DIEPTE-study: DNase Inhalation in CF Exacerbations, Peripherally Targeted

ISRCTN	ISRCTN50584238
DOI	https://doi.org/10.1186/ISRCTN50584238
Secondary identifying numbers	NTR553; MEC-2005-308

Submission date: 14/02/2006
Registration date: 14/02/2006
Last edited: 30/09/2014

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nutritional, Metabolic, Endocrine

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr E.M. Bakker
Scientific

Erasmus Medical Center
Sophia Childrens Hospital
Department of Pediatric Pulmonology (room Sb-2666)
Dr. Molenwaterplein 60
Rotterdam
3015 GJ
Netherlands

Phone	+31 (0)10 4636683
Email	e.bakker@erasmusmc.nl

Study information

Study design	Randomised double blind active controlled parallel group trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title	Added 24/08/09: Efficacy of RhDNase targeted to the peripheral airways in CF exacerbations. A randomized controlled clinical trial.
Study acronym	DIEPTE
Study objectives	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(s)	Received from local medical ethics committee
Health condition(s) or problem(s) studied	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
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 study start date	01/02/2006
Completion date	01/01/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Years
Upper age limit	18 Years
Sex	Both
Target number of participants	40
Key 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
Key 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)
Date of first enrolment	01/02/2006
Date of final enrolment	01/01/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Center

Rotterdam
3015 GJ
Netherlands

Sponsor information

Erasmus Medical Centre, Sophia Childrens Hospital (Netherlands)
Hospital/treatment centre

Department of Pediatric Pulmonology
Dr Molenwaterplein 60
Rotterdam
3015 GJ
Netherlands

"ROR"	https://ror.org/047afsm11

Funders

Funder type

Industry

Roche Nederland BV (Netherlands)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	01/02/2014		Yes	No