Maintaining Optimal HVNI Delivery Using Automatic Titration of Oxygen in Preterm Infants

NCT ID: NCT05030012

Last Updated: 2024-06-26

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: NA
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-02
• Study Completion Date: 2023-10-19

Brief Summary

Oxygen treatment is common in management of preterm babies requiring intensive care. Delivery of too much or too little oxygen increase the risk of damage to eyes and lungs, and contributes to death and disability. Oxygen control in preterm infants requires frequent adjustments in the amount of oxygen delivered to the baby. This is generally performed manually by a clinician attending the baby, and generally directed to maintaining a specific range of blood oxygen saturation. The manual control often results in only half of the time in the specified range, with the baby experiencing high and low blood oxygen saturations.

The technology being studied is designed to assist the clinician in maintaining blood oxygen saturation within target range by measuring oxygen saturation and automatically adjusting the amount of oxygen delivered for babies receiving high velocity nasal insufflation (an advanced form of high flow oxygen therapy). The proposed study will evaluate the efficacy and safety of the automatic control of oxygen by the new technology, as compared to manual control, among babies receiving high velocity therapy in a neonatal intensive care unit.

Detailed Description

Detailed Description: Supplemental oxygen is commonly administered to babies in neonatal intensive care units. The goal of oxygen therapy is to maintain normal oxygenation while minimizing hypoxemia and hypoxemia. Preterm infants are particularly vulnerable to oxygen toxicity and oxidative stress leading to retinopathy of prematurity (ROP), bronchopulmonary dysplasia (BPD), and periventricular leukomalacia (PVL). It's also well known that preterm infants experience hypoxic events exposing the baby to low oxygen levels. These hypoxic events vary as the infant matures, but exposure to prolonged and frequent episodes of hypoxemia is associated with increased morbidity and mortality. The delivery of oxygen is generally controlled by a clinician, and the control decisions are generally made using a non-invasive measure of blood oxygen saturation called pulse oximetry (SpO2) and is a standard of care in the neonatal intensive care unit. The most frequent item adjusted by clinicians to maintain SpO2 within specific target ranges is the fraction of the inspired oxygen (FiO2).

In a recent study by Reynolds, et al., caregiver manual control of oxygen delivered to NICU babies receiving high velocity therapy resulted in only 49% of the total 24-hour study period with the babies within the target SpO2 range (90-95%). by the caregiver based on the monitored oxygen saturation. Similar to the Reynolds findings, Hagadorn et al., conducted a study in 14 centers and showed that preterm infants under 28 weeks' gestation receiving oxygen spent on average only 48% of the time with SpO2 within the prescribed target range, about 36% of the time above and 16% of the time with SpO2 below the target range.

Preterm infants have frequent fluctuations in SpO2 due to their cardio-respiratory instability requiring frequent adjustments of FiO2 . Consequently, these particularly vulnerable infants spend significant time with SpO2 outside the optimal target range and are often exposed to extremes of hypoxemia and hyperoxaemia. The automatic oxygen control system continuously monitors the oxygen saturation and adjusts the oxygen delivery to maintain oxygen saturation within the target range. The efficacy of this mode of oxygen control was demonstrated by Reynolds, et al. in 2018 from two centers in the United Kingdom. Automated control of FiO2 can significantly improve compliance of oxygen saturation targeting and may significantly reduces exposure to hypoxemia as well as hyperoxaemia. The high velocity nasal insufflation therapy is a common mode of non-invasive respiratory support in preterm infants.

Unlike prior studies, this study will include a set of hypothesis-driven safety endpoints (proportion of time above or below target range), stratification by body mass at enrolment, and skin pigmentation phenotype. The objective of this randomized control trial is to evaluate the efficacy of the controller (Vapotherm Oxygen Assist Module [OAM]) in maintaining the SpO2 within target range for premature infants receiving high velocity therapy and presenting with a labile FiO2 requirement.

Conditions

Infant, Premature; Neonatal Respiratory Distress; Oxygen Saturation; Bronchopulmonary Dysplasia

Study Design

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

Study Groups

Automated Control (OAM)

In this arm, FiO2 levels delivered via high-velocity nasal insufflation therapy (Vapotherm Precision Flow) will be adjusted by the Oxygen Assist Module (OAM) to keep the infants pulse oxygen saturation within a target range (90-95%). Clinical staff will have the ability to override FiO2 levels when required, and instructed to do so.

Group Type: EXPERIMENTAL

Automated Control

Intervention Type: DEVICE

The purpose of this intervention is to evaluate that the efficacy and safety during the automated performance of the Vapotherm OAM are not inferior to standard care practice (manual control) in maintaining SpO2 levels of 90-95% in preterm infants requiring oxygen adjustments while being treated with high velocity nasal insufflation (HVNI) therapy.

Manual Control (Manual)

In this arm, FiO2 levels delivered via high-velocity nasal insufflation therapy (Vapotherm Precision Flow) will be manually adjusted by clinical staff to keep infants' oxygen saturation between 90-95%.

Group Type: ACTIVE_COMPARATOR

Manual Control

Intervention Type: DEVICE

The purpose of this intervention is to establish an active comparator via standard care practice against which to evaluate the efficacy and safety of the automated arm of the study, for determination of non-inferiority of that automated control arm to manual control in maintaining SpO2 levels of 90-95% in preterm infants being treated with high velocity nasal insufflation (HVNI) therapy.

Interventions

Automated Control

The purpose of this intervention is to evaluate that the efficacy and safety during the automated performance of the Vapotherm OAM are not inferior to standard care practice (manual control) in maintaining SpO2 levels of 90-95% in preterm infants requiring oxygen adjustments while being treated with high velocity nasal insufflation (HVNI) therapy.

Intervention Type: DEVICE

Manual Control

The purpose of this intervention is to establish an active comparator via standard care practice against which to evaluate the efficacy and safety of the automated arm of the study, for determination of non-inferiority of that automated control arm to manual control in maintaining SpO2 levels of 90-95% in preterm infants being treated with high velocity nasal insufflation (HVNI) therapy.

Intervention Type: DEVICE

Other Intervention Names

Oxygen Assist Module (OAM); Vapotherm OAM + Vapotherm Precision Flow; Vapotherm Precision Flow; Treatment as Usual (TAU); Standard of Care (SOC)

Eligibility Criteria

Inclusion Criteria

1. Infants delivered at a gestational age of less than or equal to 35 6/7 weeks (Preterm) being treated with high velocity nasal insufflation therapy for the management of respiratory distress syndrome

2. Patients that clinically require SpO2 maintenance within the target range of 90-95%

3. A need for supplemental oxygen as demonstrated by a required FiO2 > 0.25 at enrollment

4. Requiring a flow rate of greater than 2 L•min-1 such that the assumed inspired oxygen fraction matched delivered oxygen fraction (definition of HVNI).

5. A minimum of 6 manual FiO2 adjustments in the 24hr period prior to trial enrollment.

6. Willing/Able to complete informed consent.

Exclusion Criteria

1. Current patient weight of <1000g or >3500g at time of study

2. Major congenital abnormalities

3. Hemodynamic instability, defined as being outside of a normotensive range based on an infant's individual characteristics by clinician

4. Persistent unresolved apnea defined as: requiring 6 stimulations or more per 6 hours

5. Seizures

6. Ongoing sepsis

7. Meningitis

8. Clinician's concern regarding stability of the infant

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Children's National Research Institute

OTHER

Sponsor Role: collaborator

Seattle Children's Hospital

OTHER

Sponsor Role: collaborator

University of Utah

OTHER

Sponsor Role: collaborator

Vapotherm, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Billie L Short, MD

Role: PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Khodayar Rais-Bahrami, MD

Role: PRINCIPAL_INVESTIGATOR

Children's National Research Institute

Robert J DiGeronimo, MD

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Robert DiBlasi, RRT-NPS

Role: PRINCIPAL_INVESTIGATOR

Seattle Children's Hospital

Bradley A Yoder, MD

Role: PRINCIPAL_INVESTIGATOR

University of Utah Hospital

Locations

Children's National Hospital & Research Institute

Washington D.C., District of Columbia, United States

University of Utah Hospital

Salt Lake City, Utah, United States

Seattle Children's Hospital

Seattle, Washington, United States

Countries

United States

References

Reynolds PR, Miller TL, Volakis LI, Holland N, Dungan GC, Roehr CC, Ives K. Randomised cross-over study of automated oxygen control for preterm infants receiving nasal high flow. Arch Dis Child Fetal Neonatal Ed. 2019 Jul;104(4):F366-F371. doi: 10.1136/archdischild-2018-315342. Epub 2018 Nov 21.

Reference Type: BACKGROUND

PMID: 30464005 (View on PubMed)

Hagadorn JI, Furey AM, Nghiem TH, Schmid CH, Phelps DL, Pillers DA, Cole CH; AVIOx Study Group. Achieved versus intended pulse oximeter saturation in infants born less than 28 weeks' gestation: the AVIOx study. Pediatrics. 2006 Oct;118(4):1574-82. doi: 10.1542/peds.2005-0413.

Reference Type: BACKGROUND

PMID: 17015549 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

RP-NIOA2019001Reg

Identifier Type: -

Identifier Source: org_study_id