Efficacy of peripherally targeted inhaled rhDNase for persistent obstructive asthma in childhood

ISRCTN	ISRCTN71537084
DOI	https://doi.org/10.1186/ISRCTN71537084
Clinical Trials Information System (CTIS)	2006-002337-20
Protocol serial number	2412325-2, NL612, NTR671
Sponsor	Erasmus Medical Center (The Netherlands)
Funder	Roche Nederland BV

Submission date: 09/06/2006
Registration date: 09/06/2006
Last edited: 08/01/2021

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr H.A.W.M. Tiddens
Scientific

Erasmus Medical Center
Sophia Childrens Hospital Rotterdam
Department of Pediatric Pulmonology
Dr. Molewaterplein 60
Rotterdam
3015 GJ
Netherlands

Phone	+31 (0)10 4636690
Email	h.tiddens@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Randomised controlled trial
Secondary study design	Randomised controlled trial
Scientific title	Efficacy of peripherally targeted inhaled rhDNase for persistent obstructive asthma in childhood
Study acronym	IDOL
Study objectives	Recombinant human deoxyribonuclease (rhDNase) improves lung function in children with persistent asthma who have persistent obstructive pulmonary function. Treatment of mucus impaction is an interesting alternative approach to treating peripheral airflow limitation in asthmatic patients. In severe asthma, dramatic improvement has been described in a few patients after inhalation of the mucolytic rhDNase. In addition, in pathology studies, extensive mucus plugging has been described in asthmatic patients. Based on these findings we think that additional treatment benefit can be obtained when mucus plugging is targeted as part of asthma treatment. Especially for those asthmatic children with persistent peripheral airways obstruction, rhDNase is a well known and safe drug that could be used for this treatment. Therefore we hypothesise that rhDNase has additional effect on lung function in children with persistent asthma who have persistent obstructive pulmonary function.
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Obstructive pulmonary function, asthma
Intervention	Nebulization with rhDNase or placebo once daily (each participant is treated for two weeks with rhDNase and for 2 weeks with placebo)
Intervention type	Drug
Phase	Not Specified
Drug / device / biological / vaccine name(s)	Recombinant human deoxyribonuclease (rhDNase)
Primary outcome measure(s)	Primary endpoint will be the change in FEF75 as a result of treatment. FEF75 is the most suitable endpoint since it is sensitive to peripheral airways obstruction.
Key secondary outcome measure(s)	Secondary endpoints will include: 1. Lung clearance index (LCI) measurements as assessed by multiple breath washout 2. Cumulative symptom diary scores evaluating asthma symptoms in the second week of intervention (e.g. shortness of breath, cough, exercise intolerance, bronchodilator use etc.); 3. Fraction of exhaled nitric oxide (FENO) 4. Other values obtained in the flow volume curve: FEV1, FVC, peak expiratory flow (PEF)
Completion date	01/01/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Years
Upper age limit	18 Years
Sex	All
Target sample size at registration	60
Total final enrolment	64
Key inclusion criteria	1. Aged 6 - 18 years 2. Asthma diagnosed according to Global Initiative For Asthma (GINA) guidelines 3. Attending the outpatient clinic for at least one year 4.Treatment with at least 400 mg/day inhaled budesonide or equivalent (dose constant for at least 6 months) and bronchodilators as needed or daily 5. Clinically stable asthma while using a constant dose of Inhaled Corticosteroid (ICS) for at least three months 6. Ability to perform lung function tests (assessed by trained lung function technician) 7. Persistent peripheral airways obstruction as assessed by pulmonary function testing, defined as: dissociation between forced vital capacity (FVC) and FEF75 values: FEF75 at least 20% (absolute % predicted) lower than FVC (FEF = Forced Expiratory Flow rate) 8. FVC within normal limits (for this study defined as FVC >80% predicted)
Key exclusion criteria	1. Asthma exacerbation with hospital admission in last three months 2. Intensive care unit (ICU) admission for asthma within the last year 3. Current respiratory tract infection 4. Inability to follow instructions of the investigator 5. Inability to inhale rhDNase 6. Concomitant medical conditions that can affect inhaled treatment (e.g. cleft palate, severe malacia) 7. Neuromuscular disease 8. Smoking
Date of first enrolment	01/09/2006
Date of final enrolment	01/01/2008

Locations

Countries of recruitment

Netherlands

Study participating centre

Erasmus Medical Center

Rotterdam
3015 GJ
Netherlands

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	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	01/08/2013	08/01/2021	Yes	No

Editorial Notes

08/01/2021: The following changes have been made:
1. Publication reference added.
2. The final enrolment number has been added from the reference.
3. The NTR numbers have been added.
4. The EudraCT number has been added.