Preliminary Study of Dornase Alfa to Treat Chest Infections Post Lung Transplant.
Condition: Lung Transplant Infection; Lower Respiratory Tract Infection
MeSH terms: Infections; Communicable Diseases; Respiratory Tract Infections
Intervention: Dornase Alfa; Isotonic Saline.
Intervention description: 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.; 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.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Enrollment: 32.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Lung transplantation; Respiratory Tract Infections; Respiratory Therapy; Isotonic Solutions; Sodium Chloride; Postoperative complications; Postoperative care; dornase alfa

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.
    

Eligibility 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