Cystic Fibrosis. Respiratory disease in patients with cystic fibrosis (CF) is characterized by an abnormal composition of the epithelial lining fluid. As a result patients develop chronic airway infection and inflammation that starts early in life. The sputum in CF is rich in leukocyte-derived DNA which greatly contributes to abnormal viscoelasticity of the CF sputum. This purulent, infected sputum can obstruct the airways. In addition to this chronic state patients can develop exacerbations of
Conditions
Interventions
The intervention in this study is the peripheral deposition of rhDNase, using the Akita nebulizer.
All patients use DNase as maintenance therapy, thus this medication is not an intervention.
Sponsors
Roche Nederland B.V.
Eligibility
Inclusion criteria
Inclusion criteria: The criteria of inclusion will be the following: 1. Age between 6 and 18 years old; 2. Diagnosis of CF confirmed by sweat-test and/or DNA analysis and/or electro physiology testing (nasal potential difference measurement); 3. Admission to hospital because of a pulmonary exacerbation requiring treatment with iv antibiotics. Criteria for a pulmonary exacerbation will be based on the definition of exacerbation by Rosenfeld et al. and will include at least three of the following: · Decreased exercise tolerance · Increased cough · Increased sputum / chest congestion · School or work absenteeism · Decreased appetite · Increased adventitial sounds on lung examination · Decrease in FEV1 (% predicted) 4. Enrolment in the study between 1 to 5 days after admission for an exacerbation; 5. Routine treatment with rhDNase once daily, started at least two weeks before enrolment in the study; 6. Ability to perform lung function tests (assessed by trained lung function technician); 7. Lung function: FVC >= 30% predicted; 8. Signed written informed consent.
Exclusion criteria
Exclusion criteria: The following exclusion criteria will be used: 1. Inability to follow instructions of the investigator; 2. Inability to inhale rhDNase; 3. Concomitant medical conditions that effect inhaled treatment (e.g. cleft palate, severe malacia); 4. Pulmonary complications that might put the patient at risk to participate in the study; 5. Deterioration primarily related to ABPA (allergic bronchopulmonary aspergillosis).
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Disease is most prominent in the peripheral airways in CF. Therefore our primary outcome measurement will be focussed on the periphery of the lung, using FEF75 and FEF75-25 (assessed by spirometry). FEF75 and FEF75-25 measured on study day 12 (after 7 days of treatment with Akita) is our primary outcome parameter. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measurements will include: 1. Other values obtained in the flow volume curve: FVC, FEV1; 2. Lung inhomogeneity measurements; 3. Nightly oxygen saturation profile; 4. Symptom scores evaluating pulmonary symptoms (e.g. cough, increased sputum); 5. Lung function measurements at discharge; 6. Lung function measurements on day 5 (end of run-in) and day 6 (first day of treatment with study drug), to assess a possible short-term effect of the peripherally deposited rhDNase. | — |
Contacts
Public ContactE.M. Bakker
Erasmus Medical Center, Sophia Children’s Hospital, Department of Pediatric Pulmonology (room Sb-2666) Dr. Molenwaterplein 60
Outcome results
None listed