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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]

DOI:10.1111/tri.13400

Secondary ID [2]

342/13

Universal Trial Number (UTN)

Trial acronym

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Lung Transplant Infection

Lower Respiratory Tract Infection

Condition category

Condition code

Infection

Studies of infection and infectious agents

Infection

Other infectious diseases

Infection

Sexually transmitted infections

Respiratory

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]

Treatment: Drugs

Comparator / control treatment

Control group

Outcomes

Primary outcome [1]

Lung Clearance Index 2% (LCI2%)

Timepoint [1]

1 month, 3 months

Secondary outcome [1]

Multiple Breath Washout (MBW)

Timepoint [1]

1 month, 3 months

Secondary outcome [2]

Functional Residual Capacity (FRC)

Timepoint [2]

1 month, 3 months

Secondary outcome [3]

Forced Expiratory Volume in 1 Second (FEV1) Liters

Timepoint [3]

1 month, 3 months.

Secondary outcome [4]

Forced Expiratory Volume in 1 Second (FEV1) Percent.

Timepoint [4]

1 month, 3 months

Secondary outcome [5]

Forced Vital Capacity (FVC) Liters

Timepoint [5]

1 month, 3 months

Secondary outcome [6]

Forced Vital Capacity (FVC) Percent

Timepoint [6]

1 month, 3 months

Secondary outcome [7]

Forced Expiratory Ratio (FER)

Timepoint [7]

1 month, 3 months

Secondary outcome [8]

Leicester Cough Questionnaire (LCQ) - Change

Timepoint [8]

1 month, 3 months.

Secondary outcome [9]

St. George's Respiratory Questionnaire (SGRQ) - Change

Timepoint [9]

1 month, 3 months.

Secondary outcome [10]

Inpatient Days

Timepoint [10]

Across study period (3 months).

Secondary outcome [11]

Oral, Inhaled or Intravenous Antibiotic (IVAB) Days.

Timepoint [11]

Over study period (3 months).

Secondary outcome [12]

Number of Hospitalizations

Timepoint [12]

Over study period (3 months).

Secondary outcome [13]

C-reactive Protein (CRP)

Timepoint [13]

1 month, 3 months.

Secondary outcome [14]

Breathlessness, Cough and Sputum Scale (BCSS) - Exacerbations

Timepoint [14]

Daily up to 3 months.

Secondary outcome [15]

BronkoTest (Sputum Colour) - Purulent Sputum Days

Timepoint [15]

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?

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

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment hospital [1]

The Alfred - Melbourne

Recruitment postcode(s) [1]

3000 - Melbourne

Funding & Sponsors

Primary sponsor type

Other

Name

The Alfred

Address

Country

Other collaborator category [1]

Other

Name [1]

The Alfred Research Trusts Small Project Grant.

Address [1]

Country [1]

Other collaborator category [2]

Other

Name [2]

Dr Carey Denholm and Laura Denholm

Address [2]

Country [2]

Ethics approval

Ethics application status

Summary

Brief 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.

Trial website

https://clinicaltrials.gov/study/NCT01952470

Trial related presentations / publications

Hertz MI. The Registry of the International Society for Heart and Lung Transplantation--Introduction to the 2012 annual reports: new leadership, same vision. J Heart Lung Transplant. 2012 Oct;31(10):1045-51. doi: 10.1016/j.healun.2012.08.003. No abstract available. Erratum In: J Heart Lung Transplant. 2013 Feb;32(2):275.
Herve P, Silbert D, Cerrina J, Simonneau G, Dartevelle P. Impairment of bronchial mucociliary clearance in long-term survivors of heart/lung and double-lung transplantation. The Paris-Sud Lung Transplant Group. Chest. 1993 Jan;103(1):59-63. doi: 10.1378/chest.103.1.59.
Munro PE, Button BM, Bailey M, Whitford H, Ellis SJ, Snell GI. Should lung transplant recipients routinely perform airway clearance techniques? A randomized trial. Respirology. 2008 Nov;13(7):1053-60. doi: 10.1111/j.1440-1843.2008.01386.x. Epub 2008 Aug 18.
Veale D, Glasper PN, Gascoigne A, Dark JH, Gibson GJ, Corris PA. Ciliary beat frequency in transplanted lungs. Thorax. 1993 Jun;48(6):629-31. doi: 10.1136/thx.48.6.629.
Humplik BI, Sandrock D, Aurisch R, Richter WS, Ewert R, Munz DL. Scintigraphic results in patients with lung transplants: a prospective comparative study. Nuklearmedizin. 2005 Apr;44(2):62-8. doi: 10.1267/nukl05020062.
Higenbottam T, Jackson M, Woolman P, Lowry R, Wallwork J. The cough response to ultrasonically nebulized distilled water in heart-lung transplantation patients. Am Rev Respir Dis. 1989 Jul;140(1):58-61. doi: 10.1164/ajrccm/140.1.58.
Fuchs HJ, Borowitz DS, Christiansen DH, Morris EM, Nash ML, Ramsey BW, Rosenstein BJ, Smith AL, Wohl ME. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994 Sep 8;331(10):637-42. doi: 10.1056/NEJM199409083311003.
Touleimat BA, Conoscenti CS, Fine JM. Recombinant human DNase in management of lobar atelectasis due to retained secretions. Thorax. 1995 Dec;50(12):1319-21; discussion 1323. doi: 10.1136/thx.50.12.1319.
Voelker KG, Chetty KG, Mahutte CK. Resolution of recurrent atelectasis in spinal cord injury patients with administration of recombinant human DNase. Intensive Care Med. 1996 Jun;22(6):582-4. doi: 10.1007/BF01708100.
Riethmueller J, Borth-Bruhns T, Kumpf M, Vonthein R, Wiskirchen J, Stern M, Hofbeck M, Baden W. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol. 2006 Jan;41(1):61-6. doi: 10.1002/ppul.20298. Erratum In: Pediatr Pulmonol. 2006 Apr;41(4):388.
Crockett AJ, Cranston JM, Latimer KM, Alpers JH. Mucolytics for bronchiectasis. Cochrane Database Syst Rev. 2000;(2):CD001289. doi: 10.1002/14651858.CD001289.
Wark P, McDonald VM. Nebulised hypertonic saline for cystic fibrosis. Cochrane Database Syst Rev. 2009 Apr 15;(2):CD001506. doi: 10.1002/14651858.CD001506.pub3.
Elkins MR, Robinson M, Rose BR, Harbour C, Moriarty CP, Marks GB, Belousova EG, Xuan W, Bye PT; National Hypertonic Saline in Cystic Fibrosis (NHSCF) Study Group. A controlled trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. N Engl J Med. 2006 Jan 19;354(3):229-40. doi: 10.1056/NEJMoa043900.
Nicolson CH, Stirling RG, Borg BM, Button BM, Wilson JW, Holland AE. The long term effect of inhaled hypertonic saline 6% in non-cystic fibrosis bronchiectasis. Respir Med. 2012 May;106(5):661-7. doi: 10.1016/j.rmed.2011.12.021. Epub 2012 Feb 19.
Safdar A, Shelburne SA, Evans SE, Dickey BF. Inhaled therapeutics for prevention and treatment of pneumonia. Expert Opin Drug Saf. 2009 Jul;8(4):435-49. doi: 10.1517/14740330903036083.
Amin R, Subbarao P, Lou W, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. The effect of dornase alfa on ventilation inhomogeneity in patients with cystic fibrosis. Eur Respir J. 2011 Apr;37(4):806-12. doi: 10.1183/09031936.00072510. Epub 2010 Aug 6.
Amin R, Subbarao P, Jabar A, Balkovec S, Jensen R, Kerrigan S, Gustafsson P, Ratjen F. Hypertonic saline improves the LCI in paediatric patients with CF with normal lung function. Thorax. 2010 May;65(5):379-83. doi: 10.1136/thx.2009.125831.
Raj AA, Pavord DI, Birring SS. Clinical cough IV:what is the minimal important difference for the Leicester Cough Questionnaire? Handb Exp Pharmacol. 2009;(187):311-20. doi: 10.1007/978-3-540-79842-2_16.
Jones PW. Interpreting thresholds for a clinically significant change in health status in asthma and COPD. Eur Respir J. 2002 Mar;19(3):398-404. doi: 10.1183/09031936.02.00063702.
Leidy NK, Rennard SI, Schmier J, Jones MK, Goldman M. The breathlessness, cough, and sputum scale: the development of empirically based guidelines for interpretation. Chest. 2003 Dec;124(6):2182-91. doi: 10.1378/chest.124.6.2182.
Stockley RA, Bayley D, Hill SL, Hill AT, Crooks S, Campbell EJ. Assessment of airway neutrophils by sputum colour: correlation with airways inflammation. Thorax. 2001 May;56(5):366-72. doi: 10.1136/thorax.56.5.366.

Public notes

Contacts

Principal investigator

Name

Benjamin J Tarrant, B.Physio

Address

The Alfred

Country

Phone

Fax

Contact person for public queries

Name

Address

Country

Phone

Fax

Contact person for scientific queries

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

No/undecided IPD sharing reason/comment

What supporting documents are/will be available?

Type	Other Details	Attachment
Study protocol	Study Protocol and Statistical Analysis Plan	https://cdn.clinicaltrials.gov/large-docs/70/NCT01952470/Prot_SAP_000.pdf
Statistical analysis plan	Study Protocol and Statistical Analysis Plan	https://cdn.clinicaltrials.gov/large-docs/70/NCT01952470/Prot_SAP_000.pdf
Informed consent form		https://cdn.clinicaltrials.gov/large-docs/70/NCT01952470/ICF_001.pdf

Results publications and other study-related documents

No documents have been uploaded by study researchers.

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

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Registering a new trial?

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