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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT01952470




Registration number
NCT01952470
Ethics application status
Date submitted
31/08/2013
Date registered
30/09/2013

Titles & IDs
Public title
Preliminary Study of Dornase Alfa to Treat Chest Infections Post Lung Transplant.
Scientific title
Investigating the Role of Nebulised Mucolytic Therapy During Lower Respiratory Tract Infections Post Lung Transplantation.
Secondary ID [1] 0 0
DOI:10.1111/tri.13400
Secondary ID [2] 0 0
342/13
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Lung Transplant Infection 0 0
Lower Respiratory Tract Infection 0 0
Condition category
Condition code
Infection 0 0 0 0
Studies of infection and infectious agents
Infection 0 0 0 0
Other infectious diseases
Infection 0 0 0 0
Sexually transmitted infections
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Dornase Alfa
Treatment: Drugs - Isotonic Saline.

Experimental: Dornase Alfa - Once daily, 2.5ml inhaled dornase alfa.

Active comparator: Isotonic Saline - Once daily, 5ml inhaled 0.9% normal saline.


Treatment: Drugs: Dornase Alfa
Once daily, 2.5ml inhaled dornase alfa (evening if able) with inhalational breathing routine (IBR). IBR consists of 4 slow deep breaths followed by 6 relaxed breaths, repeated until nebuliser is complete, coughing when the patient feels the need to expectorate. The patient will be instructed to sit in an upright position with upper limb support as able.

Treatment: Drugs: Isotonic Saline.
Once daily, 5ml inhaled 0.9% normal saline (evening if able) with inhalational breathing routine (IBR). IBR consists of 4 slow deep breaths followed by 6 relaxed breaths, repeated until nebuliser is complete, coughing when the patient feels the need to expectorate. The patient will be instructed to sit in an upright position with upper limb support as able.
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Lung Clearance Index 2% (LCI2%)
Assessment method [1] 0 0
A measure of ventilation inhomogeneity as measured during multiple breath washout (MBW) of inert tracer gases. It has been shown that this test is a potentially more sensitive measure of peripheral airway obstruction than regular spirometry in short term (4 week) mucolytic interventional studies in pediatric Cystic Fibrosis (CF)(17-18). This test would be performed within the respiratory physiology lung function laboratory on site at all assessment points, by an assessor who is blinded to group allocation for follow up data collection. Conventionally used primary endpoints in this population, such as regular spirometry(3), may be unable to detect between group differences without large sample sizes and long treatment durations. Based on current evidence from non-lung transplant populations, LCI has been able to show short-term change, whereas regular spirometry has not shown change(17-18).
Timepoint [1] 0 0
1 month, 3 months
Secondary outcome [1] 0 0
Multiple Breath Washout (MBW)
Assessment method [1] 0 0
Multiple breath washout is a sensitive measure of respiratory function performed with the subject in a seated position, breathing a fixed tidal volume (1L) of inert gas (nitrogen) from functional residual capacity (FRC) via mouthpiece. Two common outcomes of MBW are Sacin, a measure of gas mixing at the diffusion front, or acinar entrance in the airways, and Scond, in the proximal, conductive zones. An increase in either Sacin or Scond represents an increase in ventilation heterogeneity (deterioration). Both increase with age, normal values are non-zero between 0-0.25(Sacin) and 0-0.1(Scond).
Timepoint [1] 0 0
1 month, 3 months
Secondary outcome [2] 0 0
Functional Residual Capacity (FRC)
Assessment method [2] 0 0
Volume of air remaining in the lungs after normal expiration.
Timepoint [2] 0 0
1 month, 3 months
Secondary outcome [3] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Liters
Assessment method [3] 0 0
FEV1 is the maximal amount of air you can forcefully exhale in one second.
Timepoint [3] 0 0
1 month, 3 months.
Secondary outcome [4] 0 0
Forced Expiratory Volume in 1 Second (FEV1) Percent.
Assessment method [4] 0 0
FEV1 is the maximal amount of air you can forcefully exhale in one second.
Timepoint [4] 0 0
1 month, 3 months
Secondary outcome [5] 0 0
Forced Vital Capacity (FVC) Liters
Assessment method [5] 0 0
Forced vital Capacity (FVC) is a measure of the amount of air someone can forcibly expel out of the lungs after taking a breath to fill the lungs as much as possible.
Timepoint [5] 0 0
1 month, 3 months
Secondary outcome [6] 0 0
Forced Vital Capacity (FVC) Percent
Assessment method [6] 0 0
Forced vital Capacity (FVC) is a measure of the amount of air someone can forcibly expel out of the lungs after taking a breath to fill the lungs as much as possible.
Timepoint [6] 0 0
1 month, 3 months
Secondary outcome [7] 0 0
Forced Expiratory Ratio (FER)
Assessment method [7] 0 0
FER represents the proportion of a person's vital capacity that they are able to expire in the first second of forced expiration (FEV1) to the full, forced vital capacity (FVC).
Timepoint [7] 0 0
1 month, 3 months
Secondary outcome [8] 0 0
Leicester Cough Questionnaire (LCQ) - Change
Assessment method [8] 0 0
Cough specific quality of life questionnaire. The LCQ is a 19-question tool, validated in chronic lung disease other than lung transplant(19). Scale 1-7 for physical, psychological, social. Combined score of 3-21 for total. Lower=worse.
Timepoint [8] 0 0
1 month, 3 months.
Secondary outcome [9] 0 0
St. George's Respiratory Questionnaire (SGRQ) - Change
Assessment method [9] 0 0
The SGRQ is a 2-part questionnaire, validated in chronic lung disease other than lung transplant(20). 50 items, 76 weighted responses. Scores range 0-100, higher=worse.
Timepoint [9] 0 0
1 month, 3 months.
Secondary outcome [10] 0 0
Inpatient Days
Assessment method [10] 0 0
Number of days spent in the acute inpatient setting.
Timepoint [10] 0 0
Across study period (3 months).
Secondary outcome [11] 0 0
Oral, Inhaled or Intravenous Antibiotic (IVAB) Days.
Assessment method [11] 0 0
Antibiotic use for the treatment of lower respiratory tract infections (LRTI) only.
Timepoint [11] 0 0
Over study period (3 months).
Secondary outcome [12] 0 0
Number of Hospitalizations
Assessment method [12] 0 0
Number of admissions to the acute setting.
Timepoint [12] 0 0
Over study period (3 months).
Secondary outcome [13] 0 0
C-reactive Protein (CRP)
Assessment method [13] 0 0
An inflammatory marker measured with routine blood tests on admission with LRTI. Taken during inpatient (IP) stay and routinely on outpatient (OP) follow-up. Existing / available data only will be used - no extra routine bloods will be taken on account of study inclusion.
Timepoint [13] 0 0
1 month, 3 months.
Secondary outcome [14] 0 0
Breathlessness, Cough and Sputum Scale (BCSS) - Exacerbations
Assessment method [14] 0 0
Self-reported symptom severity, used as a daily patient diary. The BCSS is a 12 point self-reported symptom severity score, consisting of 3 sections concerning how much difficulty the subject is having with breathing; subjective cough symptoms and trouble caused by sputum, each scoring between 0-4, combining to a total score of 0-12 (higher=worse). This scale is validated for daily use in Chronic Obstructive Pulmonary Disease (COPD)(21). An exacerbation was defined as an increase in BCSS\>1 with =5 days preceding stability.
Timepoint [14] 0 0
Daily up to 3 months.
Secondary outcome [15] 0 0
BronkoTest (Sputum Colour) - Purulent Sputum Days
Assessment method [15] 0 0
Sputum colour chart. Sputum colour has been shown to correlate with physiological infection in other chronic lung disease groups(22).
Timepoint [15] 0 0
Daily up to 3 months.

Eligibility
Key inclusion criteria
* Post bilateral sequential lung transplant
* Capable of performing airway clearance techniques / nebulisers
* Pulmonary exacerbation as defined by Fuchs et al
* Must be productive of sputum
* Able to provide informed consent within 48 hours of presentation.

*Fuchs Scale(8): Treatment with / without parenteral antibiotics for 4/12 signs and symptoms:
* Change in sputum
* New or increased haemoptysis
* Increased cough
* Increased dyspnoea
* Malaise, fever or lethargy
* Temp above 38
* Anorexia or weight loss
* Sinus pain or tenderness
* Change in sinus discharge
* Change in physical examination of the chest
* Radiographic changes indicative of pulmonary infection
* Decrease in pulmonary function by 10 % or more
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Paediatric transplant <18yrs
* Single lung transplant - native lung physiology may confound outcome measures
* Interstate - unable to complete follow up
* Unable to perform lung function testing
* Unable to complete subjective outcome measures- unable to read English fluently
* Critically unwell / intensive care unit / ventilator dependent
* Within 2 months of transplant date *Cystic Fibrosis will be stratified

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2013
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
23/08/2017
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne

Funding & Sponsors
Primary sponsor type
Other
Name
The Alfred
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
The Alfred Research Trusts Small Project Grant.
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Dr Carey Denholm and Laura Denholm
Country [2] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Benjamin J Tarrant, B.Physio
Address 0 0
The Alfred
Country 0 0
Phone 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement


What supporting documents are/will be available?

TypeOther DetailsAttachment
Study protocol Study Protocol and Statistical Analysis Plan
Statistical analysis plan Study Protocol and Statistical Analysis Plan
Informed consent form



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results are available at https://clinicaltrials.gov/study/NCT01952470