Clinical trial NCT00097773
Conditions: Cystic Fibrosis Pulmonary Disease, Chronic Obstructive
Keywords: Lung Diseases Chronic Obstructive Pulmonary Disease
Sponsor: Seattle Children's Hospital
Start date: 2004-09-01; Completion date: 2009-08-01
Enrollment: 304 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief 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.

Arms: arm 1: Tobramycin inhalation solution and oral placebo for six consecutive quarterly cycles arm 2: Tobramycin solution for inhalation and oral ciprofloxacin for six consecutive quarterly cycles. arm 3: Tobramycin solution for inhalation and oral placebo administered only when quarterly respiratory cultures are found positive for Pa. arm 4: Tobramycin solution for inhalation and oral ciprofloxacin administered only when quarterly respiratory cultures are found positive for Pa.
Interventions: intervention 1: Tobramycin solution for inhalation (TOBI) intervention 2: Oral placebo intervention 3: Oral ciprofloxacin
Intervention descriptions: intervention 1: Tobramycin solution for inhalation, 300 mg, administered twice daily for 28 days administered only when quarterly respiratory cultures are found positive for Pa. intervention 2: 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. intervention 3: 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.

Protocol documents: