Clinical trial NCT00443599: SPECS: Safe Pediatric Euglycemia in Cardiac Surgery
Official title: Maintaining Normal Blood Sugar Levels in Children Undergoing Heart Surgery to Reduce the Risk of Infections and Improve Recovery (The SPECS Study)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Heart Defects, Congenital
Hyperglycemia
Keywords: Congenital Heart Defects
Insulin
Euglycemia
Normoglycemia
Lead sponsor: Boston Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2007-03-06
Enrollment: 989
Sex: ALL
Maximum age (years): 36
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Incidence of Nosocomial Infections in the Cardiac ICU
timeFrame: Measured during participant's ICU stay, a median duration of 3 days.
Secondary outcomes:
measure: Cardiac Index (CI)
timeFrame: Day 2 (day after cardiopulmonary bypass surgery).
measure: Duration of ICU Stay
timeFrame: 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.
measure: Duration of Hospital Stay
timeFrame: 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.
measure: Duration of Endotracheal Intubation
timeFrame: 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.
measure: Mortality at Hospital Discharge.
timeFrame: 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).
measure: Mortality at 30 Days.
timeFrame: Measured at 30 days.
measure: Cardiac Function
timeFrame: 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.
measure: Immune Function
timeFrame: Post-operative day 7.
measure: Endocrine Function
timeFrame: Measured during participant's ICU stay on Day 7.
measure: Nutritional Status
timeFrame: 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.
measure: Neurodevelopmental Evaluation, Cognitive
timeFrame: Measured at one year of age.
measure: Neurodevelopmental Evaluation, Language
timeFrame: Measured at one year of age.
measure: Neurodevelopmental Evaluation, Motor
timeFrame: Measured at one year of age.
Other outcomes:
Locations:
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Ann Arbor
country: United States
facility: C.S. Mott Children's Hospital
state: Michigan
Study officials:
affiliation: Boston Children's Hospital
name: Michael Agus, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Agus MS, Javid PJ, Piper HG, Wypij D, Duggan CP, Ryan DP, Jaksic T. The effect of insulin infusion upon protein metabolism in neonates on extracorporeal life support. Ann Surg. 2006 Oct;244(4):536-44. doi: 10.1097/01.sla.0000237758.93186.c8.
citation: Piper HG, Alexander JL, Shukla A, Pigula F, Costello JM, Laussen PC, Jaksic T, Agus MS. Real-time continuous glucose monitoring in pediatric patients during and after cardiac surgery. Pediatrics. 2006 Sep;118(3):1176-84. doi: 10.1542/peds.2006-0347.
citation: Javid PJ, Halwick DR, Betit P, Thompson JE, Long K, Zhang Y, Jaksic T, Agus MS. The first use of live continuous glucose monitoring in patients on extracorporeal life support. Diabetes Technol Ther. 2005 Jun;7(3):431-9. doi: 10.1089/dia.2005.7.431.
citation: Agus MS, Javid PJ, Ryan DP, Jaksic T. Intravenous insulin decreases protein breakdown in infants on extracorporeal membrane oxygenation. J Pediatr Surg. 2004 Jun;39(6):839-44; discussion 839-44. doi: 10.1016/j.jpedsurg.2004.02.013.
citation: Gaies MG, Langer M, Alexander J, Steil GM, Ware J, Wypij D, Laussen PC, Newburger JW, Goldberg CS, Pigula FA, Shukla AC, Duggan CP, Agus MS; Safe Pediatric Euglycemia after Cardiac Surgery Study Group. Design and rationale of safe pediatric euglycemia after cardiac surgery: a randomized controlled trial of tight glycemic control after pediatric cardiac surgery. Pediatr Crit Care Med. 2013 Feb;14(2):148-56. doi: 10.1097/PCC.0b013e31825b549a.
citation: Agus MS, Steil GM, Wypij D, Costello JM, Laussen PC, Langer M, Alexander JL, Scoppettuolo LA, Pigula FA, Charpie JR, Ohye RG, Gaies MG; SPECS Study Investigators. Tight glycemic control versus standard care after pediatric cardiac surgery. N Engl J Med. 2012 Sep 27;367(13):1208-19. doi: 10.1056/NEJMoa1206044. Epub 2012 Sep 7.
citation: Sadhwani A, Asaro LA, Goldberg CS, Ware J, Butcher J, Gaies M, Smith C, Alexander JL, Wypij D, Agus MSD. Impact of tight glycemic control and hypoglycemia after pediatric cardiac surgery on neurodevelopmental outcomes at three years of age: Findings from a randomized clinical trial. BMC Pediatr. 2022 Sep 7;22(1):531. doi: 10.1186/s12887-022-03556-z.
citation: Sadhwani A, Asaro LA, Goldberg C, Ware J, Butcher J, Gaies M, Smith C, Alexander JL, Wypij D, Agus MS. Impact of Tight Glycemic Control on Neurodevelopmental Outcomes at 1 Year of Age for Children with Congenital Heart Disease: A Randomized Controlled Trial. J Pediatr. 2016 Jul;174:193-198.e2. doi: 10.1016/j.jpeds.2016.03.048. Epub 2016 Apr 23.
citation: Fisher JG, Sparks EA, Khan FA, Alexander JL, Asaro LA, Wypij D, Gaies M, Modi BP, Duggan C, Agus MS, Yu YM, Jaksic T. Tight Glycemic Control With Insulin Does Not Affect Skeletal Muscle Degradation During the Early Postoperative Period Following Pediatric Cardiac Surgery. Pediatr Crit Care Med. 2015 Jul;16(6):515-21. doi: 10.1097/PCC.0000000000000413.
citation: Agus MS, Asaro LA, Steil GM, Alexander JL, Silverman M, Wypij D, Gaies MG; SPECS Investigators. Tight glycemic control after pediatric cardiac surgery in high-risk patient populations: a secondary analysis of the safe pediatric euglycemia after cardiac surgery trial. Circulation. 2014 Jun 3;129(22):2297-304. doi: 10.1161/CIRCULATIONAHA.113.008124. Epub 2014 Mar 26.