Cystic FibrosisPhase 4NCT00557089
The Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
A Phase 4 study testing rhDNAse in people with Cystic Fibrosis, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF). Read more about this study
- Who is it for?
- Ages 6 to 18 years
- Conditions the study is for
- Cystic Fibrosis
- What is being tested?
- rhDNAse
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 17 participants
- Where
- 1 siteCanada
- Study dates
- Jan 2008to Jun 2009
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 to 18 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of CF as defined by clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- Informed consent and verbal assent (as appropriate) has been provided by the subject's parent or legal guardian and the subject
- 6-18 years of age at enrolment
- Able to perform reproducible spirometry
- Clinically stable at enrolment
- Ability to comply with medication use, study visits and study procedures as judged by the site investigator
- FEV1 % predicted > 70 % as calculated by the Wang reference equations
Who cannot join
- Respiratory culture positive for:
- NTM within past year or AFB positive at screening (sputum only)
- B. cepacia complex within past year or at screening
- Use of intravenous antibiotics or oral quinolones within 14 days of screening
- Investigational drug use within 30 days of screening
- History of alcohol, illicit drug or medication abuse within 1 year of screening
Show all 9Show fewer
- Other major organ dysfunction excluding pancreatic dysfunction
- History of lung transplantation or currently on lung transplant list
- Physical findings at screening that would compromise the safety of the participant or the quality of the study data
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).
Read the detailed description
Life expectancy in CF patients has greatly increased due to improved clinical care. While this is certainly beneficial to CF patients, it has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 remains the primary outcome parameter for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2 %. Therefore, additional parameters are needed that are more sensitive to define abnormalities in CF patients and that can be used in therapeutic trials.
Gas mixing techniques have been shown to be sensitive parameters to define abnormalities in patients with cystic fibrosis, but it is unclear how useful this technique is to detect changes after a therapeutic intervention. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways and can be assessed with the lung clearance index (LCI). Interventions that improve mucous accumulation are expected to improve lung clearance as assessed by this technique. RhDNase has been demonstrated to improve lung function and reduce pulmonary exacerbations in patients with cystic fibrosis due to improved mucus clearance.
Lung clearance index (LCI) has been shown to be more sensitive than spirometry in detecting abnormalities in CF patients. Clear cut-offs have been found which can differentiate normal patients from even newly diagnosed CF patients. However, little is known about how LCI may change with treatment.
- Conditions
- Cystic Fibrosis
- Being tested
- rhDNAse, Placebo
- Keywords
- Pediatrics, Cystic Fibrosis, Lung Clearance Index, rhDNAse
- Medical subject headings
- Cystic Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
rhDNAseDrug
Also called Brand Name: Pulmozyme
2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation.
PlaceboOther
2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation.
| Study group | Role | What they receive |
|---|---|---|
| 1 | Other | This arm will receive the active treatment for 28 days, followed by a 28 day washout period and then the placebo treatment for 28 days. Receives: Drug: rhDNAse; Other: Placebo |
| 2 | Other | This arm will receive the placebo treatment for 28 days, followed by a 28 day washout period and then the active treatment for 28 days. Receives: Drug: rhDNAse; Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Secondary outcomes (7)
Change in FEV1 % predicted
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Change in FVC (in litres)
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Change in FVC % predicted
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Change in FEF25-75 (liters/sec)
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Change in FEF25-75 % predicted
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Change in exhaled nitric oxide concentrations
Measured: The duration of the patient's involvement in the study (approximately 3 months)
Incidence of adverse events and serious adverse events
Measured: Duration of the study (approximately 1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Nov 2007 (estimated)
- Study startJan 2008
- Primary completionJun 2009
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Cystic FibrosisStudies of the same condition, open and under way.
- More trials run by The Hospital for Sick ChildrenThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 17 participants (actual)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Felix Ratjen, The Hospital for Sick Children
- Investigators
- Felix Ratjen, MD, Principal investigator, The Hospital for Sick Children, Toronto Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00557089
- Sponsor's protocol ID
- 1000010903
- Status last verified
- Aug 2013
- First submitted
- 9 Nov 2007
- Last updated
- 2 Sep 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J. 2011 Apr;37(4):806-12. doi: 10.1183/09031936.00072510. Epub 2010 Aug 6.
PubMed 20693248Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.
PubMed 33735508
Study at a glance
From the registry record, last updated by the sponsor on 2 Sep 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized, Placebo-controlled Trial on the Effect of rhDNase on Ventilation Inhomogeneity in Patients With Cystic Fibrosis
- ClinicalTrials.gov ID
- NCT00557089
- Acronym / sponsor ID
- 1000010903
- Conditions
- Cystic Fibrosis
- Keywords
- Pediatrics, Cystic Fibrosis, Lung Clearance Index, rhDNAse
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 17 participants (actual)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Study start
- Jan 2008
- Primary completion
- Jun 2009 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 12 Nov 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will assess whether rhDNase treatment improves ventilation inhomogeneity as assessed by lung clearance index (LCI) in patients with cystic fibrosis (CF).
Detailed description
Life expectancy in CF patients has greatly increased due to improved clinical care. While this is certainly beneficial to CF patients, it has made it more difficult to assess the effect of therapeutic interventions. Currently, FEV1 remains the primary outcome parameter for most clinical trials, but many CF patients have normal pulmonary function and the annual rate of decline is now less than 2 %. Therefore, additional parameters are needed that are more sensitive to define abnormalities in CF patients and that can be used in therapeutic trials.
Gas mixing techniques have been shown to be sensitive parameters to define abnormalities in patients with cystic fibrosis, but it is unclear how useful this technique is to detect changes after a therapeutic intervention. Abnormalities in gas clearance from the lung are largely due to retention of inhaled gases due to mucous obstruction in the lower airways and can be assessed with the lung clearance index (LCI). Interventions that improve mucous accumulation are expected to improve lung clearance as assessed by this technique. RhDNase has been demonstrated to improve lung function and reduce pulmonary exacerbations in patients with cystic fibrosis due to improved mucus clearance.
Lung clearance index (LCI) has been shown to be more sensitive than spirometry in detecting abnormalities in CF patients. Clear cut-offs have been found which can differentiate normal patients from even newly diagnosed CF patients. However, little is known about how LCI may change with treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Other | Drug: rhDNAse, Other: PlaceboThis arm will receive the active treatment for 28 days, followed by a 28 day washout period and then the placebo treatment for 28 days. |
| 2 | Other | Drug: rhDNAse, Other: PlaceboThis arm will receive the placebo treatment for 28 days, followed by a 28 day washout period and then the active treatment for 28 days. |
Who may qualify
- Ages
- 6 to 18 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (7 listed)
- Diagnosis of CF as defined by clinical features of CF and a documented sweat chloride > 60 mEq/L by quantitative pilocarpine iontophoresis test or a genotype showing two well characterized disease causing mutations
- Informed consent and verbal assent (as appropriate) has been provided by the subject's parent or legal guardian and the subject
- 6-18 years of age at enrolment
- Able to perform reproducible spirometry
- Clinically stable at enrolment
Key exclusion criteria (9 listed)
- Respiratory culture positive for:
- Use of intravenous antibiotics or oral quinolones within 14 days of screening
- Investigational drug use within 30 days of screening
- History of alcohol, illicit drug or medication abuse within 1 year of screening
- Other major organ dysfunction excluding pancreatic dysfunction
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| rhDNAseAlso: Brand Name: Pulmozyme2.5 mg rhDNase will be dispensed in 2.5 ml vials and administered once a day for 28 days. Treatment will be administered by inhalation. | Drug | 1, 2 |
| Placebo2.5 mg of the placebo will be dispensed in 2.5 ml vials and administered once a day over 28 days. Treatment will be administered by inhalation. | Other | 1, 2 |
Primary outcome
The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
7 secondary outcomes
Change in FEV1 % predicted
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Change in FVC (in litres)
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Change in FVC % predicted
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Change in FEF25-75 (liters/sec)
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Change in FEF25-75 % predicted
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Change in exhaled nitric oxide concentrations
Time frame: The duration of the patient's involvement in the study (approximately 3 months)
Incidence of adverse events and serious adverse events
Time frame: Duration of the study (approximately 1 year)
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Sep 2013.
- Results publication: PubMed 20693248Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J. 2011 Apr;37(4):806-12. doi: 10.1183/09031936.00072510. Epub 2010 Aug 6.
- Derived from this study: PubMed 33735508Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021 Mar 18;3(3):CD001127. doi: 10.1002/14651858.CD001127.pub5.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Felix Ratjen, MD principal investigator
The Hospital for Sick Children, Toronto Canada
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing rhDNAse in people with Cystic Fibrosis, run by The Hospital for Sick Children at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Sep 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The change in LCI from baseline to end of treatment in rhDnase treated patients versus patients receiving placebo (time frame: The duration of the patient's involvement in the study (approximately 3 months)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00557089, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Sep 2013.