The Addition of Non-Invasive Ventilation To Airway Clearance Techniques In Adults With Cystic Fibrosis

Cystic Fibrosis Clinical Trial

— NIV  

Official title:

Non-Invasive Ventilation (NIV) For Positive Pressure Support. A Randomised Cross-Over Trial To Evaluate The Short-Term Effects of NIV As An Adjunct To Airway Clearance Techniques in Adults With Cystic Fibrosis.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01885650
• Other study ID #: 13/LO/0565
• Status: Terminated
• Phase: N/A
• First received: June 17, 2013
• Last updated: August 1, 2017
• Start date: July 2013
• Est. completion date: May 11, 2017

Study information

• Verified date: August 2017
• Source: Royal Brompton & Harefield NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Cystic Fibrosis (CF) is a genetic disorder of altered ion transport across cell membranes which is characterised by the production of thickened bodily secretions, affecting the function of organs such as the pancreas and the lungs. Within the lungs, thickened sputum is very difficult to clear, which can results in recurrent chest infections, which can lead to lung damage. therefore it is important to optimise the removal of sputum to try and prevent these complications. Traditionally, a variety of approaches are usually combined including inhaled medications to thin or hydrate secretions, and chest physiotherapy to mobilise secretions and improve sputum clearance.

There are many chest physiotherapy or airway clearance techniques (ACT) available including breathing methods such as the Active Cycle of Breathing Techniques (ACBT) or Autogenic Drainage (AD) and adjuncts such as Positive Expiratory Pressure (PEP), High Frequency Chest Oscillation (the "Vest"), or oscillatory devices such as the Flutter or Acapella. When people with CF have an infection or have severe disease often the effectiveness of ACTs can decrease due to fatigue, shortness of breath or having an overwhelming amount of sputum. At this time it is necessary to re-assess ACTs and the addition of positive pressure to airway clearance techniques has been shown to be helpful in decreasing fatigue during chest physiotherapy.

At present no research studies have reported an increase in sputum cleared with the addition of positive pressure, however it is thought that the ability to take a deeper breath when using positive pressure would help to improve sputum clearance. With clinical experience of the use of NIV with adult CF patients, the investigators aim to explore this objectively in this study.

Research Question:

Does the addition of non-invasive ventilation (Breas, I-Sleep 25) as supplementary positive pressure to normal airway clearance techniques improve sputum clearance in stable adult patients with cystic fibrosis?

Hypothesis

The inclusion of non-invasive ventilation in addition to a patient's normal airway clearance technique will lead to improvements in subjective ease of clearance and work of breathing during airway clearance and objectively increase sputum clearance, as well as being well tolerated in patients as an adjunct to airway clearance.

Description:

Cystic Fibrosis (CF) is a genetic disorder of altered ion transport across cell membranes which is characterised by the production of thickened bodily secretions, affecting the function of organs such as the pancreas and the lungs. Within the lungs, thickened mucus alters normal mucocillary clearance mechanisms resulting in airway obstruction, mucus plugging and recurrent infections. The cycle of recurrent infections and subsequent inflammation is thought to be the major mechanism towards damage to lung tissue and the occurrence of fibrosis, which decreases lung function, lowers tissue oxygenation and eventually leads to respiratory failure and death. Optimisation of the removal of airway secretions is therefore an integral part of the management of CF in order to try and prevent these complications. Traditionally, a variety of approaches are usually combined including mucolytic or hydrator therapy to make the secretions less viscous, and chest physiotherapy to mobilise secretions and improve airway clearance.

There are many chest physiotherapy or airway clearance techniques (ACT) available including breathing methods such as the Active Cycle of Breathing Techniques (ACBT) or Autogenic Drainage (AD) and adjuncts such as Positive Expiratory Pressure (PEP), High Frequency Chest Oscillation (the "Vest"), or oscillatory devices such as the Flutter or Acapella. Research has shown there to be no difference in effectiveness between techniques, as long as they are performed correctly and regularly, and therefore choice of ACT depends upon assessment of the patient by a trained physiotherapist and discussions with the individual. With advancing disease or infections, often the effectiveness of ACTs can decrease due to patient fatigue, shortness of breath or overwhelming amount of secretions. At this time it is necessary to re-assess ACTs, and the addition of positive pressure to airway clearance techniques has been shown to decrease patient fatigue and respiratory rates during clearance. One of these studies also demonstrated improvements in oxygenation and respiratory muscle strength after the use of positive pressure with ACT. While no studies have reported an increase in sputum expectorated with the addition of positive pressure, the ability to augment greater tidal volumes through positive pressure is thought to be a mechanism which could improve sputum clearance. Clinical experience at the Royal Brompton hospital has indicated that with alterations in pressure and flow rates from resting settings, sputum clearance appears to be easier and more effective; the investigators aim to explore this observation objectively in this study.

Research Question:

Does the addition of non-invasive ventilation (Breas, I-Sleep 25) as supplementary positive pressure to normal airway clearance techniques improve sputum clearance in stable adult patients with cystic fibrosis?

Hypothesis

The inclusion of non-invasive ventilation in addition to a patient's normal airway clearance technique will lead to improvements in subjective ease of clearance and work of breathing during airway clearance and objectively increase sputum clearance, as well as being well tolerated in patients as an adjunct to airway clearance.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 14
• Est. completion date: May 11, 2017
• Est. primary completion date: May 11, 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Diagnosis of cystic fibrosis (confirmed by genotype or a sweat sodium concentration of >70mmol/l or sweat chloride of >60mmol/l)

• Sixteen years of age or over

• Patients admitted to the Royal Brompton Hospital with a pulmonary exacerbation of which is resolving. Patients will be considered for inclusion from day 7 of treatment to 3 days prior to discharge (as determined by a member of the cystic fibrosis medical team and have spirometric values within 20% of the mean of the last two stable recordings (at least 1 month apart)

• Patients with an established airway clearance regime that they have used for 3 months or more

Exclusion Criteria:

• Current moderate haemoptysis (greater than streaking in the sputum)

• Current pneumothorax or history of pneumothorax in the 3 months prior to consideration for the study

• Current dependency on positive pressure support with airway clearance via the IPPB (Intermittent Positive Pressure Breathing) machine or NIV

• Previous history of spontaneous rib fractures

• Pregnancy

• Inability to give consent for treatment or measurement

• Current participation in another study

• If the patient requires more than 2 airway clearance sessions a day

Related Conditions & MeSH terms

• Cystic Fibrosis
• Fibrosis

Intervention

Other:
• Airway Clearance Techniques

Locations

Country	Name	City	State
United Kingdom	The Royal Brompton Hospital	London	Greater London

Sponsors (1)

Lead Sponsor	Collaborator
Royal Brompton & Harefield NHS Foundation Trust

Country where clinical trial is conducted

United Kingdom, 

References & Publications (8)

Cantin A. Cystic fibrosis lung inflammation: early, sustained, and severe. Am J Respir Crit Care Med. 1995 Apr;151(4):939-41. — View Citation

Fauroux B, Boulé M, Lofaso F, Zérah F, Clément A, Harf A, Isabey D. Chest physiotherapy in cystic fibrosis: improved tolerance with nasal pressure support ventilation. Pediatrics. 1999 Mar;103(3):E32. — View Citation

Holland AE, Denehy L, Ntoumenopoulos G, Naughton MT, Wilson JW. Non-invasive ventilation assists chest physiotherapy in adults with acute exacerbations of cystic fibrosis. Thorax. 2003 Oct;58(10):880-4. — View Citation

Konstan MW, Berger M. Current understanding of the inflammatory process in cystic fibrosis: onset and etiology. Pediatr Pulmonol. 1997 Aug;24(2):137-42; discussion 159-61. — View Citation

Osman LP, Roughton M, Hodson ME, Pryor JA. Short-term comparative study of high frequency chest wall oscillation and European airway clearance techniques in patients with cystic fibrosis. Thorax. 2010 Mar;65(3):196-200. doi: 10.1136/thx.2008.111492. Epub 2009 Aug 23. — View Citation

Placidi G, Cornacchia M, Polese G, Zanolla L, Assael BM, Braggion C. Chest physiotherapy with positive airway pressure: a pilot study of short-term effects on sputum clearance in patients with cystic fibrosis and severe airway obstruction. Respir Care. 2006 Oct;51(10):1145-53. — View Citation

Pryor JA, Tannenbaum E, Scott SF, Burgess J, Cramer D, Gyi K, Hodson ME. Beyond postural drainage and percussion: Airway clearance in people with cystic fibrosis. J Cyst Fibros. 2010 May;9(3):187-92. doi: 10.1016/j.jcf.2010.01.004. Epub 2010 Feb 12. — View Citation

Zach MS. Lung disease in cystic fibrosis--an updated concept. Pediatr Pulmonol. 1990;8(3):188-202. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Final Evaluation Questionnaire	A questionnaire designed to look at patient opinion and preferences for treatment methods studied	At the end of each participants study period. These will be completed up to 30 minutes after the final treatment on the final day of the research study.
Primary	Sputum weight (wet) expectorated during, up to 30 minutes after treatment and the 24 hour total weight	The amount of sputum expectorated by the patient both up to 30 minutes after treatment, and the total amount cleared in 24 hours after each treatment	24 hours
Secondary	Qualitative assessment using 10 centimetre Visual Analogue Scale (VAS) of ease of clearance, work of breathing during clearance and satisfaction of each treatment approach (A or B).		Within 5 minutes immediately after each treatment
Secondary	Lung function tests	Forced Expiratory Volume in 1 second (FEV1) Forced Vital Capacity (FVC) Forced Expiratory Flow at 25% of FVC (FEF25) Forced Expiratory Flow at 75% of FVC (FEF75)	5 minutes before treatment, within 5 minutes immediately after treatment and 30 minutes after treatment
Secondary	Oxygen saturations during the treatment session	Measurements of oxygen saturations via finger probe pulse oximetry	During the treatment