Preliminary Study of Dornase Alfa to Treat Chest Infections Post Lung Transplant.

• Status: Completed
• Trial end date: 2017-08-23
• Target enrollment: 0
• Participant gender: All

Summary

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 alfa 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 alfa, compared to isotonic saline, in the management of lower respiratory tract infections post lung transplant. Investigators hypothesize that dornase alfa will be more effective than isotonic saline.

The effect of a daily dose of dornase alfa 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: The Alfred
• Collaborators: Dr Carey Denholm and Laura Denholm; The Alfred Research Trusts Small Project Grant.

Criteria

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

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