Comparison of Two Treatment Regimens to Reduce PA Infection in Children With Cystic Fibrosis
Condition: Cystic Fibrosis; Pulmonary Disease, Chronic Obstructive
MeSH terms: Cystic Fibrosis; Lung Diseases; Pulmonary Disease, Chronic Obstructive; Fibrosis
Study type: Interventional
Phase: Phase 2

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.
      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.
    

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.
    

Intervention name(s): Tobramycin solution for inhalation (TOBI); Oral placebo; Oral ciprofloxacin
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Tobramycin solution for inhalation, 300 mg, administered twice daily for 28 days administered only when quarterly respiratory cultures are found positive for Pa.; 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 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.
Other intervention name(s): TOBI, TIS; Placebo; Cipro; Ciprofloxacin
Intervention MeSH terms: Ciprofloxacin; Tobramycin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Lung Diseases; Chronic Obstructive Pulmonary Disease