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High-flow Air Via Nasal Cannula vs Non-invasive Continuous Positive Airway Pressure for Hypercapnic Respiratory Failure (HIGHforHyper)

Primary Purpose

Hypercapnic Respiratory Failure

Status
Unknown status
Phase
Not Applicable
Locations
Austria
Study Type
Interventional
Intervention
High flow nasal cannula
Continuous positive airway pressure
Sponsored by
Medical University of Vienna
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypercapnic Respiratory Failure

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Adult patients (e.g. at least 18 years old) treated at the Emergency Department
  • Acute hypercapnic respiratory failure defined as a pCO2 >50mmHg and a pH<7.30 on admission

Exclusion Criteria:

  • Patients being comatose on admission, with no intact airway, lack of airway-protective reflexes, or those who are not alert enough to follow commands
  • Patients intubated by Emergency Medical Service
  • Patients requiring intubation on admission
  • Pregnant women

Sites / Locations

  • Medical University ViennaRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Active Comparator

Arm Label

Intervention

Control

Arm Description

Intervention consists of HFA using standard equipment at the department. A gas flow of 60L/min and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the pati ent or indication for intubation.

Control consists of non-invasive CPAP ventilation support using a tight mask and standard respirator equipment of the Department of Emergency Medicine. A positive airway pressure of 5cm H2O and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation.

Outcomes

Primary Outcome Measures

Change of pCO2 in arterial blood gas
The investigators assume baseline pCO2-levels of 50 to 100 mmHg in arterial blood gas, measured every 60 minutes.

Secondary Outcome Measures

Frequency of therapy failure
switch to other therapy; intubation
Patient's perception of the therapy
from very comfortable to very uncomfortable, using visual analogue scale
Rate of adverse events
e.g. apnoea, cardiac arrythmics
Time until pCO2 reaches 50mmHg or less
Time until pCO2 reaches 50mmHg or less
Length of Stay at the Emergency Department
Hours until the patient is transferred to the ward/ICU or discharged
Admissions to ICU
Frequency of admission to ICU
Admissions to regular ward
Frequency of admission to regular ward
Length of Stay at the ICU
Hours until the patient is transferred to the regular ward
Length of Stay at the Hospital
Hours until the patient is discharged
Hospital readmissions
Frequency of hospital readmissions

Full Information

First Posted
May 6, 2019
Last Updated
February 18, 2020
Sponsor
Medical University of Vienna
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1. Study Identification

Unique Protocol Identification Number
NCT03944525
Brief Title
High-flow Air Via Nasal Cannula vs Non-invasive Continuous Positive Airway Pressure for Hypercapnic Respiratory Failure
Acronym
HIGHforHyper
Official Title
High-flow Air Via Nasal Cannula Versus Non-invasive Continuous Positive Airway Pressure Ventilation Support for Hypercapnic Respiratory Failure The HIGH-for-HYPER Study
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 1, 2020 (Actual)
Primary Completion Date
December 31, 2020 (Anticipated)
Study Completion Date
June 30, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Medical University of Vienna

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
The study will be performed as a randomized controlled non-inferiority trial. HFA has been increasingly used in the last years to treat hypoxic respiratory failure (i.e. type I failure), and numerous studies have shown its efficiency in this indication. Despite this good evidence for HFA in hypoxic respiratory failure, it has only reluctantly been used for hypercapnic respiratory failure. HFA has been shown to generate PEEP, despite not being a closed system, and to improve CO2 clearance by flushing anatomical dead space. It might also help to reduce inspiratory resistance and facilitate secretion clearance from humidified gas. A study on COPD patients showed an increase in breathing pressure amplitude and mean pressure, as well as tidal volume, with a trend towards reduction of carbon dioxide partial pressure. Intervention consists of HFA using standard equipment at the department. A gas flow of 60 litres per minute and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50 mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation. Control consists of non-invasive continuous positive airway pressure ventilation support using a tight mask and standard respirator equipment of the Department of Emergency Medicine. A positive airway pressure of 3,67 mmHg and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50 mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation.
Detailed Description
Respiratory failure is a leading cause of morbidity and mortality, and one of the most frequently encountered problems at the emergency department. Hypercapnic or hypercarbic respiratory failure, also dubbed respiratory failure type II, is characterized by failure of the respiratory system in one of its two gas exchange functions: carbon dioxide (CO2) elimination. It is thus usually defined via partial pressure of CO2 in the arterial blood gas (PaCO2), a value greater than 50 mmHg being a commonly used cut-off. Hypercapnic respiratory failure is often associated with severe airway disorders, such as asthma and chronic obstructive pulmonary disease (COPD), but might also be found in other conditions, where respiratory drive is restricted, such as intoxications, neuromuscular diseases or chest wall abnormities. Hypercapnic respiratory failure, i.e. respiratory failure type II, is often associated with hypoxemic respiratory failure, i.e. respiratory failure type I, failure of oxygenation. However, type I failure is also often observed without hypercapnia. Respiratory failure, both type I and II, may be further classified into either acute or chronic. Distinction between both forms is often challenging, and, in addition to arterial blood gas analysis, might require additional tests to identify clinical markers such as polycythemia or pulmonary heart disease. For practical reasons, acute respiratory failure is often defined as a condition, in which respiratory failure develops too fast to allow for renal compensation and an increase in bicarbonate (HCO3-) levels, and thus leading to acidosis (pH less than 7.3). Therapeutic strategies for hypercapnic respiratory failure include non-invasive CPAP ventilation support, intubation and mechanical ventilation (both assisted and controlled forms), and, in very severe cases, extracorporeal methods, such as extracorporeal life support systems. Non-invasive CPAP ventilation support via either helmets, or different kinds of tight masks, is the current method of choice for the treatment of patients with acute respiratory failure in the intensive care setting. Eligible patients include those with an intact airway, airway-protective reflexes, who are alert enough to follow commands, whereas patients who lack those criteria require immediate endotracheal intubation. Non-invasive CPAP ventilation support improves both oxygenation (by providing an inspired fraction of oxygen (FiO2) of 100%, which is not possible via a simple venturi-mask, and the possibility of positive end-expiratory pressure (PEEP), preventing collapsing of the alveoli), and decarboxylation (by increasing tidal volume). It has been shown to decrease both need for intubation and in-hospital mortality. Non-invasive CPAP ventilation support, however, requires a high grade of skill from providers, and intensive communication with the patient to explain the usefulness of a tight-sitting device in the face in a situation of perceived massive dyspnea. Although severe adverse effects of non-invasive CPAP ventilation support are very rare, pain and pressure marks may occur. Despite all efforts of care providers, there is a relevant proportion of patients who do not tolerate ventilation support via a tight mask at all. About 15% of patients not tolerating the therapy, with an additional 25% of patients presenting with contraindications. These might include general contraindications against non-invasive techniques, such as aforementioned lack of airway-protective reflexes, but also such specific for tight masks, such as anatomical abnormities of the face. High-flow Air via Nasal Cannula (HFA) therapy is usually applied via a wide-bore nasal cannula. It provides up to 60 litres per minute of a heated and humidified gas mixture (with an adjustable FiO2). This therapy is much less invasive for the patient, and thus often better tolerated. HFA has been increasingly used in the last years to treat hypoxic respiratory failure (i.e. type I failure), and numerous studies have shown its efficiency in this indication both at the intensive care unit and at the emergency. A recent systematic review and meta-analysis has concluded in improved patient comfort and reduced dyspnea scores. Despite this good evidence for HFA in hypoxic respiratory failure, it has only reluctantly been used for hypercapnic respiratory failure. This might be explained in a large part by the fact that patients with chronic hypercapnia are known to diminish their respiratory drive when exposed to hyperoxia. However, evidence has begun to change on this indication in recent time. HFA has been shown to generate PEEP, despite not being a closed system, and to improve CO2 clearance by flushing anatomical dead space. It might also help to reduce inspiratory resistance and facilitate secretion clearance from humidified gas. A study on COPD patients showed an increase in breathing pressure amplitude and mean pressure, as well as tidal volume, with a trend towards reduction of pCO2. Based on these findings, the use of HFA has increased in clinical practice, and a number of case reports and -series indicate successful use. Fraser et al. successfully investigated the use of HFA in patients with chronic COPD changes in arterial blood gases during use of HFA in the ED for both hypercapnic and non-hypercapnic patients were analyzed in previous studies, and found a significant reduction of pCO2. There is, however, to date no randomized controlled trial investigating the effect of HFA in acute hypercapnic respiratory failure. The study will be performed as a randomized controlled non-inferiority trial. The study site is the Department of Emergency Medicine (ED) at the Vienna General Hospital, a leading academic research center for emergency medicine at a large, tertiary care hospital. Around 90,000 patients are being treated at the department each year, approximately 150-200 of them suffering from hypercapnic respiratory failure, and requiring non-invasive ventilation support. The department features its own ICU and intermediate-care unit, with 7 positions each, for a total of 14 positions capable of providing CPAP therapy. The HFA-device is also at regular use at the department. Patients who are temporary not able to give informed consent due to hypercapnia will be randomized and treated. They will be informed post-hoc as soon as they are able to give informed consent, and will have the possibility to give consent to the use of their data. A random sequence will be generated by a person not involved in the enrolment of patients using standard software. Randomisation will be performed in variable blocks of 4 to 6, to yield an unpredictable allocation yet warranting balanced group sizes. Sequentially numbered sealed opaque envelopes (SNOSE), containing allocation either to the intervention or the control group, will be pre-produced. The envelopes will be opened after consent immediately before the start of the intervention to allow for allocation concealment and reduce the risk of immediate post-random exclusion. Intervention consists of HFA using standard equipment at the department. A gas flow of 60 litres per minute and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50 mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation. Control consists of non-invasive CPAP ventilation support using a tight mask and standard respirator equipment of the Department of Emergency Medicine. A positive airway pressure of 3,67 mmHg and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50 mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation. Based on treating physician's discretion, both intervention and control treatments might be aborted at any time, and any other therapy (simple Venturi-Mask, HFA, non-invasive CPAP-ventilation support, intubation, extracorporeal methods) might be initiated. Baseline characteristics and demographic variables will include age, sex, smoking status, prior diseases, especially any history of COPD or asthma, and duration of treatment of those, medication, body size, pre-hospital treatment. pCO2 levels will be measured using blood gas analysis at 0 -30 -60 (and every 60 minutes thereafter) minutes after the beginning of the therapy, and at the end of the therapy. Patient's perception of the therapy will be assessed after the end of the therapy using a 10-point Likert-Scale from very uncomfortable to very comfortable. Sample size considerations are based on the primary outcome pCO2 reduction per hour. The investigators assume baseline pCO2-levels of 50 to 100 mmHg. Based on the published literature, the investigators assume that the outcome in the control group is 4±3mmHg/hour. Based on our clinical judgment the investigators assumed a limit of non-inferiority of 2 mmHg, which lies well within one standard deviation of the outcome. Hence, the investigators would need 28 experimental subjects and 28 control subjects to be able to reject the null hypothesis that the lower limit of a two-sided 90% confidence interval of the true difference between two groups is above the non-inferiority limit, at a power of 80%. Formally the investigators will have to enroll 56 patients. To allow for potential loss to follow up, missing data, measurement issues, or other design factors the investigators will increase actual sample size to 62. In terms of feasibility, the investigators expect approximately 150 to 200 eligible patients within one year, resulting in an expected study-duration of approximately 6 months. Due to the relatively small sample size, there are no preplanned interim analyses. Baseline data and demographics will be tabulated for the intervention- and control-group to assess success of randomisation. Reduction of pCO2 per hour will be compared between individuals in the intervention and individuals in the control group. The investigators will calculate effects as differences with 95% confidence intervals. This will be done using a linear mixed model with pCO2 as the outcome, treatment group as a factor variable, and baseline pCO2 and treatment time as covariates. The investigators will assume non-inferiority if the two-sided 95% confidence interval lies within predefined limits of non-inferiority. As a sensitivity analysis the investigators will also test for time/treatment-interaction in the model. As another sensitivity analysis, the investigators will analyze data during first 6 hours of treatment at maximum. In case of therapy failure, the investigators will use the last-observation-carried-forward method to 6 hours. Primary analysis will follow the intention-to-treat principle. The unit of analysis will be single persons. Categorical secondary outcomes will be analysed by calculating relative risks with exact standard error based 95% confidence intervals. The investigators will assume non-inferiority if the two-sided 95% confidence interval lies within predefined limits of non-inferiority. Continuous secondary outcomes will be analyzed like the primary outcome. Length of stay data are expectedly lognormally distributed, therefore the investigators plan to use log-transformed values for further calculations. For data analysis the investigators will use Stata 11. A two-sided p-value less 0.05 is generally considered statistically significant. Reporting will follow the standards of the CONSORT extension for non-inferiority and equivalence trials. Privacy and Data safety Directly and indirectly patient-related data will be stored physically and logically separated. In addition, only members of the study-group will have access to study data. Data will be stored on a secured computer of the department of emergency medicine and will be accessible only via restricted access for members of the study-group.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypercapnic Respiratory Failure

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Model Description
The study will be performed as a randomized controlled non-inferiority trial. The study site is the Department of Emergency Medicine (ED) at the Vienna General Hospital, a leading academic research center for emergency medicine at a large, tertiary care hospital. Around 90,000 patients are being treated at the department each year, approximately 150-200 of them suffering from hypercapnic respiratory failure, and requiring non-invasive ventilation support. The department features its own ICU and intermediate-care unit, with 7 positions each, for a total of 14 positions capable of providing CPAP therapy. The HFA-device is also at regular use at the department.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
62 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Intervention
Arm Type
Active Comparator
Arm Description
Intervention consists of HFA using standard equipment at the department. A gas flow of 60L/min and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the pati ent or indication for intubation.
Arm Title
Control
Arm Type
Active Comparator
Arm Description
Control consists of non-invasive CPAP ventilation support using a tight mask and standard respirator equipment of the Department of Emergency Medicine. A positive airway pressure of 5cm H2O and a FiO2 as clinically feasible will be used. Therapy will be continued until a pCO2-level of 50mmHg or less is reached, or therapy has to be aborted because of lack of tolerance by the patient or indication for intubation.
Intervention Type
Device
Intervention Name(s)
High flow nasal cannula
Intervention Description
Oxygen-therapy via HFNC
Intervention Type
Device
Intervention Name(s)
Continuous positive airway pressure
Intervention Description
Non-invasive CPAP ventilation
Primary Outcome Measure Information:
Title
Change of pCO2 in arterial blood gas
Description
The investigators assume baseline pCO2-levels of 50 to 100 mmHg in arterial blood gas, measured every 60 minutes.
Time Frame
first 24 hours
Secondary Outcome Measure Information:
Title
Frequency of therapy failure
Description
switch to other therapy; intubation
Time Frame
first 24 hours
Title
Patient's perception of the therapy
Description
from very comfortable to very uncomfortable, using visual analogue scale
Time Frame
first 24 hours
Title
Rate of adverse events
Description
e.g. apnoea, cardiac arrythmics
Time Frame
first 24 hours
Title
Time until pCO2 reaches 50mmHg or less
Description
Time until pCO2 reaches 50mmHg or less
Time Frame
first 24 hours
Title
Length of Stay at the Emergency Department
Description
Hours until the patient is transferred to the ward/ICU or discharged
Time Frame
first 24 hours
Title
Admissions to ICU
Description
Frequency of admission to ICU
Time Frame
first 24 hours
Title
Admissions to regular ward
Description
Frequency of admission to regular ward
Time Frame
first 24 hours
Title
Length of Stay at the ICU
Description
Hours until the patient is transferred to the regular ward
Time Frame
first 24 hours
Title
Length of Stay at the Hospital
Description
Hours until the patient is discharged
Time Frame
first 24 hours
Title
Hospital readmissions
Description
Frequency of hospital readmissions
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Adult patients (e.g. at least 18 years old) treated at the Emergency Department Acute hypercapnic respiratory failure defined as a pCO2 >50mmHg and a pH<7.30 on admission Exclusion Criteria: Patients being comatose on admission, with no intact airway, lack of airway-protective reflexes, or those who are not alert enough to follow commands Patients intubated by Emergency Medical Service Patients requiring intubation on admission Pregnant women
Facility Information:
Facility Name
Medical University Vienna
City
Vienna
ZIP/Postal Code
1180
Country
Austria
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Verena Fuhrmann, Dr.med.univ.
Phone
004314040019640
Email
verena.fuhrmann@meduniwien.ac.at

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

High-flow Air Via Nasal Cannula vs Non-invasive Continuous Positive Airway Pressure for Hypercapnic Respiratory Failure

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