Peripheral targeting of inhaled recombinant human deoxyribonuclease in stable cystic fibrosis patients

ISRCTN	ISRCTN64225851
DOI	https://doi.org/10.1186/ISRCTN64225851
Protocol serial number	2412325-3; NTR912
Sponsor	Erasmus Medical Centre (The Netherlands)
Funders	Roche Nederland B.V. (The Netherlands), Erasmus Medical Centre (The Netherlands)

Submission date: 07/03/2007
Registration date: 07/03/2007
Last edited: 12/08/2008

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

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Marije Bakker
Scientific

Division of Pediatric Respiratory Medicine, Room Sb-2666
Erasmus Medical Centre
Sophia Children's Hospital
Dr. Molenwaterplein 60
Rotterdam
3015 GJ
Netherlands

Phone	+31 (0)10 463 6683
Email	e.bakker@erasmusmc.nl

Study information

Primary study design	Interventional
Study design	Randomised, active controlled, parallel group, double blinded, multicentre trial
Secondary study design	Randomised controlled trial
Scientific title
Study objectives	Recombinant human deoxyribonuclease (rhDNase) targeted to the peripheral airways improves lung function in children with cystic fibrosis (CF) and a stable clinical condition.
Ethics approval(s)	Ethics approval received from the Medical Ethical Committee of Erasmus MC Rotterdam on the 26th April 2007.
Health condition(s) or problem(s) studied	Cystic fibrosis
Intervention	25 patients will receive four weeks of treatment with inhaled rhDNase targeted to the peripheral airways and 25 patients will receive four weeks of treatment with inhaled rhDNase targeted to the central airways. The central airways regimen is aimed to simulate equal deposition pattern as compared to conventional maintenance therapy. The peripheral airway regimen deposits a greater percentage of the medication in the peripheral airways.
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 forced expiratory flow (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. Other values obtained in the flow volume curve: 2.1. Maximum mean expiratory flow (MMEF25-75) 2.2. Forced expiratory volume in one second (FEV1) 2.3. Forced Vital Capacity (FVC) 3. Other study parameters, such as use of antibiotics and number of exacerbations (if applicable)
Completion date	01/05/2008

Eligibility

Participant type(s)	Patient
Age group	Child
Lower age limit	6 Years
Upper age limit	18 Years
Sex	Not Specified
Target sample size at registration	50
Key inclusion criteria	1. Age between six and 18 years old 2. Diagnosis of CF confirmed by sweat-test and/or deoxyribonucleic acid (DNA) analysis and/or electro-physiology testing (nasal potential difference measurement) 3. Routine treatment with rhDNase once daily, started at least one month before enrolment in the study 4. Stable condition, in this study defined as: no intravenous (i.v.) antibiotics (hospital or at home) in the previous month and constant medication regime during the previous two weeks (for example: no additional oral antibiotics course, no newly started inhaled or systemic corticosteroids etc.,) 5. Ability to perform lung function tests (assessed by trained lung function technician) 6. Lung function: forced vital capacity (FVC) greater than 40% predicted 7. Signed written informed consent
Key exclusion criteria	1. Inability to follow instructions of the investigator 2. Inability to inhale rhDNase 3. Clinical condition not stable, as assessed by the patients paediatrician 4. Concomitant medical conditions that effect inhaled treatment (e.g. cleft palate, severe malacia) 5. Current respiratory tract infection 6. Pulmonary complications that might put the patient at risk to participate in the study 7. Neuromuscular disease 8. Poor compliance with treatment as assessed by the patients paediatrician 9. Active allergic bronchopulmonary aspergillosis (ABPA) defined as an oral course of prednisone for ABPA within the last three months
Date of first enrolment	01/05/2007
Date of final enrolment	01/05/2008

Locations

Countries of recruitment

Italy
Netherlands

Study participating centre

Division of Pediatric Respiratory Medicine, Room Sb-2666

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