Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT06110390 |
| Other study ID # |
MRC-01-18-470 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
October 17, 2020 |
| Est. completion date |
February 2024 |
Study information
| Verified date |
October 2023 |
| Source |
Hamad Medical Corporation |
| Contact |
Gustav F Strandvik, MBChB |
| Phone |
+97440253769 |
| Email |
gstrandvik[@]hamad.qa |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
A significant proportion of patients who are intubated for trauma-related injuries, will fail
the extubation process. This means that, when the decision has been made to remove the
endotracheal tube, a certain proportion of these patients will require the endotracheal tube
to be re-inserted. Global estimates for the rates of re-intubation range from 5-15% of all
patients who have had attempted extubation on Intensive Care Units. The exact figures for
intubated victims of trauma are not available. Re-intubation is associated with increased
intensive care and hospital length of stay, increased morbidity, and the physical risks to
the patient inherent with the intubation process. There is also some evidence that the rates
of tracheostomy are higher in patients who have failed extubation. A number of interventions
have been developed to help prevent extubation failure. Non-invasive ventilation and
high-flow nasal oxygen are routinely employed in practice. However, there have been no
specific studies of these interventions in TICU patients. High-flow nasal oxygen therapy
(HFNO) has emerged over the last decade as a viable adjunct in the management of patients
suffering from, or at risk of, hypoxemic respiratory failure. Within the intensive care unit
settings, HFNO has been studies in terms of preventing intubation, but it has been evaluated
more often in terms of preventing extubation failure.
Our study aims to answer the question of whether HFNO is effective at preventing extubation
failure in intubated and ventilated victims of traumatic injuries. Previous studies on the
same subject, are not based on unequivocal, robust RCTs with low risk of bias. Our primary
outcome measure is re-intubation rates and secondary outcome measures are CO2 accumulation
rates, atelectasis rates, nutrition status within first 24 hours post extubation, and post -
extubation rates of vomiting. Ours will be a prospective, randomized clinical control study.
There will be three arms to the study: a control arm, and two intervention arms.
Randomization will be done on a permuted block basis. The control arm will be patients
receiving standard oxygen therapy, and the intervention arms will be either High Flow Nasal
Oxygen Therapy or Non-invasive Ventilation via mask. We propose that, when compared with
either face-mask O2, NIV (CPAP), HFNO administered continuously for 24 hours post extubation
of trauma patients on ICU, will result in better patient-related outcomes.
Description:
High-flow nasal oxygen therapy (HFNO) has emerged over the last decade as a viable adjunct in
the management of patients suffering from, or at risk of, hypoxemic respiratory failure. The
mechanisms of its therapeutic benefit are not precisely understood but are thought to include
a small but significant continuous positive airway pressure effect, and in the context of
critically ill patients, the use of HFNO has been studied for the prevention of intubation,
or as an alternative to Noninvasive Ventilation (NIV) for the prevention of intubation, in
Type I respiratory failure patients, mostly with COPD or Heart Failure. Within the intensive
care unit itself, HFNO has been studies in terms of preventing intubation, but it has been
evaluated more in terms of preventing extubation failure. However, there have been no
specific studies in Trauma Intensive Care Unit (TICU) patients. Patients suffering with
polytrauma, who survive to TICU admission, are a unique population. There is a significant
incidence of confusion and/or delirium post-extubation. In patients with respiratory failure
post extubation, it is postulated (1) that the impaired mental state, however mild, may cause
patients to a) be unable to tolerate NIV, b) swallow more air (on NIV) due to mild bulbar
dysfunction, thus leading to an increased risk of regurgitation and possible aspiration
pneumonitis. Furthermore, the use of NIV may c) impair effective oral nutrition in those
patients without an NJ tube placed.
Re-intubation (failed extubation) is defined variably as the need to intubate a patient
within 72 hours of extubation in the critical care unit. Re-intubation is associated with
increased intensive care and hospital length of stay, increased morbidity, and the physical
risks to the patient inherent with the intubation process. It is unclear which, if any,
interventions can help reduce the rate of extubation failure in Trauma Intensive Care
patients.
In this research study we are focusing on HFNO compared with NIV and conventional oxygen
therapy in trauma patients to avoid reintubation.
We propose that, when compared with either face-mask oxygen, NIV (CPAP), HFNO administered
continuously for 24 hours post extubation of trauma patients on ICU, will result in better
patient-related outcomes.
Primary outcome measure:
Our primary outcome measure is re-intubation rate within 72 hours of extubation
Secondary outcome measures:
Our secondary outcomes measures are CO2 accumulation rates, atelectasis rates, nutrition
status within first 24 hours post extubation, and post-extubation rates of vomiting.
Study design:
Prospective, randomized clinical control study. There will be three arms to the study: a
control arm, and two intervention arms. Randomization will do on a permuted block basis. The
control arm will be patients receiving standard oxygen therapy, and the intervention arms
will be either High Flow Nasal Oxygen Therapy, or Non-invasive Ventilation via mask.
Study population:
All patients intubated on the Trauma Intensive Care Unit at Hamad General Hospital will be
considered eligible for the study. Written informed consent will be obtained from next of kin
(NOK) if available or by the treating physician as a surrogate if the NOK are not available.
Study Population
Inclusion criteria: Adult intubated and ventilated patients who are victims of trauma and are
being cared for on the Trauma Intensive Care Unit will be considered eligible for the study
when they are considered fit for extubation.
Exclusion criteria:
- Patients who cannot be extubated (including patients requiring tracheostomy)
- Patients with cribriform plate fractures
- Patients with nasal occlusion for any reason
- Patients with unstable mid-face fractures
Sample size estimation:
Based on an anticipated improvement rate of 25% reduction in extubation failure (from 8% to
6%), using High-flow nasal Oxygen Therapy and NIV (CPAP) with margin of error of 5%, and
confidence level of 95%, a total of 100 intubated trauma patients needs to be included in the
study (50 for each group). Moreover, 50 patients with facemask O2 will be included as a
comparative or control group.
The equation used for estimation of sample size:
The standard normal deviate for α = Zα = 1.960 The standard normal deviate for β = Zβ = 1.645
Pooled proportion = P = (q1*P1) + (q0*P0) = 0.103 A = Zα√P(1-P) (1/q1 + 1/q0) = 2.198 B =
Zβ√P1(1-P1) (1/q1) + P0(1-P0) (1/q0) = 2.878 C = (P1-P0)2 = 0.292 Total group size = N =
(A+B)2/C = 88 Continuity correction (added to N for Group 0) = CC = 1/ (q1 * |P1-P0|) = 23
So, a total of 113 cases are required for this study (38 cases in each group), since the
target reduction of extubation failure (effect size is small from 8% to 6% i.e., 25%) we
prefer to include 50 cases in each group.
Allocation ratio: 1:1:1
Study procedures:
1. The enrollment for the study will begin once patient is ready for extubation and at the
same time will be randomized to the study arms.
2. All intubated patients with next of kin /deferred consent will be enrolled
3. The respiratory therapist will apply the intervention type based on physician order
The study participants will be unblinded, as intervention is in the form of face mask O2,
High flow nasal oxygen and NIV. These cannot be used in a blind approach.
We have developed a flow-chart for the study participants, which include an escalation
pathway. If HFNO fails, patients are escalated to NIV- CPAP. If Facemask O2 fails, patients
are escalated to HFNO or NIV, depending on treating clinician preference. The maximum
observation time allowed to test whether intervention is effective is one hour. Re-intubation
requirement will be assessed by treating clinician depending on ABG/oxygenation/CO2 or WOB
criteria, or 'clinician-judgement'. This may occur at any time.
Screening and enrollment: The data will be prospectively collected for all intubated enrolled
patients admitted to the Hamad General Hospital trauma ICU between 1 October 2020 and 31
December 2023.
all ventilated patients will be recruited based on next of kin/deferred consent during the
study period for the study in trauma ICU. The enrollment of the patients will be for 3 years
from start of study period
Follow up: Each patient will be followed up for 72 hours post extubation as a part of study
Informed Consent:
Unconscious patients with severe injury will not be able to provide informed consent. This
trial will therefore use "Exception from Informed Consent Requirements for Emergency
Research" (Policy # RES 11026) which involves the most vulnerable population of study
subjects (i.e., a population with no capacity to control what happens to them and no capacity
to consent, where the emergency circumstances require prompt action and generally provide
insufficient time and opportunity to locate and obtain consent from each subject's family
member).
Every possible effort will made to contact the subject's family member to obtain consent.
However, it may be difficult to contact family members of migrant workers within the initial
time frame in the emergency department. In such situation, initially the deferred consent
document will be signed by two privileged physicians, one of whom will be the treating
physician. After regaining complete consciousness patient will be asked for continuation in
the study and if the subject agrees written informed consent will be obtained.
As soon as is reasonably possible and appropriate the patient's NOK/person responsible will
be informed of the patient's inclusion in the research and will be informed of the option to
withdraw the patient from it without any reduction in quality of care. If the NOK/person
responsibly chooses to withdraw their consent for continued participation, they will be asked
for permission to use the data collected up to that time.
Patients who recover sufficient cognition to understand the explanation of the study will be
asked to consent to continue in the study or be offered the chance to withdraw. If the
patient chooses to withdraw from the study, they will be asked for permission to use their
data up to the time of withdrawal.
All interaction between research staff and participants and their relatives will take into
consideration the stress or emotional factors associated with critical illness and ensure
that the dependency of potential participants and their relatives on medical personnel
providing treatment does not compromise their actual or perceived freedom of decision making
to participate.
Risk This study does not add any novel risks to patients as all the interventions are
currently used as part of standard bundles of care. Potential complications include local
trauma, discomfort and pressure areas, epistaxis and gastric distension from the use of NIV.
Dry airways are a potential complication of both face mask O2 and HFNCO2. These risks are the
same as if the patients are receiving a standard clinical care of treatment or not
participating in the research
Data Collection & Integrity:
The data will be prospectively collected for all intubated enrolled patients admitted to the
Hamad General Hospital trauma ICU from 1 October 2020 to 31 December 2023. Patient data
includes Age, Gender, Mechanism of injury, associated injury, Date & time of Trauma, arrival
to Trauma room, admission, Vital signs in Trauma ICU, GCS, intubation date, and injuries,
duration of hospital, ICU stay and mortality.
Most importantly, the group allocation will be to Facemask O2, NIV-CPAP, or HFNO. We will
compare the rates of re-intubation using a p-value of < 0.05 to confirm a statistical
difference.
Data will be anonymously collected, and the data sheet will be secured with the principal
investigator. The name of the patients will not be disclosed and kept confidential. The study
is complying with the "Records-based study" profile that was described by corresponding
section of the collaborative Intuitional Training Initiative (CITI). Patients' name and HC
numbers will be used temporarily and only upon data collection and cleaning, to prevent
duplication and allows proper re-access to the corresponding data to refine them. Both the
name and HC number will be deleted immediately after data entry and coding.
Data will be presented as proportions, medians, or mean ± standard deviation (SD) as
appropriate. Differences in categorical variables between respective groups will be analyzed
using the chi square test. The continuous variables will be analyzed using Student's t-test.
For skewed continuous data non-parametric Mann-Whitney test will be performed. Two-tailed P
values of <0.05 will be considered significant. Data analysis will be carried out using the
Statistical Package for Social Sciences version 18 (SPSS Inc. USA).
Quality Assurance, Monitoring & Safety:
The research team will be responsible for the data collection, entry, confidentiality and
maintaining the quality of the data. It will also oversee the ethical conduct of the trial,
safety, protection, privacy and confidentiality of the subjects and adherence to the study
protocol. We will follow the instructions from institutional review committee to setup any
independent monitoring committee, if needed.
