Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001701415
Ethics application status
Approved
Date submitted
6/12/2016
Date registered
12/12/2016
Date last updated
13/12/2017
Type of registration
Prospectively registered

Titles & IDs
Public title
Comparing the effect of Nasal High Flow (NHF) therapy with Non-invasive ventilation (NIV) on carbon dioxide levels in Chronic Obstructive Pulmonary Disease (COPD) patients with chronic respiratory failure
Scientific title
Comparing the effect of Nasal High Flow (NHF) therapy with Non-invasive ventilation (NIV) on PaCO2 in COPD patients with chronic respiratory failure
Secondary ID [1] 286885 0
Nil
Universal Trial Number (UTN)
U1111-1188-6144
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Chronic Obstructive Pulmonary Disease (COPD) 295294 0
Condition category
Condition code
Respiratory 295554 295554 0 0
Chronic obstructive pulmonary disease

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nasal high flow (NHF) therapy, via the myAIRVO 2 device at 45 Litres per minute, 37 degrees for 60 minutes at the Medical Research Institute of New Zealand Respiratory Physiology Lab. This involves breathing heated and humidified room air (and oxygen if required) through the nasal interface (nasal prongs which sit inside both nostrils). Oxygen, if required, will be administered through the device and titrated by the investigator to maintain saturations 88-92%.

There will be a 30 minute wash-in period before starting Intervention 1 where oxygen will be administered, if required, and titrated by the investigator to maintain saturations of 88-92%. The oxygen flow at the end of this wash-in will be used at the start of Intervention 1.

There will be a 15 minute washout period between interventions and recordings will continue during this time. The washout will be extended until the PtCO2 returns to within 4mmHg of t=0 recording of intervention 1.
Intervention code [1] 296329 0
Treatment: Devices
Intervention code [2] 296585 0
Treatment: Other
Comparator / control treatment
Non-invasive ventilation, via Bi-level Positive Airways Pressure at 15cmH2O inspiratory positive airways pressure (IPAP) and 4 cmH2O expiratory positive airways pressure, for 60 minutes at the Medical Research Institute of New Zealand Respiratory Physiology Lab . This involves breathing room air (and oxygen if required) through the mask interface. Oxygen, if required, will be administered through the device and titrated by the investigator to maintain saturations 88-92%. IPAP setting may be altered, down to a minimum of 10cmH2O if not tolerable at 15 cmH2O.
Control group
Active

Outcomes
Primary outcome [1] 300094 0
Transcutaneous partial pressure of carbon dioxide (PtCO2) at 60 minutes adjusted for baseline. Nb: Baseline is the measurement taken at t=0 at the start of each intervention. Intervention number 2 will have a baseline +/- 4mmHg from baseline for Intervention 1. This will be measured on a Sentec transcutaneous monitor.
Timepoint [1] 300094 0
60 minutes
Secondary outcome [1] 329003 0
PtCO2 at 5 minute intervals during the intervention, adjusted for baseline. Note: Baseline is the measurement taken at t=0 at the start of each intervention. Intervention number 2 will have a baseline +/- 4mmHg from baseline for Intervention 1. This will be measured on a Sentec transcutaneous monitor.
Timepoint [1] 329003 0
5 minute intervals (t=5, t=10, t=15 up to t=60) and at the end of the subsequent 15 minute washout period.
Secondary outcome [2] 329004 0
The proportion of patients that have a decrease in PtCO2 by greater than or equal to 4mmHg compared to baseline. This will be measured on a Sentec transcutaneous monitor.
Note: Baseline is the measurement taken at t=0 at the start of each intervention. Intervention 2 will have a baseline +/- 4mmHg from baseline for Intervention 1.
Timepoint [2] 329004 0
60 minutes
Secondary outcome [3] 329005 0
Oxygen saturation at 5 minute intervals during the intervention, adjusted for baseline*.
* Baseline is the measurement taken at t=0 at the start of each intervention. Intervention number 2 will have a baseline +/- 4mmHg from baseline for Intervention 1. This will be measured on a Sentec transcutaneous monitor.
Timepoint [3] 329005 0
5 minute intervals (t=5, t=10, t=15 up to and including t=60) and at the end of the subsequent 15 minute washout period.
Secondary outcome [4] 329006 0
Heart rate at 5 minute intervals during the intervention, adjusted for baseline*.
* Baseline is the measurement taken at t=0 at the start of each intervention. Intervention number 2 will have a baseline +/- 4mmHg from baseline for Intervention 1. This will be measured on a Sentec transcutaneous monitor.
Timepoint [4] 329006 0
5 minute intervals (t=5, t=10, t=15 up to and including t=60) and at the end of the subsequent 15 minute washout period.
Secondary outcome [5] 329007 0
Respiratory rate at 5 minute intervals during the intervention, adjusted for baseline*.
* Baseline is the measurement taken at t=0 at the start of each intervention. Intervention number 2 will have a baseline +/- 4mmHg from baseline for Intervention 1. This will be counted by the Unblinded investigator over the preceding 1 minute before each 5 minute time-point.
Timepoint [5] 329007 0
5 minute intervals (t=5, t=10, t=15 up to and including t=60) and at the end of the subsequent 15 minute washout period.
Secondary outcome [6] 329008 0
Proportion of participants who withdrew from the interventions before completion.
Timepoint [6] 329008 0
60 minutes
Secondary outcome [7] 329009 0
Tolerability questionnaire (designed for the study) results
Timepoint [7] 329009 0
Tolerability questionnaires will be administered at the end of each intervention in the washout period.
Secondary outcome [8] 329010 0
BORG dyspnoea score results
Timepoint [8] 329010 0
BORG dyspnoea score will be measured immediately prior and immediately after each intervention.
Secondary outcome [9] 329955 0
The proportion of patients that have a decrease in PtCO2 by greater than or equal to 8mmHg compared to baseline. This will be measured on a Sentec transcutaneous monitor.
Note: Baseline is the measurement taken at t=0 at the start of each intervention. Intervention 2 will have a baseline +/- 4mmHg from baseline for Intervention 1.
Timepoint [9] 329955 0
60 minutes

Eligibility
Key inclusion criteria
1. A doctor’s diagnosis of COPD
2. PcapCO2 >45mmHg on Capillary blood gas, at point of randomisation
3. Age greater than or equal to 40 years old.
Minimum age
40 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Smoking pack year history <10 years
2. FEV1/FVC greater than or equal to 70%
3. Body mass index >35
4. Hypercapnea believed to be primarily due to Obesity Hypoventilation syndrome and/or Obstructive Sleep Apnoea
5. Any condition which makes NIV contra-indicated as per BTS guidelines.
6. Requiring greater than or equal to 4 L/min through standard nasal cannulae during the wash-in period to maintain oxygen saturations 88-92%.
7. COPD not deemed to be ‘stable’:
a. Current exacerbation requiring acute treatment with a short course of antibiotics/oral steroids within the last 2 weeks.
b. Hospital admission for an acute exacerbation of COPD in the last 6 weeks.
8. Nasal conditions such as deviated septum, chronic rhinitis, current cold/flu which, in the evaluation by the investigator, could impair nasal breathing.
9. Any other condition, which at the investigator’s discretion, is believed may present a safety risk or impact the feasibility of the study or study results.

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)
Participants will be considered enrolled and part of the study population at the time the Consent Form has been filled in by both the Participant and Study Investigator. The Blinded Investigator responsible for documenting PtCO2, heart rate and oxygen saturations, will be blinded to which intervention the participant is receiving by a screen. A second Unblinded Investigator will be responsible for opening an opaque envelope containing the randomised treatment, applying, administering the randomised treatment, recording respiratory rate and administering the questionnaires. The participant will not be told the order they receive the different interventions. We will ask them not to divulge any detected differences in flow to the investigators due to risk of un-blinding the Blinded Investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation code will be pre-generated by the study statistician
by computer and stored in a sealed opaque envelope which will be
opened by the Un-Blinded Investigator at randomisation (immediately
prior to the first intervention).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
Intervention assignment
Crossover
Other design features
Randomised controlled 2-way crossover trial. Two investigators will carry out each study visit: one of these will be blinded to the treatment allocation and one unblinded. Participants will not be told in which order they will receive the interventions.
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
The sample size of 24 has 80% power, type I error rate 5%, to detect a difference of 2.4 mmHg. This is half the difference found in a study of participants with obesity hypoventilation syndrome which reported a mean (standard deviation) paired difference of 5 (4) mmHg (Wijesinghe et al, CHEST 2011; 139(5):1018–1024).

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
14/12/2016
Actual
26/01/2017
Date of last participant enrolment
Anticipated
21/06/2017
Actual
21/09/2017
Date of last data collection
Anticipated
21/06/2017
Actual
21/09/2017
Sample size
Target
24
Accrual to date
Final
24
Recruitment outside Australia
Country [1] 8375 0
New Zealand
State/province [1] 8375 0
Wellington

Funding & Sponsors
Funding source category [1] 294891 0
Government body
Name [1] 294891 0
Health Research Council of New Zealand
Country [1] 294891 0
New Zealand
Funding source category [2] 294892 0
Charities/Societies/Foundations
Name [2] 294892 0
Medical Research Institute of New Zealand
Country [2] 294892 0
New Zealand
Primary sponsor type
Charities/Societies/Foundations
Name
Medical Research Institute of New Zealand
Address
Level 7 CSB
Wellington Regional Hospital
Riddiford Street
Newtown
Wellington 6021
Country
New Zealand
Secondary sponsor category [1] 293728 0
None
Name [1] 293728 0
Address [1] 293728 0
Country [1] 293728 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296270 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 296270 0
Ministry of Health
133 Molesworth Street
PO Box 5013
Wellington
6011
Ethics committee country [1] 296270 0
New Zealand
Date submitted for ethics approval [1] 296270 0
27/10/2016
Approval date [1] 296270 0
04/11/2016
Ethics approval number [1] 296270 0
16/NTB/207

Summary
Brief summary
This study will compare the effect of Nasal High Flow therapy and Non-invasive ventilation on the blood levels of carbon dioxide (PaCO2) in participants with chronic respiratory failure associated with stable chronic obstructive pulmonary disease (COPD). Acute exacerbations of this condition cause a build-up of carbon dioxide in the blood which can require ventilation and increase risk of death. Acute exacerbations of COPD lead to 12000 hospital admissions in New Zealand every year. NHF therapy has a potential role in lowering carbon dioxide levels in COPD patients and we therefore wish to study the effects further and compare it to the gold standard of NIV. Participants will undergo an informed consent process, gathering of personal/medical information and lung function testing. They will then be randomised to the order they receive the 2 interventions for 60 minutes at a time and a ‘washout’ period of 15 minutes after each. There will be a 30 minute 'wash in' period whereby supplemental oxygen will be given, if required, to maintain oxygen saturations of 88-92%. This oxygen flow will be used at the start of intervention 1 and continuously titrated through either the NHF or NIV to maintain oxygen saturations of 88-92%. The participant will be asked to complete a tolerability questionnaire following each 60 minute intervention. and will be asked about their breathlessness, on the BORG dyspnoea score, before and after each intervention..
The primary aim of the study is to identify whether the NHF device has an equivalent impact on PaCO2 levels, compared to NIV in participants. Secondary outcomes include how well participants tolerate the 2 devices and other physical parameters such as respiratory rate, oxygen saturations,and heart rate.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 57970 0
Dr James Fingleton
Address 57970 0
Medical Research Institute of New Zealand Level 7 CSB Wellington
Regional Hospital Riddiford Street Newtown Wellington 6021
Country 57970 0
New Zealand
Phone 57970 0
+64 4 805 0247
Fax 57970 0
Email 57970 0
[email protected]
Contact person for public queries
Name 57971 0
Dr Steven McKinstry
Address 57971 0
Medical Research Institute of New Zealand Level 7 CSB Wellington
Regional Hospital Riddiford Street Newtown Wellington 6021
Country 57971 0
New Zealand
Phone 57971 0
+64 4 805 0261
Fax 57971 0
Email 57971 0
[email protected]
Contact person for scientific queries
Name 57972 0
Dr Steven McKinstry
Address 57972 0
Medical Research Institute of New Zealand Level 7 CSB Wellington
Regional Hospital Riddiford Street Newtown Wellington 6021
Country 57972 0
New Zealand
Phone 57972 0
+64 4 805 0261
Fax 57972 0
Email 57972 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseNasal high-flow therapy compared with non-invasive ventilation in COPD patients with chronic respiratory failure: A randomized controlled cross-over trial.2019https://dx.doi.org/10.1111/resp.13575
N.B. These documents automatically identified may not have been verified by the study sponsor.