Clinical trial NCT04281316: High-Flow in Hypercapnic Stable COPD Patients
Official title: Impact of Nasal High Flow (NHF) Versus Home Non-invasive Ventilation (NIV) on Nocturnal Transcutaneous PCO2 (PtCO2) in Stable COPD Patients: A Non-inferiority Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Adherence, Treatment
Keywords: non-compliance
NIV
NHF
COPD
hypercapnic respiratory failure
Lead sponsor: University Hospital, Grenoble
Sponsor class: OTHER
Collaborators: name: Icadom
name: Fisher and Paykel Healthcare
First posted: 2020-02-24
Enrollment: 3
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Monocentric, prospective, open, randomized 1:1, controlled study to evaluate the impact of nasal high-flow (NHF) on nocturnal transcutaneous PCO2 (PtCO2) compared to non-invasive ventilation ± Long-Term Oxygen Therapy (LTOT) in patients with a Chronic obstructive pulmonary disease (COPD)-related hypercapnic respiratory failure.

Detailed description: Chronic obstructive pulmonary disease (COPD) is a growing global health concern, causing considerable health-related costs and increased mortality. COPD is nowadays considered a complex, heterogeneous and systemic condition.

In the late stage of the disease, non-invasive ventilation (NIV) is widely prescribed either to treat acute hypercapnic respiratory failure during COPD exacerbations or for long term home management.

A meta-analysis has shown that higher daytime PaCO2 occurred in home NIV treated COPD patients when NIV compliance is less than 5 h/day. Thus, an optimal NIV adherence is a key target for controlling nocturnal and diurnal hypoventilation and improving prognosis.

COPD is the clinical scenario during which a good NIV adherence is difficult to achieve. Particularly, in COPDs exhibiting hyperinflation, NIV can aggravate dynamic hyperinflation resulting in unrewarded inspiratory efforts, poor sleep and low NIV compliance. Alternatives to NIV are then desirable in this specific subgroup of hypercapnic COPD with poor adherence to NIV.

During this trial, stable COPD patients treated by long term home Non-Invasive Ventilation (NIV) treatment following French national recommendations and exhibiting a NIV compliance of (less than 5 hours and more than 1 hour) per day in the last 3 months prior to inclusion will be randomized via a secure electronic website to either continue with their current NIV treatment or receive the nasal high flow (NHF) treatment delivered by myAirvo2 during 3 months Nasal High-Flow (NHF) is a treatment delivering heated, humidified, and optionally oxygen-enriched air at high flow rates through a nasal cannula. The main physiologic effects of NHF are an improvement in gas exchanges including a reduction in hypercapnia, an optimization in breathing patterns with a reduction of work of breathing. Nasal High-Flow (NHF) is delivered via a comfortable nasal interface and has demonstrated good treatment adherence.

The investigators hypothesize that in COPD-related hypercapnic chronic respiratory failure with limited compliance to NIV (less than 5 hours per night), nasal High-Flow (NHF) will be non-inferior for controlling nocturnal hypoventilation and might improve daytime subjective patients centered outcomes, physical activity and nocturnal adherence to treatment.

Eligibility criteria: Inclusion Criteria:

* Diagnosed with COPD (FEV1/FVC \< 70%) and long term indication for home NIV for initiated at least 3 months prior the inclusion.
* Compliance with NIV (less than 5 hours and more than 1 hour) per night on average during the last 3 months prior to inclusion.
* Naïve to Nasal High Flow (NHF) therapy, i.e. having not used NHF in the last 6 months prior to inclusion.
* Able to understand, follow objectives and methods of protocol in French language.
* Patient affiliated to social security insurance or beneficiary of social health insurance.
* Willing and able to give written Informed Consent and to comply with the requirements of the study protocol.

Exclusion Criteria:

* Significant uncontrolled cardiac disease (investigator judgment), and/or Left Ventricular Ejection Fraction (LVEF) \< 45%.
* Known co-existing obstructive sleep apnea requiring expiratory pressure above 6 cmH20.
* Severe nasal obstruction, previous upper airway surgery preventing the usage of NHF, or, at the discretion of investigator, any other contraindication for using the NHF.
* Patients who are unable or unwilling to give informed consent.
* Participating in another research study.
* Patient protected by the Law, under guardianship or curators.
* Pregnancy and nursing mothers
* Patient not covered by a health insurance.

Primary outcomes:
measure: Changes on nocturnal parameters with the nasal high-flow (NHF) compared to non-invasive ventilation in patients with a COPD-related hypercapnic respiratory failure.
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
Secondary outcomes:
measure: Evaluation the impact of nasal high-flow (NHF) on other nocturnal parameters compared to non-invasive ventilation ± LTOT compared to non-invasive ventilation in patients with a COPD-related hypercapnic respiratory failure.
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Treatment adherence
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Daytime blood gas values in ambient air
timeFrame: between day 0 (inclusion) and day 97 (end of the study)
measure: Other nocturnal parameter
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Physical activity
timeFrame: for 7 days from the day 1 and for 7 days from the day 90
measure: Sleep activity
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Sleep activity
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Sleep activity
timeFrame: between night at day 1 (baseline) and night at day 90 (3 months after)
measure: Pulmonary function tests
timeFrame: between day 0 and day 97
measure: Pulmonary function tests
timeFrame: between day 0 and day 97
measure: Pulmonary function tests
timeFrame: between day 0 and day 97
measure: Health related quality of life
timeFrame: between day 0 and day 97
measure: Health related quality of life
timeFrame: between day 0 and day 97
measure: Cardiovasculary function
timeFrame: between day 0 and day 97
measure: Number of participants with adverse events will be assessed in each group by interrogating patients in order to assess the safety of nasal high-flow (NHF) treatment
timeFrame: between day 0 and day 97
Other outcomes:
Locations:
city: Grenoble
country: France
facility: Grenoble Alpes University Hospital
Study officials:
affiliation: Laboratoire EFCR, CHU de Grenoble
name: Jean-Louis Pépin, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Biener AI, Decker SL, Rohde F. Prevalence and Treatment of Chronic Obstructive Pulmonary Disease (COPD) in the United States. JAMA. 2019 Aug 20;322(7):602. doi: 10.1001/jama.2019.10241. No abstract available.
citation: Riley CM, Sciurba FC. Diagnosis and Outpatient Management of Chronic Obstructive Pulmonary Disease: A Review. JAMA. 2019 Feb 26;321(8):786-797. doi: 10.1001/jama.2019.0131.
citation: Houben-Wilke S, Augustin IM, Vercoulen JH, van Ranst D, Bij de Vaate E, Wempe JB, Spruit MA, Wouters EFM, Franssen FME. COPD stands for complex obstructive pulmonary disease. Eur Respir Rev. 2018 Jun 6;27(148):180027. doi: 10.1183/16000617.0027-2018. Print 2018 Jun 30.
citation: Suh ES, Murphy PB, Hart N. Home mechanical ventilation for chronic obstructive pulmonary disease: What next after the HOT-HMV trial? Respirology. 2019 Aug;24(8):732-739. doi: 10.1111/resp.13484. Epub 2019 Feb 7.
citation: Crimi C, Noto A, Princi P, Cuvelier A, Masa JF, Simonds A, Elliott MW, Wijkstra P, Windisch W, Nava S. Domiciliary Non-invasive Ventilation in COPD: An International Survey of Indications and Practices. COPD. 2016 Aug;13(4):483-90. doi: 10.3109/15412555.2015.1108960. Epub 2016 Jan 8.
citation: Kohnlein T, Windisch W, Wegscheider K, Welte T. Non-invasive positive pressure ventilation for severe COPD--Authors' reply. Lancet Respir Med. 2014 Oct;2(10):e19. doi: 10.1016/S2213-2600(14)70215-2. No abstract available.
citation: Murphy AM, Thomas A, Crinion SJ, Kent BD, Tambuwala MM, Fabre A, Pepin JL, Roche HM, Arnaud C, Ryan S. Intermittent hypoxia in obstructive sleep apnoea mediates insulin resistance through adipose tissue inflammation. Eur Respir J. 2017 Apr 19;49(4):1601731. doi: 10.1183/13993003.01731-2016. Print 2017 Apr.
citation: Vanfleteren LEGW, Spruit MA, Wouters EFM, Franssen FME. Management of chronic obstructive pulmonary disease beyond the lungs. Lancet Respir Med. 2016 Nov;4(11):911-924. doi: 10.1016/S2213-2600(16)00097-7. Epub 2016 Jun 2.
citation: Borel JC, Pepin JL, Pison C, Vesin A, Gonzalez-Bermejo J, Court-Fortune I, Timsit JF. Long-term adherence with non-invasive ventilation improves prognosis in obese COPD patients. Respirology. 2014 Aug;19(6):857-65. doi: 10.1111/resp.12327. Epub 2014 Jun 9.
citation: Struik FM, Lacasse Y, Goldstein RS, Kerstjens HA, Wijkstra PJ. Nocturnal noninvasive positive pressure ventilation in stable COPD: a systematic review and individual patient data meta-analysis. Respir Med. 2014 Feb;108(2):329-37. doi: 10.1016/j.rmed.2013.10.007. Epub 2013 Oct 14.