot join

  • History of aminoglycoside hypersensitivity or adverse reaction to inhaled aminoglycoside
  • History of hypersensitivity or adverse reaction to ciprofloxacin or other fluoroquinolone medications
  • History of persistent, unresolved hearing loss documented by audiometric testing on at least two occasions and not associated with middle ear disease or an abnormal tympanogram
  • Abnormal kidney function at study entry (defined as a serum creatinine level greater than 1.5 times the upper limit of normal for participant's age)
  • Abnormal liver function test results at study entry (defined as alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) levels greater than two times the upper limit of normal range)
  • Use of any investigational drug within 30 days of study entry
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  • Use of loop diuretics, phenytoin, warfarin, theophylline, or other methylxanthines within 30 days of study entry
  • Use of more than one course of intravenous anti-pseudomonal antibiotics (at least 10 continuous days of medication use) or more than one course of inhaled anti-pseudomonal antibiotics (at least 28 continuous days of medication use) within 2 years of study entry; intravenous or inhaled anti-pseudomonal antibiotics must be stopped at least 30 days prior to study entry
  • Chronic macrolide use (more than 90 day duration) in the 3 months prior to study entry
  • Presence of a condition or abnormality that would compromise the participant's safety or the quality of the study data, in the opinion of the investigator

Trial locations and contacts

54 sites in 1 country.

54 sites in 1 country

United States54 sites

  • Children's Hospital Medical Center of Akron

    Akron, Ohio, 44308

  • Albany Medical College

    Albany, New York, 12208

  • University of Michigan

    Ann Arbor, Michigan, 48109-0212

  • Emory University Cystic Fibrosis Center

    Atlanta, Georgia, 30322

  • Medical College of Georgia

    Augusta, Georgia, 30912

  • Children's Hospital Denver

    Aurora, Colorado, 80045

  • Johns Hopkins University

    Baltimore, Maryland, 21287

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35233

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Children's Hospital, Boston

    Boston, Massachusetts, 02115

  • Vermont Children's Hospital at Fletcher Allen Health Care

    Burlington, Vermont, 05401

  • University of North Carolina, Chapel Hill

    Chapel Hill, North Carolina, 27599

  • University of Virginia

    Charlottesville, Virginia, 22908

  • Children's Memorial Hospital

    Chicago, Illinois, 60614

  • Rainbow Babies & Children's Hospital

    Cleveland, Ohio, 44106

  • Children's Hospital

    Columbus, Ohio, 43205

  • Children's Medical Center

    Dayton, Ohio, 45404

  • Children's Hospital of Michigan

    Detroit, Michigan, 48201

  • Cook Children's Medical Center

    Fort Worth, Texas, 76104

  • Spectrum Health Hospitals - DeVos Children's

    Grand Rapids, Michigan, 49503

  • Penn State Milton S. Hershey Medical Center

    Hershey, Pennsylvania, 17033

  • Texas Children's Hospital

    Houston, Texas, 77030

  • Riley Hospital/Indiana University

    Indianapolis, Indiana, 46202

  • University of Iowa

    Iowa City, Iowa, 52242

  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Nemours Children's Clinic

    Jacksonville, Florida, 32207

  • Children's Mercy Hospital

    Kansas City, Missouri, 64108

  • Dartmouth-Hitchcock Medical Center

    Lebanon, New Hampshire, 03756-0001

  • University of Kentucky

    Lexington, Kentucky, 40536-0284

  • Monmouth Medical Center

    Long Branch, New Jersey, 07740

  • Children's Hospital of Los Angeles

    Los Angeles, California, 90027

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • LeBonheur Children's Medical Center

    Memphis, Tennessee, 38105

  • Children's Hospital of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Children's Hospitals & Clinics

    Minneapolis, Minnesota, 55102

  • Vanderbilt University Medical Center

    Nashville, Tennessee, 37232-9500

  • Northern California Kaiser Cystic Fibrosis Center

    Oakland, California, 94611

  • University of Nebraska

    Omaha, Nebraska, 68198-5190

  • Stanford University

    Palo Alto, California, 94304-5786

  • St. Christopher's Hospital for Children

    Philadelphia, Pennsylvania, 19134-1095

  • Children's Hospital of Pittsburgh

    Pittsburgh, Pennsylvania, 15213

  • Maine Medical Center

    Portland, Maine, 04102

  • Oregon Health Sciences University

    Portland, Oregon, 97239

  • University of Rochester

    Rochester, New York, 14642

  • University of Utah

    Salt Lake City, Utah, 84106

  • University of California, San Francisco

    San Francisco, California, 94143

  • Children's Hospital & Regional Medical Center

    Seattle, Washington, 98105

  • Cardinal Glennon Children's Hospital

    St Louis, Missouri, 63104

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • All Children's Hospital Cystic Fibrosis Center

    St. Petersburg, Florida, 33701

  • State University of New York Upstate Medical University

    Syracuse, New York, 13210

  • New York Medical College

    Valhalla, New York, 10595

  • duPont Hospital for Children

    Wilmington, Delaware, 19803

  • University of Massachusetts Memorial Health Care

    Worcester, Massachusetts, 06155

Other trials in United States

About this study

Official title: Effectiveness and Safety of Intermittent Antimicrobial Therapy for the Treatment of New Onset Pseudomonas Aeruginosa Airway Infection in Young Patients With Cystic Fibrosis

Cystic fibrosis (CF) is a chronic disease that significantly affects an individual's lung function. Antibiotic medications have been proven effective at reducing Pseudomonas aeruginosa (PA) infection, which is one of the main causes of death in individuals with CF. The purpose of this study is to compare the effectiveness of treatment based on quarterly culture results versus consistent quarterly antibiotic treatment at reducing PA infection in children with CF.

Read the detailed description

CF is an inherited disease that causes mucus to build up in the lungs and digestive tract, which can cause lung infections and digestive problems. It is the most common type of chronic lung disease in children and young adults and may result in early death. There is no cure for this disease. The primary cause of death in individuals with CF is progressive obstructive pulmonary disease associated with chronic Pseudomonas aeruginosa (PA) infection. PA infection can occur early in life and can become highly resistant to antibiotics. Once an individual has been diagnosed with chronic PA infection, it is almost impossible to manage effectively. The need exists for an effective treatment to control and eliminate PA infection. Past research has shown that if PA infection is treated early, there is a greater likelihood that it may be eliminated completely. This study will examine two treatment regimens to compare which is more effective at eliminating PA infection. In the first regimen, participants will receive antibiotic treatment at various times throughout the study, based on findings of PA respiratory cultures obtained on a quarterly basis. In the second regimen, participants will receive antibiotic medications in consistent, quarterly cycles throughout the study. The antibiotic medications used in this study will be ciprofloxacin and inhaled tobramycin, which will be administered with a nebulizer. Both of these medications have been proven effective at treating bacterial lung infections. The overall purpose of this study is to compare the effectiveness of culture-based treatment versus consistent treatment at reducing PA infection in children with CF.

This 18-month study will enroll children with CF. For the first 28 days of the study, all participants will receive inhaled tobramycin. For the initial 14 days of this 28-day period, half of the participants will also receive either ciprofloxacin or placebo. If respiratory cultures after three weeks of treatment confirm the presence of PA, participants will receive tobramycin for an additional 28 days. Participants will then be randomly assigned to one of four treatment options: tobramycin and placebo for six consecutive quarterly cycles; tobramycin and ciprofloxacin for six consecutive quarterly cycles; tobramycin and placebo only when PA is found during quarterly respiratory cultures; or tobramycin and ciprofloxacin only when PA is found during quarterly respiratory cultures.

At the first study visit, participants will undergo a physical examination, a chest x-ray, and a review of their medical history. Lung function will be measured via spirometry (in children greater than four years of age who are able to perform spirometry), and hearing ability will be measured via audiometry (at selected sites). Blood will be drawn for laboratory tests, and a specimen will be obtained for a respiratory culture. Subsequent study visits will take place at Day 21, Weeks 10, 22, 34, 46, 58, and 70. At each visit, participants will undergo a physical examination and a spirometry test (as appropriate), and a respiratory specimen for PA culture and blood will again be collected. Participants will be required to maintain a medication diary throughout the study, and they will be contacted between visits to review medication adherence and test results.

Being tested
Tobramycin solution for inhalation (TOBI), Oral placebo, Oral ciprofloxacin
Keywords
Lung Diseases, Chronic Obstructive Pulmonary Disease
Medical subject headings
Cystic Fibrosis, Pulmonary Disease, Chronic Obstructive, Lung Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Tobramycin solution for inhalation (TOBI)Drug

    Also called TOBI, TIS

    Tobramycin solution for inhalation, 300 mg, administered twice daily for 28 days administered only when quarterly respiratory cultures are found positive for Pa.

  • Oral placeboDrug

    Also called Placebo

    Oral placebo for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive placebo, twice daily.

  • Oral ciprofloxacinDrug

    Also called Cipro, Ciprofloxacin

    Oral ciprofloxacin for six consecutive quarterly cycles. For the initial 14 days of the 28-day treatment period, the participants will receive oral ciprofloxacin, 15-20 mg/kg/dose, twice daily.

Study groups in NCT00097773
Study groupRoleWhat they receive
Cycled TOBI & placeboPlacebo comparatorTobramycin inhalation solution and oral placebo for six consecutive quarterly cycles
Receives: Drug: Tobramycin solution for inhalation (TOBI); Drug: Oral placebo
Cycled TOBI & oral ciprofloxacinActive comparatorTobramycin solution for inhalation and oral ciprofloxacin for six consecutive quarterly cycles.
Receives: Drug: Tobramycin solution for inhalation (TOBI); Drug: Oral ciprofloxacin
Culture based TOBI & placeboPlacebo comparatorTobramycin solution for inhalation and oral placebo administered only when quarterly respiratory cultures are found positive for Pa.
Receives: Drug: Tobramycin solution for inhalation (TOBI); Drug: Oral placebo
Culture based TOBI & oral ciproActive comparatorTobramycin solution for inhalation and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pa.
Receives: Drug: Tobramycin solution for inhalation (TOBI); Drug: Oral ciprofloxacin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Number of Participants With a Pulmonary Exacerbation Requiring IV Antibiotics or Hospitalization

    The primary comparison is between the pooled culture-based group and the pooled cycled group. 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.

    Measured: Measured over the 18 month study

Secondary outcomes (2)

  1. Proportion of Participants With a Pa Positive Culture

    Proportion of participants with a Pa positive culture compared between (1) the pooled cycled therapy group (n=152) and pooled culture-based therapy group (n=152), and (2) between the pooled oral placebo (n=152)and pooled cipro groups (n=152).

    Participants are included once in the cycled and culture-based columns, and once in the oral cipro and placebo columns

    Measured: Week 10 (after initial treatment course for Pa) through Month 18

  2. Number of Participants With a Pulmonary Exacerbation Requiring Oral, Inhaled, or Oral Antibiotics

    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.

    Measured: Measured over the 18 month time period

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Dec 2004 (estimated)
  2. Study startSep 2004
  3. Primary completionJun 2009
  4. Study completionAug 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Prevention
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
304 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00097773
Sponsor's protocol ID
169
Other IDs
U01HL080310
Acronym
EPIC
Status last verified
Jan 2014
First submitted
30 Nov 2004
Last updated
28 Feb 2014
Data monitoring committee
Yes

Publications

  • Treggiari MM, Rosenfeld M, Mayer-Hamblett N, Retsch-Bogart G, Gibson RL, Williams J, Emerson J, Kronmal RA, Ramsey BW; EPIC Study Group. Early anti-pseudomonal acquisition in young patients with cystic fibrosis: rationale and design of the EPIC clinical trial and observational study'. Contemp Clin Trials. 2009 May;30(3):256-68. doi: 10.1016/j.cct.2009.01.003. Epub 2009 Jan 15.

    PubMed 19470318

  • Treggiari MM, Retsch-Bogart G, Mayer-Hamblett N, Khan U, Kulich M, Kronmal R, Williams J, Hiatt P, Gibson RL, Spencer T, Orenstein D, Chatfield BA, Froh DK, Burns JL, Rosenfeld M, Ramsey BW; Early Pseudomonas Infection Control (EPIC) Investigators. Comparative efficacy and safety of 4 randomized regimens to treat early Pseudomonas aeruginosa infection in children with cystic fibrosis. Arch Pediatr Adolesc Med. 2011 Sep;165(9):847-56. doi: 10.1001/archpediatrics.2011.136.

    PubMed 21893650

  • Sanders DB, Emerson J, Ren CL, Schechter MS, Gibson RL, Morgan W, Rosenfeld M; EPIC Study Group. Early Childhood Risk Factors for Decreased FEV1 at Age Six to Seven Years in Young Children with Cystic Fibrosis. Ann Am Thorac Soc. 2015 Aug;12(8):1170-6. doi: 10.1513/AnnalsATS.201504-198OC.

    PubMed 26288390

  • Mayer-Hamblett N, Kloster M, Rosenfeld M, Gibson RL, Retsch-Bogart GZ, Emerson J, Thompson V, Ramsey BW. Impact of Sustained Eradication of New Pseudomonas aeruginosa Infection on Long-term Outcomes in Cystic Fibrosis. Clin Infect Dis. 2015 Sep 1;61(5):707-15. doi: 10.1093/cid/civ377. Epub 2015 May 13.

    PubMed 25972024

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Tobramycin solution for inhalation (TOBI) and Oral ciprofloxacin in people with Cystic Fibrosis and Pulmonary Disease, Chronic Obstructive, run by Seattle Children's Hospital at 54 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 4 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Feb 2014. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 54 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 7 Nov 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Participants With a Pulmonary Exacerbation Requiring IV Antibiotics or Hospitalization (time frame: Measured over the 18 month study). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00097773, which also lists 4 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2014.

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