NICU Oxygen Control Study

NCT ID: NCT04269161

Last Updated: 2025-07-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 48 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-05-24
• Study Completion Date: 2024-06-06

Brief 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.

Detailed 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 stopped 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.

Conditions

Hyperoxia; Hypoxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: NONE

Study Groups

Crossover Sequence 1

In this arm, an automatic oxygen control device will be used to make adjustments to the blend of oxygen and air supplied to the subject for the first six hours.

In this arm, a nurse will manually make adjustments to the blend of oxygen and air supplied to the subject for the second six hours. The study continues in an automatic and manual repeating pattern for six days.

Group Type: EXPERIMENTAL

Automatic control of inspired oxygen

Intervention Type: DEVICE

A device will be used to automatically adjust the blend of oxygen and air with the ability to return to manual control as needed.

Crossover Sequence 2

In this arm, a nurse will manually make adjustments to the blend of oxygen and air supplied to the subject as in the standard of care for the first six hours.

In this arm, an automatic oxygen control device will be used to make adjustments to the blend of oxygen and air supplied to the subject for the second six hours. The study continues in a manual and automatic repeating pattern for six days.

Group Type: EXPERIMENTAL

Automatic control of inspired oxygen

Intervention Type: DEVICE

A device will be used to automatically adjust the blend of oxygen and air with the ability to return to manual control as needed.

Interventions

Automatic control of inspired oxygen

A device will be used to automatically adjust the blend of oxygen and air with the ability to return to manual control as needed.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Infants admitted to the NICU
• Less than 31 weeks estimated gestational age or less than 1500 grams at birth
• Currently on high flow nasal cannula or bubble CPAP
• Require at least 2 adjustments to the FiO2 per shift and/or have at least 2 desaturation events per shift

Exclusion Criteria

• Infants admitted to the NICU with congenital heart disease.
• Infants who are set on a minimum FiO2 set point by their healthcare provider

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sacred Heart Health System

OTHER

Sponsor Role: collaborator

University of Missouri-Columbia

OTHER

Sponsor Role: lead

Responsible Party

Roger C Fales

Associate Professor of Mechanical and Aerospace Engineering

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

John A Pardalos, MD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Ramak R Amjad, MD

Role: PRINCIPAL_INVESTIGATOR

Studer Family Children's Hospital at Sacred Heart

Roger C Fales, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Missouri-Columbia

Locations

Studer Family Children's Hospital at Sacred Heart

Pensacola, Florida, United States

University of Missouri

Columbia, Missouri, United States

Countries

United States

References

Hou X, Faqeeh A, Amjad R, Pardalos J, Fales R. Clinical Evaluation of an Automatic Oxygen Control System for Premature Infants Receiving High-Flow Nasal Cannula for Respiratory Support: A Pilot Study. J Med Device. 2022 Sep 1;16(3):031005. doi: 10.1115/1.4054250. Epub 2022 May 10.

Reference Type: BACKGROUND

PMID: 35646226 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Document Type: Informed Consent Form: Consent 1, Missouri

View Document

Document Type: Informed Consent Form: Consent 2, Florida

View Document

Other Identifiers

2003117

Identifier Type: -

Identifier Source: org_study_id