Closed-loop Oxygen Control for High Flow Nasal Therapy (HILOOP)

Safety and Efficacy of a Closed-loop Oxygen Control for High Flow Nasal Therapy in ICU Patients: a Randomized Cross-over Study (The HILOOP Study)

In patients with acute hypoxemic respiratory failure (AHRF), High Flow Nasal Therapy (HFNT) improves oxygenation, tolerance, and decrease work of breathing as compared to standard oxygen therapy by facemask. Current guidelines recommend adjusting oxygen flow rates to keep the oxygen saturation measured by pulse oximetry (SpO2) in the target range and avoid hypoxemia and hyperoxemia. The hypothesis of the study is that closed loop oxygen control increases the time spent within clinically targeted SpO2 ranges and decreases the time spent outside clinical target SpO2 ranges as compared to manual oxygen control in ICU patients treated with HFNT.

Study Overview

• Status: Completed
• Conditions: Respiratory Insufficiency; Hypoxemia; Acute Respiratory Failure; High Flow Nasal Cannula; Oxygen Therapy; Hyperoxemia
• Intervention / Treatment: Device: Oxygen close-loop; Device: No intervention

• Study Type: Interventional
• Enrollment (Actual): 53
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08035
    • Hospital Universitari Vall d'Hebron

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:

• Adult (>17yo) patients admitted to the ICU treated with HFNT for at least 8h
• Requiring FiO2 ≥ 30% to keep SpO2 in the target ranges defined by the clinician
• Written informed consent signed and dated by the patient or one relative in case that the patient is unable to consent, after full explanation of the study by the investigator and prior to study participation.

Exclusion Criteria:

• Patient with indication for immediate continuous positive airway pressure (CPAP), noninvasive ventilation (NIV), or invasive mechanical ventilation
• Hemodynamic instability defined as a need of continuous infusion of epinephrine or norepinephrine > 1 mg/h
• Low quality on the SpO2 measurement using finger and ear sensor (quality index below 60% on the Massimo SpO2 sensor, which is displayed by a red or orange colour bar)
• Severe acidosis (pH ≤ 7.30)
• Pregnant woman
• Patients deemed at high risk for need of mechanical ventilation within the next 8 hours
• Chronic or acute dyshemoglobinemia: methemoglobin, carbon monoxide (CO) poisoning, sickle cell disease
• Tracheotomised patient
• Formalized ethical decision to withhold or withdraw life support
• Patient under guardianship
• Patient deprived of liberties
• Patient included in another interventional research study under consent
• Patient already enrolled in the present study in a previous episode of acute respiratory failure

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Oxygen close-loop; Four hours period where the fraction of inspired oxygen delivered will be automatically titrated based on SpO2 values.	Device: Oxygen close-loop; The Automatic FiO2 option provides automated adjustment of the ventilator Oxygen setting to maintain the patient's SpO2 in a defined target range. When using the software option, the user defines the SpO2 target range, as well as the SpO2 emergency limits, and the device adjusts the Oxygen setting to keep the patient's SpO2 in the target range.
Active Comparator: Manual FiO2 adjustment; Four hours period where the fraction of inspired oxygen delivered will be manually adjusted by the healthcare personnel based on SpO2 values.	Device: No intervention; Manual FiO2 adjustment according to SpO2 values

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time spent in optimal SpO2 range	The optimal SpO2 range will be defined according to the SpO2 targets determined by the clinician.	4 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of time spent in sub-optimal SpO2 range	SpO2 values outside the optimal range but still within an acceptable limit (2-3 percent above and below the optimal range)	4 hours
Percentage of time spent out of range	Above or below the suboptimal limits specified at the begginning of the study	4 hours
Percentage of time with SpO2 signal available	Time with SpO2 signal available	4 hours
Mean SpO2/FiO2	Mean oxygenation value	4 hours
ROX index	Is a predictor of HFNT success/failure defined as (SpO2/FiO2)/respiratory rate	4 hours
Percentage of time with SpO2 below 88 and 85 percent	Duration of time with SpO2 <85 percent and <88 percent, respectively	4 hours
Number of events with SpO2 below 88 and 85 percent	Frequency of SpO2 decreases <85 percent and <88 percent, respectively	4 hours
Mean FiO2	Mean fraction of inspired oxygen	4 hours
Percentage of time with FiO2 below 40 percent and above 60%	Percentage of time that FiO2 is <40 percent and >60 percent, respectively	4 hours
Number of manual adjustments	Frequency of manual adjustments of FiO2	4 hours
Number of alarms	Frequency of alarms	4 hours
Patient comfort	Comfort score by visual analogic scale (from 0 to 10)	4 hours

Collaborators and Investigators

• Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Publications and helpful links

General Publications

• Helmerhorst HJ, Roos-Blom MJ, van Westerloo DJ, de Jonge E. Association Between Arterial Hyperoxia and Outcome in Subsets of Critical Illness: A Systematic Review, Meta-Analysis, and Meta-Regression of Cohort Studies. Crit Care Med. 2015 Jul;43(7):1508-19. doi: 10.1097/CCM.0000000000000998.
• L'Her E, Dias P, Gouillou M, Riou A, Souquiere L, Paleiron N, Archambault P, Bouchard PA, Lellouche F. Automatic versus manual oxygen administration in the emergency department. Eur Respir J. 2017 Jul 20;50(1):1602552. doi: 10.1183/13993003.02552-2016. Print 2017 Jul.
• Arnal JM, Garnero A, Novotni D, Corno G, Donati SY, Demory D, Quintana G, Ducros L, Laubscher T, Durand-Gasselin J. Closed loop ventilation mode in Intensive Care Unit: a randomized controlled clinical trial comparing the numbers of manual ventilator setting changes. Minerva Anestesiol. 2018 Jan;84(1):58-67. doi: 10.23736/S0375-9393.17.11963-2. Epub 2017 Jul 5.
• Roca O, Caritg O, Santafe M, Ramos FJ, Pacheco A, Garcia-de-Acilu M, Ferrer R, Schultz MJ, Ricard JD. Closed-loop oxygen control improves oxygen therapy in acute hypoxemic respiratory failure patients under high flow nasal oxygen: a randomized cross-over study (the HILOOP study). Crit Care. 2022 Apr 14;26(1):108. doi: 10.1186/s13054-022-03970-w.

Study record dates

Study Major Dates

• Study Start (Actual): April 27, 2021
• Primary Completion (Actual): August 10, 2021
• Study Completion (Actual): August 10, 2021

Study Registration Dates

• First Submitted: May 4, 2021
• First Submitted That Met QC Criteria: July 7, 2021
• First Posted (Actual): July 16, 2021

Study Record Updates

• Last Update Posted (Actual): December 9, 2021
• Last Update Submitted That Met QC Criteria: November 26, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: High flow nasal cannula; Hypoxemia; Nasal high flow; Hyperoxemia; Oxygen close-loop
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Respiratory Insufficiency; Hypoxia
• Other Study ID Numbers: PR(AG)539/2020

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