Preliminary Study of Dornase Alpha to Treat Chest Infections Post Lung Transplant.
Patients who have undergone lung transplantation are at an increased risk of developing chest infections due to long-term medication suppressing the immune response. In other chronic lung diseases such as cystic fibrosis (CF) and bronchiectasis, inhaled, nebulised mucolytic medication such as dornase alpha and isotonic saline are often used as part of the management of lung disease characterized by increased or retained secretions. These agents act by making it easier to clear airway secretions, and are currently being used on a case-by-case basis post lung transplantation.
To the investigators knowledge, these agents have not been evaluated via robust scientific investigation when used post lung transplant, yet are widely used in routine practice. Patients post lung transplant must be investigated separately as they exhibit differences in physiology that make the clearance of sputum potentially more difficult when compared to other lung diseases. Lower respiratory tract infections are a leading cause of hospital re-admission post lung transplant. Therefore, this highlights the need for a randomized controlled trial. The aim of this study is to assess the efficacy of dornase alpha, compared to isotonic saline, in the management of lower respiratory tract infections post lung transplant. Investigators hypothesize that dornase alpha will be more effective than isotonic saline.
The effect of a daily dose of dornase alpha and isotonic saline will be compared over a treatment period of 1 month. Patients admitted to hospital suffering from chest infections characterized by sputum production post lung transplant will be eligible for study inclusion. Patients will be followed up through to 3 months in total to analyze short-medium term lasting effect. Investigators wish to monitor physiological change within the lung non-invasively via lung function analysis whilst assessing patient perceived benefit via cough specific quality of life questionnaires. These measures will be taken at study inclusion and repeated after 1 month and 3 months. Day to day monitoring will be performed via patient symptom diaries, incorporating hospital length of stay and exacerbation rate. The outcomes of this study have the potential to guide clinical decision-making and highlight safe and efficacious therapies.
|Lung Transplant Infection Lower Respiratory Tract Infection||Drug: Dornase Alpha Drug: Isotonic Saline.||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Outcomes Assessor
Primary Purpose: Treatment
|Official Title:||Investigating the Role of Nebulised Mucolytic Therapy During Lower Respiratory Tract Infections Post Lung Transplantation.|
- Lung clearance index (LCI) - change [ Time Frame: Study inclusion, 1 month, 3 months ]
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 paediatric 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).
- Regular spirometry (FEV-1, FVC, FEF) - change [ Time Frame: Study inclusion, 1 month, 3 months. ]Pulmonary function testing.
- Leicester Cough Questionnaire (LCQ) - change [ Time Frame: Study inclusion, 1 month, 3 months. ]Cough specific quality of life questionnaire. The LCQ is a 19-question tool, validated in chronic lung disease other than lung transplant(19).
- St. George's Respiratory Questionnaire (SGRQ) - change [ Time Frame: Study inclusion, 1 month, 3 months. ]The SGRQ is a 2-part questionnaire, validated in chronic lung disease other than lung transplant(20).
- Inpatient days [ Time Frame: Across study period (3 months). ]Number of days spent in the acute inpatient setting.
- Oral, inhaled or IVAB days (for LRTI only). [ Time Frame: Over study period (3 months). ]Antibiotic use for the treatment of lower respiratory tract infections only.
- Number of hospitalizations [ Time Frame: Over study period (3 months). ]Number of admissions to the acute setting.
- Exacerbation rate. [ Time Frame: Over study period (3 months). ]
As defined by:
- Presentation to hospital and commencement of antibiotics (oral, inhaled or IV)
- Worsening of symptom scores (Breathlessness, cough and sputum scale >1), sputum colour score (BronkoTest colour 3-5) (*See isolated secondary outcome measures for above).
- C-reactive protein (CRP) - change [ Time Frame: Study inclusion, 1 month, 3 months. ]An inflammatory marker measured with routine blood tests on admission with LRTI. Taken during IP stay and routinely on OP follow-up. Existing / available data only will be used - no extra routine bloods will be taken on account of study inclusion.
- Breathlessness, Cough and Sputum Scale (BCSS) - change [ Time Frame: Daily up to 3 months. ]Self-reported symptom severity, used as a daily patient diary. The BCSS is a 12 point self-reported symptom severity score, validated for daily use in COPD(21).
- BronkoTest (sputum colour) - change [ Time Frame: Daily up to 3 months. ]Sputum colour chart. Sputum colour has been shown to correlate with physiological infection in other chronic lung disease groups(22).
|Study Start Date:||October 2013|
|Estimated Study Completion Date:||September 2017|
|Estimated Primary Completion Date:||June 2017 (Final data collection date for primary outcome measure)|
Experimental: Dornase Alpha
Once daily, 2.5ml inhaled dornase alpha.
Drug: Dornase Alpha
Once daily, 2.5ml inhaled dornase alpha (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.
Other Name: Pulomzyme.
Active Comparator: Isotonic Saline
Once daily, 5ml inhaled 0.9% normal saline.
Drug: 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.
Other Name: normal, 0.9% saline.
Show Detailed Description
Please refer to this study by its ClinicalTrials.gov identifier: NCT01952470
|Melbourne, Victoria, Australia, 3000|
|Contact: Benjamin J Tarrant, Bachelor of Physiotherapy +613 9076 3450 ext pager 5036 firstname.lastname@example.org|
|Contact: Anne E Holland, BApp Sci PhD 0419 379 821 email@example.com|
|Principal Investigator: Benjamin J Tarrant, BPhysio|
|Principal Investigator: Greg I Snell, MbbsFracpMd|
|Sub-Investigator: Anne E Holland, BAppSciPhD|
|Sub-Investigator: Steven P Ivulich, B.Pharm|
|Sub-Investigator: Louise M Fuller, BAppSciPhys|
|Sub-Investigator: Bruce R Thompson, BAppSciPHD|
|Sub-Investigator: Brenda M Button, DipPhys.PhD|
|Principal Investigator:||Benjamin J Tarrant, B.Physio||The Alfred|