Condition category
Nutritional, Metabolic, Endocrine
Date applied
14/02/2006
Date assigned
14/02/2006
Last edited
30/09/2014
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Dr E.M. Bakker

ORCID ID

Contact details

Erasmus Medical Center
Sophia Children’s 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 measures

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

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

Sponsor information

Organisation

Erasmus Medical Centre, Sophia Children’s Hospital (Netherlands)

Sponsor details

Department of Pediatric Pulmonology
Dr Molenwaterplein 60
Rotterdam
3015 GJ
Netherlands

Sponsor type

Hospital/treatment centre

Website

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

Results - basic reporting

Publication summary

2014 results in: http://www.ncbi.nlm.nih.gov/pubmed/23913868

Publication citations

  1. 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.

Additional files

Editorial Notes