Contact information
Type
Scientific
Primary contact
Dr E.M. Bakker
ORCID ID
Contact details
Erasmus Medical Center
Sophia Childrens Hospital
Department of Pediatric Pulmonology (room Sb-2666)
Dr. Molenwaterplein 60
Rotterdam
3015 GJ
Netherlands
+31 (0)10 4636683
e.bakker@erasmusmc.nl
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
NTR553; MEC-2005-308
Study information
Scientific title
Added 24/08/09: Efficacy of RhDNase targeted to the peripheral airways in CF exacerbations. A randomized controlled clinical trial.
Acronym
DIEPTE
Study 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 um and a slow, deep inhalation maneuver using the Akita® nebulizer gives a better peripheral lung deposition in patients with CF.
Our hypothesis is that a better peripheral lung deposition will result in:
1. 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)
2. Reduction of inhomogeneity of ventilation
3. A faster improvement of clinical symptoms
Ethics approval
Received from local medical ethics committee
Study design
Randomised double blind active controlled parallel group trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Not specified
Trial type
Treatment
Patient information sheet
Condition
Cystic Fibrosis (CF)
Intervention
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.
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Disease is most prominent in the peripheral airways in CF. Therefore our primary outcome measurement will be focused 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 measures
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
Overall trial start date
01/02/2006
Overall trial end date
01/01/2008
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
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.
The 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:
a. Decreased exercise tolerance
b. Increased cough
c. Increased sputum / chest congestion
d. School or work absenteeism
e. Decreased appetite
f. Increased adventitial sounds on lung examination
g. 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: forced vital capacity (FVC) >/= 30% predicted
8. Signed written informed consent
Participant type
Patient
Age group
Child
Gender
Both
Target number of participants
40
Participant exclusion criteria
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 allergic bronchopulmonary aspergillosis (ABPA)
Recruitment start date
01/02/2006
Recruitment end date
01/01/2008
Locations
Countries of recruitment
Netherlands
Trial participating centre
Erasmus Medical Center
Rotterdam
3015 GJ
Netherlands
Funders
Funder type
Industry
Funder name
Roche Nederland BV (Netherlands)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/23913868
Publication citations
-
Results
Bakker EM, Volpi S, Salonini E, Müllinger B, Kroneberg P, Bakker M, Hop WC, Assael BM, Tiddens HA, Small airway deposition of dornase alfa during exacerbations in cystic fibrosis; a randomized controlled clinical trial., Pediatr. Pulmonol., 2014, 49, 2, 154-161, doi: 10.1002/ppul.22800.