Glycemic Targets During CPB in Elderly Diabetes

Effects of Two gLycemic targEts During Cardiopulmonary bypAss on Clinical Outcomes in Diabetic Elderly Patients Undergoing caRdiac Surgery (LEADER): A Randomized Controlled Trial

The goal of this clinical trial is to compare the effects of tight versus liberal glycemic management strategies on patient outcomes during cardiopulmonary bypass in elderly diabetic patients undergoing cardiac surgery. The main questions it aims to answer are:

• Which method of glycemic management could reduce the occurrence of postoperative major outcomes and other complications in patients?
• During cardiopulmonary bypass, are the range of glycemic
• fluctuations, the duration of hyperglycemia, and the incidence of hypoglycemia associated with the risk of postoperative complications?

Participants will:

• Blood sugar control and invasive glycemic monitoring during intraoperative cardiopulmonary bypass
• Record whether major endpoint events and secondary endpoint events occurred and the number of times
• Record intraoperative and postoperative physiological and biochemical indicators

Study Overview

• Status: Not yet recruiting
• Conditions: Glycemic Management During CPB in Elderly Diabetic Cardiac Surgery
• Intervention / Treatment: Other: Tight Glycemic Management Protocol; Drug: Short-acting Insulin; Other: Liberal Glycemic Management Protocol

• Study Type: Interventional
• Enrollment (Estimated): 3000
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Feilong Hei, MD; Phone Number: +86 13311573372; Email: heifeilong@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Age: age ≥ 60 years old.
2. Diagnosis: Preoperative diagnosis of Type 2 Diabetes Mellitus (T2DM), with a history of regular glucose-lowering therapy for at least 3 months prior to surgery.
3. Procedure: Undergoing elective cardiac surgery requiring cardiopulmonary bypass (CPB).
4. Complexity: Undergoing combined cardiac procedures (e.g., any combination of two or more of the following: CABG, valvular surgery, congenital heart repair, cardiomyopathy correction, or great vessel surgery).
5. Informed Consent: Willing and able to provide written informed consent.

Exclusion Criteria:

1. Surgical Factors: Emergency surgery, redo sternotomy, heart transplantation, or left ventricular assist device (LVAD) implantation.
2. Organ Dysfunction: Severe hepatic insufficiency (Child-Pugh Class C) or pre-existing dependence on renal replacement therapy (RRT).
3. Neurological Status: History of severe disabling stroke (mRS > 3) or dementia that prevents meaningful neurological assessment.
4. Acute Metabolic Complications: Occurrence of diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS) within 1 month prior to surgery, or a history of recurrent severe hypoglycemia within the past year.
5. Glycemic Baseline: Preoperative HbA1c > 10%.
6. Pregnancy/Lactation: Women who are currently pregnant or breastfeeding.
7. Life Expectancy: Terminal illness with an expected survival of less than 3 months.
8. Communication Barriers: Inability to effectively communicate or provide informed consent due to mental, legal, or other disabilities.
9. Co-enrollment: Concurrent participation in another perioperative interventional clinical trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Tight Glycemic Control Group; Glycemia is controlled at 5-8 mmol/L during CPB	Other: Tight Glycemic Management Protocol; Participants receive IV insulin infusion during cardiopulmonary bypass (CPB) to maintain blood glucose between 5-8 mmol/L. Monitoring is performed every 30 minutes. Hypoglycemia (<70 mg/dL) is treated with glucose and insulin suspension. Severe hypoglycemia (<54 mg/dL) triggers immediate reporting to the Safety Monitoring Committee. All interventions follow a standardized algorithm.; Drug: Short-acting Insulin; 通过微量泵给予静脉胰岛素输注，以维持血糖在指定的目标范围内（11-14 mmol/L 或 5-8 mmol/L）。包括标准低血糖安全方案：当血糖 <70 mg/dL 时给予救援葡萄糖，当血糖 <54 mg/dL 时强制报告不良事件。
Experimental: Liberal Glycemic Control Group; Glycemia is controlled at 11-14 mmol/L during CPB	Drug: Short-acting Insulin; 通过微量泵给予静脉胰岛素输注，以维持血糖在指定的目标范围内（11-14 mmol/L 或 5-8 mmol/L）。包括标准低血糖安全方案：当血糖 <70 mg/dL 时给予救援葡萄糖，当血糖 <54 mg/dL 时强制报告不良事件。; Other: Liberal Glycemic Management Protocol; Participants receive IV insulin infusion during cardiopulmonary bypass (CPB) to maintain blood glucose between 11-14 mmol/L. Monitoring is performed every 30 minutes. Safety protocols for hypoglycemia (rescue glucose for <70 mg/dL and reporting for <54 mg/dL) are identical to the active control group. All interventions follow a standardized algorithm.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite of major adverse cardio-cerebro-renal and vascular events (MACCE+)	A composite of major complications defined as: All-cause mortality: Death from any cause. CSA-AKI: KDIGO Stage 1-3. Perioperative MI: According to the 4th Universal Definition of MI (2018). For CABG-related MI (within 48h), defined as cTn >10x 99th percentile URL with new pathological Q-waves/LBBB, new graft/native coronary occlusion, or new loss of viable myocardium/WMA. For non-CABG, cTn >99th percentile URL with ischemic symptoms, new ST-T changes/LBBB, or pathological Q-waves. Stroke: New intracranial hemorrhage or infarction confirmed by CT, with or without neurological deficits (e.g., motor/sensory impairment, aphasia). Hepatic Dysfunction: Grade ≥3 according to CTCAE v6.0.	From the day of surgery up to 30 days postoperatively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Postoperative 30-day All-cause Mortality	Incidence of all-cause mortality, defined as any death occurring from the day of surgery until the 30th postoperative day, regardless of the underlying cause or mechanism of death.	From the day of surgery up to 30 days postoperatively
Perioperative Renal Dysfunction (CSA-AKI)	Incidence of Cardiac Surgery-Associated Acute Kidney Injury (CSA-AKI) defined according to the Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guideline criteria. The severity of AKI is graded on a scale from Stage 1 to Stage 3, where: Stage 1 is the minimum severity. Stage 3 is the maximum severity. Higher stages indicate a worse clinical outcome (more severe kidney injury). The occurrence is confirmed if a patient meets the criteria for any KDIGO stage within the 30-day postoperative period.	From the day of surgery up to 30 days postoperatively
Perioperative Myocardial Injury and Infarction (PMI)	Defined by the 4th Universal Definition of MI (2018): cTn elevation >99th percentile URL with ≥1 of: ① ischemic symptoms; ② new ST-T changes or LBBB; ③ pathological Q waves; ④ imaging evidence of new loss of viable myocardium or new regional wall motion abnormality (RWMA); ⑤ coronary thrombus via angiography/autopsy. For CABG-related MI (within 48h): In patients with normal baseline, cTn >10x 99th percentile URL plus ≥1 of: ① new pathological Q waves or LBBB; ② documented new graft or native coronary artery occlusion; ③ imaging evidence of new loss of viable myocardium or new RWMA.	From the day of surgery up to 30 days postoperatively
Postoperative Stroke	Defined as a new-onset intracranial cerebral infarction or hemorrhage diagnosed by non-contrast head CT scan. This includes cases with or without associated neurological symptoms and signs, such as motor/sensory deficits, facial palsy, altered consciousness, aphasia, or difficulty in language comprehension.	From the day of surgery up to 30 days postoperatively
Perioperative Hepatic Dysfunction	Incidence of perioperative hepatic dysfunction defined according to the Common Terminology Criteria for Adverse Events (CTCAE) version 6.0. Liver impairment is graded on a scale from Grade 1 to Grade 5, where: Grade 1 represents mild symptoms or asymptomatic conditions (minimum). Grade 5 represents death related to the adverse event (maximum). Higher grades indicate a worse clinical outcome (more severe hepatic dysfunction). Hepatic dysfunction is confirmed when the severity reaches Grade 3 or higher within the 30-day postoperative period.	From the day of surgery up to 30 days postoperatively
New-onset Symptomatic Respiratory Failure	Defined as postoperative mechanical ventilation duration >48 hours, or the necessity for re-intubation or tracheostomy for airway control due to respiratory function decline or suppression where spontaneous breathing is insufficient to maintain normal oxygen saturation.	From the day of surgery up to 30 days postoperatively
Deep Sternal Wound Infection or Mediastinitis	Defined per the US Centers for Disease Control and Prevention (CDC) criteria for deep incisional Surgical Site Infection (SSI). The infection must involve fascial or muscle layers and/or lead to unplanned readmission or reoperation due to deep-seated infection.	From the day of surgery up to 30 days postoperatively
New-onset Mechanical Circulatory Support	Defined as the postoperative implantation of mechanical circulatory support devices, including Intra-aortic Balloon Pump (IABP), Extracorporeal Membrane Oxygenation (ECMO), or Impella. This applies to patients requiring device insertion to maintain hemodynamic stability due to acute decline in cardiac function or circulatory autoregulation.	From the day of surgery up to 30 days postoperatively
New-onset Symptomatic Atrial Fibrillation	Defined as the first occurrence of AF rhythm (lasting ≥30 seconds) confirmed by ECG or continuous monitoring during or within 30 days post-surgery in patients with no prior history of AF. The episode must be accompanied by clinical symptoms such as palpitations, chest tightness, dyspnea, dizziness, or hypotension.	From the day of surgery up to 30 days postoperatively
New-onset In-hospital Infection	Defined as a new infection occurring ≥48 hours after admission or surgery in patients with no prior evidence of infection. Diagnosis requires at least one of: ① positive microbiological culture or radiographic evidence; ② clinical symptoms (fever, leukocytosis, local signs); ③ clinical diagnosis necessitating anti-infective therapy. Includes pneumonia, urinary tract, bloodstream, and surgical site infections.	From the day of surgery up to 30 days postoperatively
Duration of Postoperative Mechanical Ventilation	The time interval measured from the end of the operation to successful extubation (defined as the first instance of autonomous breathing without ventilator support for at least 24 hours). Unit of Measure: Days	From the day of surgery up to 30 days postoperatively (or until ICU discharge)
Length of Stay in the Intensive Care Unit (ICU)	The time interval between the end of the operation and discharge from the ICU.	From the day of surgery up to 30 days postoperatively
Postoperative Hospital Length of Stay	The number of days between the index operation and discharge from the hospital.	From the day of surgery up to 30 days postoperatively
Total Hospitalization Cost	Defined as the total medical expenditure incurred during the entire hospitalization period until discharge	From the day of surgery up to 30 days postoperatively
Intraoperative Glycemic Variability during CPB	The primary metric for glycemic variability is the Coefficient of Variation (CV). Other supporting metrics, including Standard Deviation (SD) and Variability Independent of the Mean (VIM), will also be calculated to provide a comprehensive assessment of glucose fluctuations. Unit of Measure: Percentage (Coefficient of Variation)	From initiation to termination of cardiopulmonary bypass
Time-Weighted Average (TWA) Glucose during CPB	The time-weighted average of blood glucose concentrations to reflect the overall glucose exposure during the procedure. Unit of Measure: mmol/L	From initiation to termination of cardiopulmonary bypass
Duration of Intraoperative Hyperglycemia	Total cumulative time during which the patient's blood glucose levels are measured above 14.0 mmol/L. Unit of Measure: Minutes	From initiation to termination of cardiopulmonary bypass
Incidence of Intraoperative Hypoglycemia	The proportion of participants who experience at least one blood glucose level measurement below 3.9 mmol/L (Yes/No incidence). Unit of Measure: Percentage of participants	From initiation to termination of cardiopulmonary bypass

Collaborators and Investigators

• Sponsor: Beijing Anzhen Hospital
• Collaborators: Beijing Luhe Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: March 11, 2026
• First Submitted That Met QC Criteria: March 16, 2026
• First Posted (Actual): March 20, 2026

Study Record Updates

• Last Update Posted (Actual): March 20, 2026
• Last Update Submitted That Met QC Criteria: March 16, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: clinical outcome; cardiac bypass surgery; different glycemic target during CPB; elderly diabetes
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptide Hormones; Peptides; Amino Acids, Peptides, and Proteins; Insulins; Pancreatic Hormones; Insulin, Short-Acting
• Other Study ID Numbers: TBD123456789

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No