Hypoglycemia, Newborn Morbidity
Conditions
Brief summary
Our aim is to determine the feasibility of using continuous glucose monitors (CGMs) in infants with low blood glucose to improve how we care for these infants. To do this we plan on monitoring blood glucose levels with CGMs (instead of only with intermittent bloodsampling) in late-preterm and term infants admitted to the NICU who have had hypoglycemia. To see if using CGMs helps us prevent low blood glucose levels and allows us to find a diagnosis and treat sooner, we will randomize patients into one of two groups: a CGM group where the CGM information is made available to the NICU team and a Standard of Care group where the CGM information will only be available to the research team. However, if infants in the Standard of Care group are noted to have three unrecognized severe low blood glucose levels then the research team will inform the NICU team that this has occurred.
Detailed description
We aim to evaluate the utility of continuous glucose monitors (CGMs) in improving the diagnosis and management of neonatal hypoglycemia in infants admitted to the neonatal intensive care unit (NICU). Specifically, we hope to assess whether the use of CGMs in this population reduces the number and severity of hypoglycemic events, reduces the time to diagnosis of the etiology of hypoglycemia and/or reduces the time taken to achieve stable euglycemia on a sustainable feeding regimen. We plan to perform a prospective pilot and feasibility study comparing the clinical course and outcomes of newborns with hypoglycemia admitted to the NICU who are actively monitored with CGMs versus those who receive routine care. Eligible infants will be late preterm and term infants admitted to the Boston Children's Hospital who have had two documented hypoglycemic episodes during their current admission. Families will be approached for consent shortly after diagnosis of recurrent hypoglycemia. As all of these infants will be undergoing periodic blood glucose monitoring as part of their routine care, enrollment in this study will involve minimal additional interventions, including CGM placement, which involves placement of a small subcutaneous needle sensor, and the possibility of drawing additional blood glucose samples if hypoglycemia is detected by CGM. All enrolled infants will be placed on a CGM monitor and then randomized to either the CGM Protocol or Standard of Care group. Those on the CGM Protocol will have a fully accessible CGM that will be analyzed for blood glucose trends and will alarm for any blood glucose level approaching hypoglycemic threshold (eg. BG \<70 mg/dL). Those in the Standard of Care group will have a CGM in place, but values will not be available to the clinical team except if severe hypoglycemia is recorded (eg. BG \<40 mg/dL). Whenever the CGM alarms or there is a concerning blood glucose trend as measured by the CGM, the nurse will be asked to check a blood glucose value. All clinical management decisions will be made by the clinical team based on confirmed blood glucose values. In the control group, the only change to current management is the potential performance of additional blood glucose checks that may be prompted by CGM alarms for severe hypoglycemia. The CGM will remain in place until the infant is no longer being monitored for glycemic stability or the infant is discharged. We will record all blood glucose levels, laboratory data related to investigation of the underlying cause of hypoglycemia, all intravenous and enteral sources of glucose, and uses of other therapeutic interventions such as diazoxide and carnitine replacement. We will also compare blood glucose data with information from the CGM monitors to assess accuracy. We will then compare severity and frequency of hypoglycemia, as well as times to diagnosis and euglycemia between the CGM and Standard of Care groups.
Interventions
DEVICEContinuous Glucose Monitoring
Continuous glucose monitors (CGM) will be used to monitor blood sugar levels in enrolled subjects. CGMs measure blood sugar in the tissue just under the skin every few seconds and report average blood sugar every 5 minutes. In our study, the CGMs will function as monitoring systems. In the CGM protocol group the CGM will let the medical team know if there is a concerning blood sugar level, so that the medical team can then check a blood sugar level by the standard way (usually in a small drop of blood) and then decide if they need to give any medical treatment. In the Standard of Care group the CGM data will not be visible to the medical team but the medical team will be informed by the researchers if there are multiple unrecognized episodes of severe hypoglycemia.
Sponsors
Boston Children's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
DIAGNOSTIC
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
No minimum to 60 Days
Healthy volunteers
No
Inclusion criteria
* Age 0-60 days old * Late-preterm and term infants (babies born more than 33 weeks and 6 days after the start of the pregnancy) * History of low blood sugars (hypoglycemia): two episodes of hypoglycemia more than 1 hour apart (low blood sugar will be defined by age: for those less than 48 hours old a low blood sugar is considered less than 50mg/dL and for those older than 48 hours old less than 70mg/dL)
Exclusion criteria
* Infants with skin disease such that placement of a glucose sensor under the skin would be difficult to secure * Infants expected to remain in NICU less than 24 hours * Infants on a hypothermic protocol * Infants enrolled in a competing clinical trial * Family/team have decided to limit or redirect from aggressive NICU technological support * infants who are wards of the state
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Frequency of Hypoglycemic Events | Up to 28 days | Hypoglycemia is defined by age group: for patients less than 48 hours of life, hypoglycemia is defined as glucose level \< 50 mg/dL for patients greater than or equal to 48 hours of life it is defined as glucose level \< 70 mg/dL. |
| Frequency of Severe Hypoglycemia Events | Up to 28 days | Severe hypoglycemia is defined as glucose level \< 40 mg/dL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Events Where Etiology of Hypoglycemia Was Established | up tp 28 days | Diagnosis of the etiology of hypoglycemia, and the time to to do, will be evaluated in order to determine if the use of CGM will prompt earlier testing to evaluate the etiology of the hypoglycemia and therefore lead to earlier ascertainment of the underlying etiology. Diagnosis of etiology. |
| Time to Diagnosis of Etiology of Hypoglycemia | Up to 28 days | Diagnosis of the etiology of hypoglycemia, and the time to to do, will be evaluated in order to determine if the use of CGM will prompt earlier testing to evaluate the etiology of the hypoglycemia and therefore lead to earlier ascertainment of the underlying etiology. Time to diagnosis of etiology. |
| Time to Stable Euglycemia | Up to 28 days | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| CGM Protocol Subjects will receive continuous glucose monitoring and caregivers will be able to view continuous glucose measurements.
Continuous Glucose Monitoring: Continuous glucose monitors (CGM) will be used to monitor blood sugar levels in enrolled subjects. CGMs measure blood sugar in the tissue just under the skin every few seconds and report average blood sugar every 5 minutes. In our study, the CGMs will function as monitoring systems. In the CGM protocol group the CGM will let the medical team know if there is a concerning blood sugar level, so that the medical team can then check a blood sugar level by the standard way (usually in a small drop of blood) and then decide if they need to give any medical treatment. | 3 |
| Standard of Care Subjects will receive continuous glucose monitoring but caregivers will not be able to view continuous glucose measurements.
Continuous Glucose Monitoring: Continuous glucose monitors (CGM) will be used to monitor blood sugar levels in enrolled subjects. CGMs measure blood sugar in the tissue just under the skin every few seconds and report average blood sugar every 5 minutes. In our study, the CGMs will function as monitoring systems. In the Standard of Care group the CGM data will not be visible to the medical team but the medical team will be informed by the researchers if there are multiple unrecognized episodes of severe hypoglycemia. | 3 |
| Total | 6 |
Baseline characteristics
| Characteristic | Standard of Care | Total | CGM Protocol |
|---|---|---|---|
| Age, Continuous | 3.33 Days | 3.17 Days | 3.0 Days |
| Race and Ethnicity Not Collected | — | 0 Participants | — |
| Region of Enrollment United States | 3 participants | 6 participants | 3 participants |
| Sex: Female, Male Female | 2 Participants | 4 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 3 | 0 / 3 |
| other Total, other adverse events | 0 / 3 | 0 / 3 |
| serious Total, serious adverse events | 0 / 3 | 0 / 3 |
Outcome results
Primary
Frequency of Hypoglycemic Events
Hypoglycemia is defined by age group: for patients less than 48 hours of life, hypoglycemia is defined as glucose level \< 50 mg/dL for patients greater than or equal to 48 hours of life it is defined as glucose level \< 70 mg/dL.
Time frame: Up to 28 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CGM Protocol | Frequency of Hypoglycemic Events | 14 Events | Standard Deviation 2 |
| Standard of Care | Frequency of Hypoglycemic Events | 19 Events | Standard Deviation 3 |
Primary
Frequency of Severe Hypoglycemia Events
Severe hypoglycemia is defined as glucose level \< 40 mg/dL
Time frame: Up to 28 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGM Protocol | Frequency of Severe Hypoglycemia Events | 1 Events |
| Standard of Care | Frequency of Severe Hypoglycemia Events | 4 Events |
Secondary
Number of Events Where Etiology of Hypoglycemia Was Established
Diagnosis of the etiology of hypoglycemia, and the time to to do, will be evaluated in order to determine if the use of CGM will prompt earlier testing to evaluate the etiology of the hypoglycemia and therefore lead to earlier ascertainment of the underlying etiology. Diagnosis of etiology.
Time frame: up tp 28 days
Population: Events of diagnosis of hyperinsulinemic hypoglycemia
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| CGM Protocol | Number of Events Where Etiology of Hypoglycemia Was Established | 2 Events |
| Standard of Care | Number of Events Where Etiology of Hypoglycemia Was Established | 1 Events |
Secondary
Time to Diagnosis of Etiology of Hypoglycemia
Diagnosis of the etiology of hypoglycemia, and the time to to do, will be evaluated in order to determine if the use of CGM will prompt earlier testing to evaluate the etiology of the hypoglycemia and therefore lead to earlier ascertainment of the underlying etiology. Time to diagnosis of etiology.
Time frame: Up to 28 days
| Arm | Measure | Value (MEAN) |
|---|---|---|
| CGM Protocol | Time to Diagnosis of Etiology of Hypoglycemia | 1.5 Days |
| Standard of Care | Time to Diagnosis of Etiology of Hypoglycemia | 4 Days |
Secondary
Time to Stable Euglycemia
Time frame: Up to 28 days
Population: Patients did not remain on protocol until euglycemia was reached, therefore no data was collected for this Outcome Measure.