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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2013 by The Alfred
Sponsor:
Collaborator:
The Alfred Research Trusts Small Project Grant.
Information provided by (Responsible Party):
Co-Principal Investigator Benjamin Tarrant, The Alfred
ClinicalTrials.gov Identifier:
NCT01952470
First received: August 31, 2013
Last updated: October 30, 2013
Last verified: October 2013
  Purpose

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.


Condition Intervention Phase
Lung Transplant Infection
Lower Respiratory Tract Infection.
Drug: Dornase Alpha
Drug: Isotonic Saline.
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Investigating the Role of Nebulised Mucolytic Therapy During Lower Respiratory Tract Infections Post Lung Transplantation.

Resource links provided by NLM:


Further study details as provided by The Alfred:

Primary Outcome Measures:
  • Lung clearance index (LCI) - change [ Time Frame: Study inclusion, 1 month, 3 months ] [ Designated as safety issue: Yes ]

    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).



Secondary Outcome Measures:
  • Regular spirometry (FEV-1, FVC, FEF) - change [ Time Frame: Study inclusion, 1 month, 3 months. ] [ Designated as safety issue: Yes ]
    Pulmonary function testing.

  • Leicester Cough Questionnaire (LCQ) - change [ Time Frame: Study inclusion, 1 month, 3 months. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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). ] [ Designated as safety issue: No ]
    Number of days spent in the acute inpatient setting.

  • Oral, inhaled or IVAB days (for LRTI only). [ Time Frame: Over study period (3 months). ] [ Designated as safety issue: No ]
    Antibiotic use for the treatment of lower respiratory tract infections only.

  • Number of hospitalizations [ Time Frame: Over study period (3 months). ] [ Designated as safety issue: No ]
    Number of admissions to the acute setting.

  • Exacerbation rate. [ Time Frame: Over study period (3 months). ] [ Designated as safety issue: No ]

    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    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. ] [ Designated as safety issue: No ]
    Sputum colour chart. Sputum colour has been shown to correlate with physiological infection in other chronic lung disease groups(22).


Estimated Enrollment: 30
Study Start Date: October 2013
Estimated Study Completion Date: December 2014
Estimated Primary Completion Date: October 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 / ICU / ventilator dependent
  • Within 2 months of transplant date *Cystic Fibrosis will be stratified
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01952470

Locations
Australia, Victoria
The Alfred Recruiting
Melbourne, Victoria, Australia, 3000
Contact: Benjamin J Tarrant, Bachelor of Physiotherapy    +613 9076 3450 ext pager 5036    b.tarrant@alfred.org.au   
Contact: Anne E Holland, BApp Sci PhD    0419 379 821    a.holland@alfred.org.au   
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         
Sponsors and Collaborators
The Alfred
The Alfred Research Trusts Small Project Grant.
Investigators
Principal Investigator: Benjamin J Tarrant, B.Physio Alfred Health
  More Information

Publications:
Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. The effect of dornase alpha on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J 2011;37:806-812.

Responsible Party: Co-Principal Investigator Benjamin Tarrant, Benjamin James Tarrant, The Alfred
ClinicalTrials.gov Identifier: NCT01952470     History of Changes
Other Study ID Numbers: 342/13
Study First Received: August 31, 2013
Last Updated: October 30, 2013
Health Authority: Australia: Human Research Ethics Committee

Keywords provided by The Alfred:
Lung transplantation
Respiratory Tract Infections
Respiratory Therapy
Isotonic Solutions
Sodium Chloride
Postoperative complications
Postoperative care
dornase alpha

Additional relevant MeSH terms:
Infection
Communicable Diseases
Respiratory Tract Infections
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014