High Flow Nasal Oxygen for Exacerbation COPD (HiCAP)

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

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

Study Overview

• Status: Recruiting
• Conditions: Acute Exacerbation of COPD
• Intervention / Treatment: Other: HFNO; Other: NIV

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.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Dorien Kiers, MD, PhD; Phone Number: +3110 461 6161; Email: d.kiers@franciscus.nl

Study Locations

• Netherlands
  • Delft, Netherlands
    • Not yet recruiting
    • Reinier de Graaf
    • Contact: Louise Urlings, MD, PhD
  • Den Haag, Netherlands
    • Not yet recruiting
    • Haaglanden Medisch Centrum
    • Contact: Peter van Vliet, MD, PhD
  • Rotterdam, Netherlands
    • Recruiting
    • Franciscus Gasthuis & Vlietland
    • Contact: Doiren Kiers, MD, PhD
  • Rotterdam, Netherlands
    • Not yet recruiting
    • Ikazia
    • Contact: Susanne Stads, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 - bicarbonate <20 mmol/L

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Flow Nasal Oxygen (HFNO); 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; Respiratory support with HFNO (as opposed to NIV, as per standard of care)
Active Comparator: Non-Invasive Ventilation (NIV); 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; Respiratory support with Non-invasive ventilation, standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
feasilibity to perform a larger RCT inclusion rate	Inclusion rate	1 year
feasibility to perform a larger RCT screening rate	Screening rate	1 year
feasibility to perform a larger RCTperceived	perceived feasibility as qualified by staff and nurses	1 year
feasibility to perform a larger RCT protocol deviations	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
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
need for sedation	use of sedatives, and type of sedation	untill end of ICU admission
heart rate	beats per minute	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
respiratory rate	breaths per minute	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
blood pressure	systolic and diastolic pressure in mmHg	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
SpO2	peripheral saturation by pulsoxymeter (in %)	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
blood gas	with pH, PO2, PCO2, bicarbonate	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
dyspnea score	Borg dyspnea score (0-10 on VAS)	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
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 every 24 hours untill discharge
consciousness	glasgow coma scale (EMV)	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
agitation and sedation level	Richmond Agitation and Sedation scale (RASS)	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
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 every 24 hours untill discharge
HFNO ventilatory support parameters flow	flow in L/min	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
HFNO ventilatory support parameters FiO2	FiO2 in %	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
HFNO ventilatory support parameters temperature	temperature in Celcius	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
NIV ventilatory support parameters PEEP	PEEP in cmH2O	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
NIV ventilatory support parameters PS	PS in cmH2O	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
NIV ventilatory support parameters: FiO2	FiO2 in %	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
(dys)comfort score	10 point VAS scale	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
HACOR score	calculated from abovementioned parameters (pH, conciousness, PaO2/Fio2, respiratory rate)	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
facial pressure sores	scored daily: yes or no, and if yes: grade 1-4	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
nursing effort	respiratory support interventions per 2 hour by peat list	first 6 hours of study
nursing effort VAS	experienced nursing effort at a VAS scale from 1-10	at start, 1, 2, 6, 12, 24 and every 24 hours untill discharge
need for intubation and mechanical ventilation	intubation	during ICU admission
need for switch to other modality	cross over to NIV from HFNO or from HFNO to NIV	during ICU admission
reason of treatment failure	reason of treatment failure: clinical deterioration, failure to improve, other.	during ICU admission
expression of treatment failure	worsening of pH, PaCO2, respiratory rate, consiousness, agitation/discomfort, other	during ICU admission

Collaborators and Investigators

• Sponsor: Franciscus Gasthuis
• Collaborators: Reinier de Graaf Groep; Ikazia Hospital, Rotterdam; Haga Medisch Centrum
• Investigators: Principal Investigator: Dorien Kiers, MD, PhD, Franciscus Gasthuis & Vlietland

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2024
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 1, 2026

Study Registration Dates

• First Submitted: October 2, 2023
• First Submitted That Met QC Criteria: October 10, 2023
• First Posted (Actual): October 16, 2023

Study Record Updates

• Last Update Posted (Actual): August 21, 2025
• Last Update Submitted That Met QC Criteria: August 20, 2025
• Last Verified: August 1, 2025

More Information

Terms related to this study

• Other Study ID Numbers: HiCAP

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No