High VS Low Flow Nasal O2 for Acute Hypercapnic Respiratory Failure

High Flow Nasal Cannula Therapy for Initial Oxygen Administration in Acute Hypercapnic Respiratory Failure - A Comparison Study of Two Current Standards of Care

Chronic lung conditions such as smoking related lung damage lead to breathing fail. This results in accumulation of gases such as carbon-di-oxide in the body especially during periods of illness known as exacerbation.

Current management of carbon-di-oxide accumulation is administration of oxygen, nebulisers, antibiotics etc and if necessary, provide a tight fitting mask around the face to provide breathing support. If this fails, then a patient is placed on a mechanical ventilator. The tight fitting mask therapy is also called non-invasive ventilation and is used widely but patients acceptability of the therapy is limited.

Providing a high flow of air with some oxygen could potentially provide the same benefit of the non-invasive ventilation and may also be better accepted by patients.

Currently the knowledge and evidence from studies suggest a beneficial role for this high flow therapy but this has not been investigated in well designed studies.

In the proposed study we aim to investigate whether use of the high flow therapy reduces the need for non-invasive ventilation in patients who present with a recent onset accumulation of carbon-di-oxide in their body due to long-term lung disease. If this shows benefit, it will lead to a bigger trial with patient benefiting by reduction in the non-invasive ventilation or indeed a need for an invasive breathing machine.

Study Overview

• Status: Recruiting
• Conditions: Acute Hypercapnic Respiratory Failure; Acute Exacerbation of COPD
• Intervention / Treatment: Device: High flow nasal therapy; Device: Low flow oxygen

• Study Type: Interventional
• Enrollment (Anticipated): 82
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Murali Shyamsundar, MD, PhD; Phone Number: +44 (0)28 9097 6381; Email: Murali.Shyamsundar@qub.ac.uk
• Study Contact Backup: Name: Asem Alnajada, MSc; Email: aalnajada01@qub.ac.uk

Study Locations

• United Kingdom
  • Belfast, United Kingdom
    • Recruiting
    • Royal Victoria Hospital
  • Belfast, United Kingdom
    • Recruiting
    • Mater Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Adult patients > 18 years of age
2. Acute Hypercapnic respiratory failure with pH < 7.35 and pCO2 > 6 KPa

Exclusion Criteria:

1. Age < 18 years
2. Pregnant or Breast-Feeding
3. Patient cannot read and understand English
4. Hypercapnia secondary to a drug toxicity or non-pulmonary aetiology
5. Hypercapnia secondary to exacerbation of asthma
6. Contraindication to NIV
7. Contraindication to HFNC
8. Not for escalation to NIV
9. pH < 7.15
10. GCS 8 or less
11. Shock defined as systolic < 90 mmHg or a reduction by 20mmHg from usual systolic BP despite volume resuscitation
12. Respiratory or cardio-respiratory arrest
13. Any other indication that requires immediate invasive/non-invasive mechanical ventilation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: High flow nasal therapy (HFNT); Characterized by an elevated arterial CO2 (PaCO2) level of > 6kPa due to ventilatory failure. The ventilatory failure relates to the imbalance between the respiratory demand and the capacity of the respiratory system to match the demand.	Device: High flow nasal therapy; Controlled oxygen administration using at least 20 L/min of flow rate and titrated up as tolerated. Titration of supplemental oxygen to an arterial saturation between 88 - 92%.; Other Names: High flow nasal insufflation
ACTIVE_COMPARATOR: Low flow oxygen (LFO); Characterized by an elevated arterial CO2 (PaCO2) level of > 6kPa due to ventilatory failure. The ventilatory failure relates to the imbalance between the respiratory demand and the capacity of the respiratory system to match the demand.	Device: Low flow oxygen; Controlled oxygen administration using (venturi mask or nasal cannulae) titrated to an arterial saturation between 88 - 92% as the initial oxygen administration method with a flow rate of <20 L/min.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients requiring NIV in each cohort	Proportion of patients who require NIV by 6 hours of intervention.	6 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PaCO2 in Kilopascal	Blood arterial PCO2 level measured at the pre-specified timepoints or at the nearest timepoint.	1 hour, 6 hours and 24 hours.
PaO2 in Kilopascal	Blood arterial PaO2 level measured at the pre-specified time-points or at the nearest time-point.	1 hour, 6 hours and 24 hours.
pH	pH measured for acid-base status.	1 hour, 6 hours and 24 hours.
Respiratory rate (Breath/minute)	Rate of breathing per minute as documented in medical notes.	At 1 hour, 6 hours and 24 hours.
Heart rate (Beat/minute)	Heart rate per minute as documented in medical notes.	1 hour, 6 hours and 24 hours.
Mean arterial pressure in millimeters of mercury	Mean arterial pressure in millimeters of mercury as documented in medical notes	1 hour, 6 hours and 24 hours.
Intubation rate		1 hour, 6 hours and 24 hours.
ICU admission		From the date of randomization until the date of first documented admission to ICU, assessed up to 12 weeks.
In-hospital mortality		From the date of randomization until the date of death or hospital discharge, whichever came first, assessed up to 12 weeks.
ICU length of stay		From the date of ICU admission until the date of last documented ICU discharge or date of death from any cause, whichever came first, assessed up to 12 weeks.
Hospital length of stay		From the date of randomization until hospital discharge or date of death from any cause, whichever came first, assessed up to 12 weeks.
Dyspnoea	Dyspnoea will be assessed assessment using a visual analogue scale (VAS), score range 0-10, higher values represent a better outcome)) if patient has capacity or the Likert scale (score range 1-5; higher values represent a better outcome) to be completed by the clinical team (doctor/nurse/physio) if the patient lacks capacity.	1 hour, 6 hours and 24 hours.
Patient comfort	Comfort will be assessed assessment using a visual analogue scale (VAS), score range 0-10, higher values represent a better outcome)) if patient has capacity or the Likert scale (score range 1-5; higher values represent a better outcome) to be completed by the clinical team (doctor/nurse/physio) if the patient lacks capacity.	1 hour.

Collaborators and Investigators

• Sponsor: Belfast Health and Social Care Trust

Publications and helpful links

General Publications

• Alnajada A, Blackwood B, Mobrad A, Akhtar A, Shyamsundar M. High-flow nasal cannula therapy for initial oxygen administration in acute hypercapnic respiratory failure: study protocol of randomised controlled unblinded trial. BMJ Open Respir Res. 2021 Jan;8(1):e000853. doi: 10.1136/bmjresp-2020-000853.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 13, 2021
• Primary Completion (ANTICIPATED): March 1, 2023
• Study Completion (ANTICIPATED): March 1, 2023

Study Registration Dates

• First Submitted: September 11, 2020
• First Submitted That Met QC Criteria: November 20, 2020
• First Posted (ACTUAL): November 23, 2020

Study Record Updates

• Last Update Posted (ACTUAL): April 21, 2022
• Last Update Submitted That Met QC Criteria: April 14, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: High flow nasal oxygen; Acute exacerbation of COPD; High flow nasal insufflation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypercapnia
• Other Study ID Numbers: 19106MA-AS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: IPD may be shared on request to the Principal Investigator and will be decided on a case by case basis.

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