|- candidate number||1906|
|- NTR Number||NTR553|
|- Date ISRCTN created||14-feb-2006|
|- date ISRCTN requested||13-jan-2006|
|- Date Registered NTR||29-dec-2005|
|- Secondary IDs||MEC-2005-308 |
|- Public Title||DIEPTE-study: DNase Inhalation in cf Exacerbations, Peripherally Targeted.|
|- Scientific Title||Efficacy of RhDNase targeted to the peripheral airways in CF exacerbations.
A randomized controlled clinical trial.|
|- hypothesis||Based on earlier studies it is likely that current rhDNase inhalation in children during exacerbations is relatively inefficient. We hypothesize that the efficacy of rhDNase treatment during exacerbations can be improved by targeting the peripheral airways more efficiently in CF. |
To obtain an optimal lung deposition of rhDNase in children with CF during an exacerbation, the mean particle size of aerosols should be smaller than commonly used for adults. Furthermore, a slow inhalation maneuver should be performed to enable particles to penetrate deeply into the lung. Administration of rhDNase with a MMAD of 3,0 ėm and a slow, deep inhalation maneuver using the AkitaŽ nebulizer gives a better peripheral lung deposition in patients with CF.
Our hypothesis is that a better peripheral lung deposition will result in:
- A bigger improvement in lung function compared to conventional treatment, especially considering the measurements of the peripheral airways: FEF75, FEF75-25 (FEF = Forced Expiratory Flow rate);
- Reduction of inhomogeneity of ventilation;
- A faster improvement of clinical symptoms.
|- Healt Condition(s) or Problem(s) studied||Cystic Fibrosis (CF)|
|- 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:
ˇ Decreased exercise tolerance
ˇ Increased cough
ˇ Increased sputum / chest congestion
ˇ School or work absenteeism
ˇ Decreased appetite
ˇ Increased adventitial sounds on lung examination
ˇ 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||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).
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||1-feb-2006|
|- planned closingdate||1-jan-2008|
|- Target number of participants||40|
|- 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.|
|- Primary outcome||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 outcome||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.
|- Trial web site||N/A|
|- status||inclusion stopped: follow-up|
|- CONTACT FOR PUBLIC QUERIES||Drs. E.M. Bakker|
|- CONTACT for SCIENTIFIC QUERIES||Dr. H.A.W.M. Tiddens|
|- Sponsor/Initiator ||Erasmus Medical Center, Sophia Childrens Hospital, Department of Pediatric Pulmonology|
(Source(s) of Monetary or Material Support)
|Roche Nederland BV|
|- Brief summary|
|- Main changes (audit trail)|
|- RECORD||29-dec-2005 - 15-dec-2010|