SPECS: Safe Pediatric Euglycemia in Cardiac Surgery

Study Overview
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Brief Summary
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Critically ill children, including children undergoing heart surgery, commonly develop elevated blood glucose (also known as blood sugar) levels during their illness, which can lead to poor health outcomes and an increased risk of death. This study will examine the effectiveness of maintaining normal blood glucose levels at decreasing infections and improving recovery in young children undergoing heart surgery.

Detailed Description
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Children undergoing heart surgery are under significant bodily stress, which can lead to higher than normal or lower than normal blood glucose levels. A synthetic form of insulin, a naturally occurring hormone in the body, can be injected into people to normalize blood glucose levels. Insulin is most commonly used to treat people with diabetes, but it is also used in hospitals to control blood glucose levels in patients. Previous studies of adult intensive care unit (ICU) patients have shown that patients whose blood sugar levels are maintained at normal levels with the use of insulin contract fewer infections and are released more quickly from the ICU than patients who do not maintain normal blood glucose levels. This study will use a continuous blood glucose monitoring system to detect changes in blood glucose levels. Intravenous insulin infusions will be used to then safely maintain normal blood glucose levels. The purpose of this study is to determine if maintaining normal blood glucose levels during an ICU stay will help decrease the incidence of infections and improve surgical recovery in young children following heart surgery. This study will enroll children who are undergoing heart surgery that requires a cardiopulmonary bypass procedure. Participants will be randomly assigned to either a control group or the treatment group. All participants will receive usual care while in the ICU and will undergo continuous glucose monitoring. Participants in the treatment group will receive intravenous insulin infusions to keep their blood glucose within the normal range. While in the ICU, blood will be collected from all participants once a day for the first 3 days and then once a week to monitor glucose levels, hormone levels, and measurements of nutrition and immune function. On days 1 and 5 following surgery, participants who are on a ventilator will have their breath measured to monitor heart function and energy use. Thirty days and 1 year following surgery, study researchers will contact the participant's parent or doctor to collect information on health status and any new infections at the surgical site. Children who enroll in the study will be asked to participate in follow-up neurodevelopmental evaluations at 1 and 3 years of age to assess longer term cognitive effects of tight glycemic control in the ICU.

Official Title
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Maintaining Normal Blood Sugar Levels in Children Undergoing Heart Surgery to Reduce the Risk of Infections and Improve Recovery (The SPECS Study)

Conditions
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Heart Defects, Congenital, Hyperglycemia

Intervention / Treatment
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* Drug: Insulin
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Undergoing heart surgery with cardiopulmonary bypass Recovering in the Cardiac ICU Exclusion Criteria: Enrolled in another interventional clinical trial with related study outcomes

Ages Eligible for Study
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Maximum Age: 36 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Insulin<br>Insulin was infused to target a blood glucose concentration of 80-110 mg/dL | Drug: Insulin<br>* Study drug is continuously infused intravenous insulin. Suggested dose is calculated by a computerized infusion algorithm using the participant's blood sugar concentration. The insulin infusion rate is titrated to maintain normal blood sugar. Participants are eligible to receive insulin while they have an in-dwelling arterial catheter.<br>* Other names: Novolin R;|
| Active Comparator: Usual Care<br>Insulin was infused according to the discretion of the treating clinical team. | Other: Usual Care<br>* Participants receive standard Cardiac ICU care without tight blood glucose control.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of Nosocomial Infections in the Cardiac ICU | Nosocomial infections that are attributable to the subject's stay in the Cardiac ICU, according to Center for Disease Control-defined criteria. These definitions are extensive and cannot be accurately condensed to fit within this space. Current CDC/NHSN criteria may be accessed through this URL: https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf. | Measured during participant's ICU stay, a median duration of 3 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cardiac Index (CI) | Cardiac index is a measure of cardiac function, relating the cardiac output from the left ventricle in one minute to body surface area. It is calculated using the Fick principle, using oxygen consumption measured with a metabolic cart, hemoglobin levels, and the difference between arterial and superior vena cava oxygen saturation measured by co-oximetry. | Day 2 (day after cardiopulmonary bypass surgery). | 
| Duration of ICU Stay | Duration of ICU stay spans from post-operative cardiac ICU admission to cardiac ICU discharge. | The duration of cardiac ICU stay was evaluated from the date of postoperative cardiac ICU admission until the date of cardiac ICU discharge or date of death from any cause, whichever came first, assessed up to 30 days. | 
| Duration of Hospital Stay | Duration of hospital stay spans from post-operative cardiac ICU admission to hospital discharge. | The duration of hospital stay was evaluated from the day of postoperative cardiac ICU admission until the day of hospital discharge or day of death from any cause, whichever came first, assessed up to 30 days. | 
| Duration of Endotracheal Intubation | Duration of endotracheal intubation spans from endotracheal tube intubation/initiation of mechanical ventilation to endotracheal tube extubation. | The duration of endotracheal intubation (mechanical ventilation) was evaluated from the day of postoperative cardiac ICU admission until the day of extubation or day of death from any cause, whichever came first, assessed up to 30 days. | 
| Mortality at Hospital Discharge. | Mortality is assessed at hospital discharge and at 30 days. | Mortality at hospital discharge (In-hospital mortality) was evaluated on the day of hospital discharge or day of death from any cause, whichever came first (no upper limit). | 
| Mortality at 30 Days. | Mortality is assessed at hospital discharge and at 30 days. If the participant is discharged from the hospital prior to 30 days, status is determined by a follow-up phone call to the family. | Measured at 30 days. | 
| Cardiac Function | Cardiac function is assessed by duration of vasoactive support. | The duration of vasoactive support was evaluated from the day of postoperative cardiac ICU admission until the last day of vasoactive support or day of death from any cause, whichever came first, assessed up to 30 days. | 
| Immune Function | Immune function is assessed by C-reactive protein (CRP) on post-operative day 7. | Post-operative day 7. | 
| Endocrine Function | Endocrine function is assessed by total triiodothyronine (T3) on post-operative day 7. | Measured during participant's ICU stay on Day 7. | 
| Nutritional Status | Nutritional status assessed by percentage of total caloric intake as enteral nutrition during critical illness period. | The percentage of total caloric intake was evaluated from the day of postoperative cardiac ICU admission until the last day of the critical illness period, as defined by the presence of the arterial catheter, assessed up to 30 days. | 
| Neurodevelopmental Evaluation, Cognitive | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age. Bayley-III cognitive composite score ranges from 55-145, Bayley-III language composite score ranges from 47-153, and Bayley-III motor composite score ranges from 46-154. Higher values indicate better neurodevelopmental outcomes. These three composite scores cannot be combined and are presented as separate scores in the literature. | Measured at one year of age. | 
| Neurodevelopmental Evaluation, Language | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age. Bayley-III cognitive composite score ranges from 55-145, Bayley-III language composite score ranges from 47-153, and Bayley-III motor composite score ranges from 46-154. Higher values indicate better neurodevelopmental outcomes. These three composite scores cannot be combined and are presented as separate scores in the literature. | Measured at one year of age. | 
| Neurodevelopmental Evaluation, Motor | Neurodevelopmental follow-up includes in-person testing using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley-III), measured at one year of age. Bayley-III cognitive composite score ranges from 55-145, Bayley-III language composite score ranges from 47-153, and Bayley-III motor composite score ranges from 46-154. Higher values indicate better neurodevelopmental outcomes. These three composite scores cannot be combined and are presented as separate scores in the literature. | Measured at one year of age. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Congenital Heart Defects, Insulin, Euglycemia, Normoglycemia