Trial Outcomes & Findings for SPECS: Safe Pediatric Euglycemia in Cardiac Surgery (NCT NCT00443599)

NCT ID: NCT00443599

Last Updated: 2022-07-25

Results Overview

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.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 989 participants
• Primary outcome timeframe: Measured during participant's ICU stay, a median duration of 3 days.
• Results posted on: 2022-07-25

Participant Flow

Enrollment began in September 2006 and ended in May 2012. All subjects received the study intervention in the Cardiac ICUs at Boston Children's Hospital (Boston, MA) and C.S. Mott Children's Hospital (Ann Arbor, MI).

Participants gave consent prior to cardiopulmonary bypass (CPB) surgery, randomization occurred perioperatively and initiation of the protocol occurred postoperatively. 9 subjects were removed from the study between the time of randomization and initiation of the protocol (4 for cancellation of CPB , 3 for physician decision, 2 for death).

Participant milestones

Measure	Tight Glycemic Control Insulin : 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.	Standard Care Usual Care : Participants receive standard Cardiac ICU care without tight blood glucose control.
Overall Study STARTED	496	493
Overall Study COMPLETED	490	490
Overall Study NOT COMPLETED	6	3

Reasons for withdrawal

Measure	Tight Glycemic Control Insulin : 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.	Standard Care Usual Care : Participants receive standard Cardiac ICU care without tight blood glucose control.
Overall Study Physician Decision	2	1
Overall Study Death	1	1
Overall Study Cardiopulmonary bypass canceled	3	1

Baseline Characteristics

SPECS: Safe Pediatric Euglycemia in Cardiac Surgery

Baseline characteristics by cohort

Measure	Tight Glycemic Control n=490 Participants Insulin : 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.	Standard Care n=490 Participants Usual Care : Participants receive standard Cardiac ICU care without tight blood glucose control.	Total n=980 Participants Total of all reporting groups
Age, Categorical <=18 years	490 Participants n=5 Participants	490 Participants n=7 Participants	980 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	4.3 months n=5 Participants	4.9 months n=7 Participants	4.6 months n=5 Participants
Sex: Female, Male Female	241 Participants n=5 Participants	217 Participants n=7 Participants	458 Participants n=5 Participants
Sex: Female, Male Male	249 Participants n=5 Participants	273 Participants n=7 Participants	522 Participants n=5 Participants
Region of Enrollment United States	490 participants n=5 Participants	490 participants n=7 Participants	980 participants n=5 Participants

PRIMARY outcome

Timeframe: Measured during participant's ICU stay, a median duration of 3 days.

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.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=490 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Incidence of Nosocomial Infections in the Cardiac ICU	8.6 infections / 1000 pt days	9.9 infections / 1000 pt days

SECONDARY outcome

Timeframe: Day 2 (day after cardiopulmonary bypass surgery).

Population: This outcome (using indirect calorimetry) was not available at the Michigan site, and not captured in Boston participants A) who had been extubated or were receiving only pressure support ventilation, B) without a properly placed catheter allowing for a true mixed venous sample or C) for whom equipment malfunction precluded an accurate measurement.

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.

Outcome measures

Measure	Tight Glycemic Control n=95 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=96 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Cardiac Index (CI)	2.0 liters/min/m^2 Interval 1.1 to 2.8	1.8 liters/min/m^2 Interval 1.2 to 2.6

SECONDARY outcome

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.

Duration of ICU stay spans from post-operative cardiac ICU admission to cardiac ICU discharge.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=490 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Duration of ICU Stay	3 Days Interval 2.0 to 6.0	3 Days Interval 2.0 to 6.0

SECONDARY outcome

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.

Duration of hospital stay spans from post-operative cardiac ICU admission to hospital discharge.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=490 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Duration of Hospital Stay	8 Days Interval 5.0 to 15.0	7 Days Interval 5.0 to 13.0

SECONDARY outcome

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.

Duration of endotracheal intubation spans from endotracheal tube intubation/initiation of mechanical ventilation to endotracheal tube extubation.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=490 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Duration of Endotracheal Intubation	3 Days Interval 2.0 to 5.0	2 Days Interval 1.0 to 5.0

SECONDARY outcome

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).

Mortality is assessed at hospital discharge and at 30 days.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=489 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Mortality at Hospital Discharge.	11 Participants	11 Participants

SECONDARY outcome

Timeframe: Measured at 30 days.

Population: This outcome was not measured for participants lost to follow-up at 30 days post cardiac surgery.

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.

Outcome measures

Measure	Tight Glycemic Control n=488 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=484 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Mortality at 30 Days.	5 Participants	6 Participants

SECONDARY outcome

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.

Cardiac function is assessed by duration of vasoactive support.

Outcome measures

Measure	Tight Glycemic Control n=490 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=490 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Cardiac Function	2 Days Interval 0.0 to 5.0	2 Days Interval 0.0 to 5.0

SECONDARY outcome

Timeframe: Post-operative day 7.

Population: Participants analyzed include those with adequate access for blood sampling, C-reactive protein (CRP) drawn on post-operative day 7 and successful processing and preparation of samples,

Immune function is assessed by C-reactive protein (CRP) on post-operative day 7.

Outcome measures

Measure	Tight Glycemic Control n=91 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=85 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Immune Function	3.1 mg/dL Interval 1.3 to 5.6	4.3 mg/dL Interval 2.4 to 7.4

SECONDARY outcome

Timeframe: Measured during participant's ICU stay on Day 7.

Population: Thyroid hormones were assayed only if the participant remained in the cardiac ICU and there was central venous or arterial access for blood sampling.

Endocrine function is assessed by total triiodothyronine (T3) on post-operative day 7.

Outcome measures

Measure	Tight Glycemic Control n=90 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=81 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Endocrine Function	84 ng/dL Interval 60.0 to 122.0	75 ng/dL Interval 52.0 to 108.0

SECONDARY outcome

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.

Population: Nutritional intake was tracked during the period of critical illness, as defined by the presence of an arterial catheter.

Nutritional status assessed by percentage of total caloric intake as enteral nutrition during critical illness period.

Outcome measures

Measure	Tight Glycemic Control n=397 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=393 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Nutritional Status	41 Percent of total caloric intake Interval 19.0 to 65.0	38 Percent of total caloric intake Interval 11.0 to 66.0

SECONDARY outcome

Timeframe: Measured at one year of age.

Population: Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing completed at greater than 18 months post eligibility.

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.

Outcome measures

Measure	Tight Glycemic Control n=100 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=101 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Neurodevelopmental Evaluation, Cognitive	100.2 Scores on a scale Standard Deviation 13.3	100.8 Scores on a scale Standard Deviation 15.6

SECONDARY outcome

Timeframe: Measured at one year of age.

Population: Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing was completed at greater than 18 months post eligibility.

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.

Outcome measures

Measure	Tight Glycemic Control n=100 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=101 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Neurodevelopmental Evaluation, Language	94.7 Scores on a scale Standard Deviation 13.0	94.7 Scores on a scale Standard Deviation 13.1

SECONDARY outcome

Timeframe: Measured at one year of age.

Population: Participants were not eligible if: born before 3/1/2008 (1 year before start of testing); age greater than one year at time of surgery; died; lived abroad; parent/guardian declined; severe disability precluded testing; did not show for testing; testing completed at greater than 18 months post eligibility.

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.

Outcome measures

Measure	Tight Glycemic Control n=100 Participants Insulin was infused to target a blood glucose concentration of 80-110 mg/dL. Insulin: 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.	Standard Care n=101 Participants Insulin was infused according to the discretion of the treating clinical team. Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Neurodevelopmental Evaluation, Motor	87.2 Scores on a scale Standard Deviation 15.8	88.9 Scores on a scale Standard Deviation 16.9

Adverse Events

Insulin

Serious events: 16 serious events

Other events: 15 other events

Deaths: 0 deaths

Usual Care

Serious events: 5 serious events

Other events: 19 other events

Deaths: 0 deaths

Serious adverse events

Measure	Insulin n=490 participants at risk Insulin: 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.	Usual Care n=490 participants at risk Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Endocrine disorders Severe hypoglycemia (BG < 40 mg/dL)	3.3% 16/490 • Entire course of protocol, up to 28 days	1.0% 5/490 • Entire course of protocol, up to 28 days

Other adverse events

Measure	Insulin n=490 participants at risk Insulin: 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.	Usual Care n=490 participants at risk Usual Care: Participants receive standard Cardiac ICU care without tight blood glucose control.
Endocrine disorders Hypokalemia (K < 2.0 mmol/L)	3.1% 15/490 • Entire course of protocol, up to 28 days	3.9% 19/490 • Entire course of protocol, up to 28 days

Additional Information

Dr. Michael Agus

Boston Children's Hospital

Phone: 617-355-5849

Email: michael.agus@childrens.harvard.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place