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

Sponsor

Vapotherm, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT05030012

Collaborator

Children's National Research Institute (Other), Seattle Children's Hospital (Other), University of Utah (Other)

Enrollment

Locations

Arms

10.2

Anticipated Duration (Months)

15.7

Patients Per Site

1.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Infant, Premature Neonatal Respiratory Distress Oxygen Saturation Bronchopulmonary Dysplasia	Device: Automated Control Device: Manual Control	N/A

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

47 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

Intervention Model Description:

This study will be a prospective, multi-center, randomized, crossover trial evaluating automated oxygen titration versus manual titration in maintaining oxygen saturation levels in preterm infants requiring noninvasive ventilatory support via high velocity nasal insufflation (HVNI).This study will be a prospective, multi-center, randomized, crossover trial evaluating automated oxygen titration versus manual titration in maintaining oxygen saturation levels in preterm infants requiring noninvasive ventilatory support via high velocity nasal insufflation (HVNI).

Masking:

None (Open Label)

Masking Description:

This study is unblinded, as there is a distinct difference in modality control between automated and manual modes. Clinical staff are instructed to perform FiO2 adjustments as required, regardless of the study arm.

Primary Purpose:

Treatment

Official Title:

Maintaining Optimal Delivery Using Automatic Titration of Oxygen in Preterm Infants Receiving High Velocity Nasal Insufflation Therapy

Actual Study Start Date :

Aug 23, 2021

Anticipated Primary Completion Date :

Mar 31, 2022

Anticipated Study Completion Date :

Jun 30, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 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.	Device: 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. Other Names: Oxygen Assist Module (OAM) Vapotherm OAM + Vapotherm Precision Flow
Active Comparator: 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%.	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. Other Names: Vapotherm Precision Flow Treatment as Usual (TAU) Standard of Care (SOC)

Arm

Intervention/Treatment

Experimental: 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.

Device: 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.

Other Names:

Oxygen Assist Module (OAM)

Vapotherm OAM + Vapotherm Precision Flow

Active Comparator: 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%.

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.

Other Names:

Vapotherm Precision Flow

Treatment as Usual (TAU)

Standard of Care (SOC)

Outcome Measures

Primary Outcome Measures

Primary Safety Objective - Proportion of Time Outside of SpO2 Target Range [Through study completion, two consecutive 24-hour periods]
Percentage of time spent outside target oxygen saturation range, measured by pulse oximetry (SpO2). A lower value indicates a better outcome.
Primary Performance Objective - Proportion of Time Within SpO2 Target Range [Through study completion, two consecutive 24-hour periods]
Percentage of time spent within target oxygen saturation range, measured by pulse oximetry (SpO2). A higher value indicates a better outcome.

Secondary Outcome Measures

Secondary Performance Objective 1 - Proportion of Time Within SpO2 Target Range (Weight Groups) [Through study completion, two consecutive 24-hour periods]
Percentage of time spent within target oxygen saturation range across two weight groups (1000-1500g, 1500-2500g), measured by pulse oximetry (SpO2). A higher value indicates a better outcome.
Secondary Performance Objective 2 - Proportion of Time Within SpO2 Target Range (Skin Pigmentation) [Through study completion, two consecutive 24-hour periods]
Percentage of time spent within target oxygen saturation range across two skin pigmentation groups (light, dark), measured by pulse oximetry (SpO2). A higher value indicates a better outcome.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Preterm infants being treated with high velocity nasal insufflation therapy
Patients that clinically require SpO2 maintenance within the target range of 90-95%
A need for supplemental oxygen as demonstrated by a required FiO2 > 0.25 at enrollment
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).
A minimum of 12 manual FiO2 adjustments in the 24hr period prior to trial enrollment.
Parents willing/able to complete informed consent.

Exclusion Criteria:

Current patient weight of <1000g or >2500g at time of study
Major congenital abnormalities
Hemodynamic instability, defined as being outside of a normotensive range based on an infant's individual characteristics by clinician
Persistent unresolved apnea defined as: requiring 6 stimulations or more per 6 hours
Seizures
Ongoing sepsis
Meningitis
Clinician's concern regarding stability of the infant

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children's National Hospital & Research Institute	Washington	District of Columbia	United States	20010
2	University of Utah Hospital	Salt Lake City	Utah	United States	84132
3	Seattle Children's Hospital	Seattle	Washington	United States	98195

Sponsors and Collaborators

Vapotherm, Inc.
Children's National Research Institute
Seattle Children's Hospital
University of Utah

Investigators

Principal Investigator: Billie L Short, MD, Children's National Research Institute
Principal Investigator: Khodayar Rais-Bahrami, MD, Children's National Research Institute
Principal Investigator: Robert J DiGeronimo, MD, Seattle Children's Hospital
Principal Investigator: Robert DiBlasi, RRT-NPS, Seattle Children's Hospital
Principal Investigator: Bradley A Yoder, MD, University of Utah Hospital