High Flow Nasal Oxygen for Exacerbation COPD

Study Overview
=================
Brief Summary
-----------------
In this pilot study the feasibility of performing a larger trial to study the non-inferiority of High Flow Nasal Oxygen compared to non-invasive ventilation in patients with acute acidotic hypercapnic exacerbation of COPD wil be investigated

Detailed Description
-----------------
Rationale: Chronic Obstructive Pulmonary Disease (COPD) is frequently complicated by a worsening of symptoms, known as acute exacerbations (AECOPD). These exacerbations can result in a life-threatening condition with an impaired gas exchange, resulting in hypercapnia and as a result respiratory acidosis. The current standard of care of respiratory support for these patients is non-invasive ventilation (NIV), which has been shown to reduce morbidity and mortality. However, NIV is often unsuccessful, due to intolerance, agitation or patient-ventilation dyssynchrony. Furthermore, NIV is a resource-intensive therapy. High flow nasal oxygen (HFNO) is a non-invasive respiratory support mode that provides heated and humidified gas through soft nasal prongs. Several studies have shown that HFNO improves gas exchange and reduces work of breathing in non-hypercapnic respiratory failure. Furthermore, HFNO is thought to be better tolerated than NIV and the nursing effort may be lower compared to NIV. The hypothesis is that HFNO is non-inferior to NIV for patients with acidotic, hypercapnic AECOPD regarding the need for intubation and mortality, and that it increases patient comfort and reduces nursing effort. Objective: To assess the feasibility of a larger study comparing HFNO with NIV as first line treatment in hypercapnic, acidotic AECOPD. Study design: prospective, randomized, multi-center, unblinded, pilot study. Study population: Patients with acidotic, hypercapnic AECOPD Intervention (if applicable): HFNO versus NIV as first line treatment at presentation Main study parameters/endpoints: Feasibility: screening rate, inclusion rate, feasibility as qualified by staff and nurses. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: All participating patients will receive standard of care (i.e., admission to the monitored ward or ICU for intensive monitoring and regular blood withdrawals, steroids, bronchodilator inhalation therapy). There will be one extra questionnaire after 3 months, but no extra blood samples or site visits, compared to regular care for the participating patients. Permission of the patient will be obtained to register date of hospital discharge and outcome after ICU discharge and ask them to fill out questionnaires at 3 months after admission about their quality of life. Previous studies have not shown that HFNO is inferior to NIV with regards to outcomes (intubation rate, mortality), albeit that they were not powered to prove non-inferiority.

Official Title
-----------------
High Flow Nasal Oxygen For Hypercapnic, Acidotic Exacerbation Chronic Obstructive Pulmonary Disease

Conditions
-----------------
Acute Exacerbation of COPD

Intervention / Treatment
-----------------
* Other: HFNO
* Other: NIV


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Known chronic obstructive pulmonary disease Acute hypercapnic exacerbation of this condition, defined as: PaCO2>45 mmHg or >6.0 kPa and pH 7.20-7.35 Age >40 years Exclusion Criteria: Asthma Immediate need for intubation, based on clinical judgement of the attending physician. Impossibility to apply either one of the two interventions Patient not expected to give immediate or delayed informed consent (e.g. known cognitive impairment, dementia, active serious psychiatric disease, mental retardation). Established home-NIV or home CPAP, known indication for home-NIV or CPAP (e.g. OSAS or obesitas hypoventilation syndrome). Impeding death Concurrent (respiratory) diseases that may influence treatment efficacy: acute heart infarction, cardiogenic lung edema, massive pulmonary embolism (intermediate-high risk or more). NB; pulmonary infections (viral and bacterial) are a common cause of exacerbation and are no reason for exclusion. Other acute diseases that preclude participation in the trial such as hemodynamic instability (need for vasopressors), reduced consciousness with need for intubation, severe intoxication Tracheostomized patients Participation in other interventional trials Impossibility to admit the patient to the participating ICU or monitored ward (e.g. medium care / high dependency unit, depending on local infrastructure). Previous explicit (or written) objection to participation in research

Ages Eligible for Study
-----------------
Minimum Age: 40 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: pilot randomized unblinded controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: High Flow Nasal Oxygen (HFNO)<br>Patients will start at a flow of 50 L/min and a temperature of 37°C, FiO2¬ will start at 25%, and titrated to target SpO2 (88-92%, as in usual care). | Other: HFNO<br>* Respiratory support with HFNO (as opposed to NIV, as per standard of care)<br>|
| Active Comparator: Non-Invasive Ventilation (NIV)<br>Patients will be started at Using the facemask interface: EPAP/PEEP set at 5-7 cmH2O and PS of 5-7 cmH2O (equal to IPAP of 10-14 cmH2O). Using the helmet interface; EPAP/PEEP set at least 10 cmH2O and PS of 10 cmH2O (equal to IPAP of 20 cmH2O). PEEP/EPAP and IPAP/PS can be titrated to effectiveness, tolerance and comfort FiO2 should be set to achieve a SpO2 of 88-92% | Other: NIV<br>* Respiratory support with Non-invasive ventilation, standard of care<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| feasilibity to perform a larger RCT | Inclusion rate | 1 year | 
| feasibility to perform a larger RCT | Screening rate | 1 year | 
| feasibility to perform a larger RCT | perceived feasibility as qualified by staff and nurses | 1 year | 
| feasibility to perform a larger RCT | protocol deviations | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment failure | cross-over, invasive mechanical ventilation, death | 30 days | 
| duration of intervention | time of respiratory support | 30 days | 
| need for sedation | use of sedatives | up to 48 hours or untill end of ICU admission | 
| heart rate | beats per minute | at start, 1, 2, 6, 12, 24 and 48 hours | 
| respiratory rate | breaths per minute | at start, 1, 2, 6, 12, 24 and 48 hours | 
| blood pressure | systolic and diastolic pressure in mmHg | at start, 1, 2, 6, 12, 24 and 48 hours | 
| SpO2 | peripheral saturation by pulsoxymeter (in %) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| blood gas | with pH, PO2, PCO2, bicarbonate | at start, 1, 2, 6, 12, 24 and 48 hours | 
| dyspnea score | Borg dyspnea score (0-10 on VAS) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| Clinical Parameters | heart rate, respiratory rate, blood pressure, Spo2, arterial blood gas, dyspnea score, glasgow coma scale, RASS, seceretions | at start, 1, 2, 6, 12, 24 and 48 hours | 
| consciousness | glasgow coma scale (EMV) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| agitation and sedation level | Richmond Agitation and Sedation scale (RASS) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| secretions | (as 0 (absent), 1 (low quantity), 2 (intermediate), 3 (abundant), or 4 (very abundant) little to normal/abundant) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| HFNO ventilatory support parameters flow | flow in L/min | at start, 1, 2, 6, 12, 24 and 48 hours | 
| HFNO ventilatory support parameters FiO2 | FiO2 in % | at start, 1, 2, 6, 12, 24 and 48 hours | 
| HFNO ventilatory support parameters temperature | temperature in Celcius | at start, 1, 2, 6, 12, 24 and 48 hours | 
| NIV ventilatory support parameters PEEP | PEEP in cmH2O | at start, 1, 2, 6, 12, 24 and 48 hours | 
| NIV ventilatory support parameters PS | PS in cmH2O | at start, 1, 2, 6, 12, 24 and 48 hours | 
| NIV ventilatory support parameters: FiO2 | FiO2 in % | at start, 1, 2, 6, 12, 24 and 48 hours | 
| (dys)comfort score | 10 point VAS scale | at start, 1, 2, 6, 12, 24 and 48 hours | 
| HACOR score | calculated from abovementioned parameters (pH, conciousness, PaO2/Fio2, respiratory rate) | at start, 1, 2, 6, 12, 24 and 48 hours | 
| facial pressure sores | scored daily: yes or no | untill ICU discharge, which is usually up to 1 week | 
| nursing effort | respiratory support interventions per 2 hour | first 6 hours of study | 
| 30d mortality | mortality | 30 days | 
| 90d mortality | mortality | 90 days | 
| 90d quality of life EQ5D | EQ5D | 90 days | 
| 90d quality of life SF36 | SF-36 | 90 days | 
| 90d anxiety and depression | HADS | 90 days | 
| 90d PTDS | IES-R | 90 days | 
| 90d PTSD | IES-R | 90 days | 
| 90d dyspnea CCQ | CCQ | 90 days | 
| 90d dyspnea MRC | MRC | 90 days |