Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT04269161 |
| Other study ID # |
2003117 |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
N/A
|
| First received |
|
| Last updated |
|
| Start date |
May 24, 2022 |
| Est. completion date |
May 17, 2024 |
Study information
| Verified date |
May 2023 |
| Source |
University of Missouri-Columbia |
| Contact |
John A Pardalos, MD |
| Phone |
(573) 882-2272 |
| Email |
Pardalosj[@]health.missouri.edu |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Prematurely born infants in the hospital neonatal intensive care unit (NICU) will be included
in the study. This clinical trial is a randomized crossover study to show that our automated
oxygen control device performance is no worse than a NICU nurse in keeping a premature
neonate's SPO2 within the prescribed range. Since subjects receive the device (automatic
oxygen control) and the standard of care (manual control by a nurse), every subject serves as
their own perfectly matched control. Performance measures include the average time it takes
for the SpO2 to return to the desired range (primary endpoint) and the total amount of time
that the SpO2 is within the desired range (secondary endpoint). The device will be applied to
premature infants on respiratory support humidified high flow nasal cannula (HFNC) with
oxygen controlled using a blend valve. Two groups include one that begins the study period
with the device and one that begins the study period without the device. The two groups are
switched between manual and automatic every 6 hours into the trial period and complete a
total of 6 days. The target number of subjects is 60. We will analyze the study as a
superiority trial if there is strong evidence of superiority.
Description:
We intend to enroll between 20-30 subjects at each of two separate institutions (University
of Missouri Women's and Children's Hospital and Studer Family Children's Hospital in
Pensacola, FL). The subjects will be premature infants <34 weeks post conceptual age (PCA)
requiring respiratory support. This randomized clinical trial will utilize a 24 period 2
treatment crossover design to show that the device performs no worse than (non-inferiority
trial) an NICU nurse in keeping a premature neonate's SpO2 within the prescribed range while
the infant is on respiratory support. Due to the nature of the study, any masking of the
intervention is not possible. Upon enrollment, the subjects will be randomized into
enrollment in two groups (A and B). The primary endpoint will be the mean time required to
re-establish SpO2 within the prescribed range, as measured from the time an out-of-range
alarm is triggered. A secondary endpoint will be proportion of time SpO2 is within the
prescribed range, using an area-under-the-curve approach (with a discrete state) to account
for varying time-on-test. These outcome measures are complementary because the former doesn't
account for the number of alarms, while the latter does. This is important because the oxygen
control device operates continuously in a proactive manner, rather than only reacting due
alarms, so it is doing more than mimicking the nurse -- the second measure allows us to
capture that.
Group A will initially have the automatic device interface with HFNC for 6 hours. The device
will have the target SpO2 parameters ordered by the treating physician input into the device.
A study laptop will interface with the device, cardiopulmonary monitor, and pulse oximeter to
record the data for the study. Sensors will be used to record all adjustments to the
device/respiratory support equipment (i.e. blend valve and flow valve used in HFNC). These
sensors will continuously record the data for later analysis. The device will constantly
evaluate data sent to it from the pulse oximeter and bedside monitor recording all of the
data and alarms. In response to alarms, displayed data, doctor's orders, etc., nurses will
continue to apply manual inputs to make adjustments to flow and provide tactile stimulus to
the subject but not adjust FiO2 unless manual mode is selected. Recorded sensor measurements
and manual inputs by the nurse will be used to refine the existing models as well as new
models of response in HR, RR, and SpO2 to flow adjustments and tactile stimulus.
After the first 6 hours, the device will be switched to manual mode for the subject (nurse
makes all adjustments for FiO2), but the laptop and sensor data logging system will continue
to record data from the patient and the respiratory support equipment. This will record the
information for the nurse intervention/baseline care part of the study, which continue for 6
hours. During the entire process, the bedside nurse will keep a diary of any
events/interventions using the time prominently displayed on the monitoring laptop. This
"time-stamped" diary system will allow for easier retrieval of and comparison to the data
from the device and monitoring laptop. Also, the monitoring laptop will have a record of all
the data, including alarms from the pulse oximeter as well as the bedside monitor to allow
for easier retrieval of data related to alarm events and interventions. The laptop will also
record any interventions made by the device to allow for easier retrieval of data related to
device interventions. The treatment will then alternate periods of each treatment for a total
of 6 days (24 6-hour periods).
Group B will have the exact opposite order as group A. Group B infants will initially have
the laptop interface with all of the monitors and sensor measurements. However, the nurse
intervention/baseline care stage of the study will take place for the first 6 hours. Next,
group B will have the device interface with their respiratory equipment, and the data will be
recorded as described above for the next 6 hours of the study. The the treatment will
alternate every 6 hours for a total of 6 days.
This design was chosen because the premature infants should have fewer events as they grow
older each day, and it will help take into account this potential bias. Also, the subjects
will be randomized to group A or B in sets of 8 (i.e. in each group of 8 envelopes, 4 will be
group A and 4 will be group B). During the entire study process the infants will receive
normal NICU care and the parameters for the SpO2 range will be set by the physician caring
for the infant. There are also built in manual overrides for the device which allow the NICU
to make changes while the subject is on the device phase of the study. The device will be
able to record these changes and the staff will record their manual interventions in the
study diary.
We have planned our sample size using a non-inferiority test for a cross-over design, based
on our primary endpoint, t_delta. For a given patient, define t_delta = (mean elapsed time
needed for device to re-establish SpO2 after alarm) - (mean elapsed time needed for nurse to
re-establish SpO2 after alarm). The margin of non- inferiority will be chosen as t_delta >
-10 sec, so that a device which is no worse than 10 sec, on average, than a nurse will be
considered non-inferior. Assuming the standard deviation of t_delta =12 and the true mean
difference is zero under the alternate hypothesis, a sample size of 48 achieves 88% with
alpha=0.05. If there is 16% patient drop-out before crossover, so that the final n=40, the
power drops to 82%. In all analysis, a (paired) t-test will be used. Our secondary endpoint
is secondary endpoint is the proportion of time SpO2 is within the prescribed range, using an
area-under-the-curve approach (with a discrete state) to account for varying time-on-test.
Our secondary endpoint will be analyzed in a similar manner.
We will plan for one interim analysis to determine if the trial should be stoopped early due
to futility (strong evidence of inferiority, where a confidence interval for t_delta lies
entirely to the left of -10 and doesn't intersect -10) or for efficacy (strong evidence of
superiority with margin > +20 sec). This will be carried out when n=32 (16 subjects per site)
is attained and stopping decisions will be based on O'Brien-Fleming stopping principles. The
interim analysis will be carried out by an independent statistician on the University of
Missouri's Data Safety and Monitoring Committee, which is also available to monitor the study
for adverse events if requested by the IRB. In the event that the patient drop-out is greater
than 16% before crossover, then a more complicated estimation procedure will be employed
using mixed effects models; otherwise, complete cases will be used.
