Efficacy and Safety of a Glargine-based Hospital Discharge Algorithm in Coronary Artery Bypass Graft (CABG) Patients

Study Overview
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Brief Summary
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Most coronary artery bypass graft surgery (CABG) patients develop high blood sugar while they are in the hospital. No studies have shown what the best insulin regimen is for CABG patients with type 2 diabetes is after going home from the hospital. Patients with high blood sugar and diabetes after cardiac bypass surgery will be followed for 3 months to look at how well their treatment(s) for diabetes work after discharge. Patients with diabetes will be discharged on oral antidiabetic drugs or with insulin glargine injections based on their sugar control. Patients with admission HbA1c < 7% (a laboratory value that shows the average blood sugar level in the body over 3 months) will be discharged on the same diabetes medications that they used before coming to the hospital. Those with an HbA1c between 7% and 9% will be discharged on insulin glargine at 50%-80% of the dose used in the hospital and oral antidiabetic drugs. Those with an HbA1c > 9% will be discharged on glargine at 80-100% of the dose used in the hospital in addition to oral antidiabetic drugs or with insulin glargine and insulin glulisine. The primary outcome will be a change in HbA1c at 4 and 12 weeks after discharge.

Detailed Description
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Hospital discharge represents a critical time for ensuring a safe transition to the outpatient setting and reducing the need for emergency department visits and re-hospitalization. Poor coordination of patient care and education on insulin administration at the time of patient discharge to home may be associated with medical errors that may increase risk of hypoglycemia, hyperglycemia and hospital readmission. No prospective studies have examined the impact of a discharge treatment regimen after cardiac surgery. Therefore, this study aims to determine the efficacy and safety of an HbA1c based treatment algorithm in controlling blood glucose (BG) after discharge. The total duration of the study is 3 months. This study will include diabetic and non-diabetic subjects who participated in the American Diabetes Association (ADA) trial entitled Intensive Insulin Therapy in Patients Undergoing Coronary Artery Bypass Surgery. The ADA study is a two-arm randomized multicenter, open-label controlled trial aimed to determine if intensive insulin control with a BG target of 100-140mg/dl will reduce perioperative complications compared to a conventional BG control with a target of 141-180 mg/dl in hyperglycemic subjects who undergo coronary artery bypass graft surgery (CABG). Treatment recommendations at discharge: Patients with admission HbA1c < 7%: Patients without a history of diabetes not requiring subcutaneous (SC) insulin in the hospital will be discharged on no antidiabetic therapy. Patients without a history of diabetes requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. A patient without a history of diabetes who requires SC insulin is likely a newly diagnosed diabetic. The HbA1c value will be important to confirm the diagnosis. If the HbA1c is >6.5%, he/she will be diagnosed with diabetes. We do not anticipate that a patient without a history of diabetes and with an HbA1c <6.5% will require insulin treatment or oral agents long-term. Those patients will be discharged on no anti diabetic therapy with repeated testing after discharge to rule out diabetes. Patients with a history of diabetes will be discharged on their same outpatient antidiabetic regimen (diet, oral antidiabetic agents and/or insulin). Assure there are no contraindications to oral agents (i.e.Thiazolidinediones (TZDs) and heart failure; metformin and renal failure or heart failure). Patients with Admission HbA1c between 7% and 9%: Treatment naïve patients not on any pharmacologic treatment prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of basal (glargine) insulin at 50% of total daily hospital dose. Patients treated with oral antidiabetic agents or glucagon-like peptide-1 (GLP1) analogs prior to admission will be discharged on pre-admission oral antidiabetic therapy plus a single dose of glargine insulin at 50% of the total daily hospital dose. Patients treated with combination of oral antidiabetic agents and basal insulin (NPH insulin also known as Neutral Protamine Hagedorn insulin, glargine, detemir) prior to admission will be discharged on pre-admission oral antidiabetic therapy plus a single dose of glargine insulin or with basal bolus insulin regimen at 50% of total daily hospital dose. Patients not to be treated with oral agents will be discharged on glargine monotherapy or basal bolus at 100% of inpatient total daily dose. Admission HbA1c ≥ 9% prior to admission: Discharge on basal bolus regimen at same inpatient total daily insulin dose. Basal insulin (glargine) once daily, at the same time of the day. Rapid-acting insulin (glulisine) before meals. Alternative treatment: If no contraindications to oral agents (i.e., Thiazolidinediones (TZDs) and heart failure; metformin and renal failure) restart oral agents in combination to glargine once daily at 80% of total daily hospital dose.

Official Title
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Prospective Study Aim to Determine the Efficacy and Safety of a Glargine-based Hospital Discharge Algorithm in Cardiac Surgery Patients With Perioperative Hyperglycemia

Conditions
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Poor Glycemic Control

Intervention / Treatment
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* Drug: Metformin
* Drug: Glargine insulin
* Drug: Glulisine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males or females between the ages of 18 and 80 years undergoing primary coronary artery bypass graft surgery (CABG). Post surgical hyperglycemia (Blood glucose >140 mg/dl) Patients with and without a history of type 2 diabetes Exclusion Criteria: Patients with severely impaired renal function (serum creatinine ≥3.0 mg/dl or a glomerular filtration rate < 30 ml/min) or clinically significant hepatic failure. Subjects with acute hyperglycemic crises such as diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic states. Moribund patients and those at imminent risk of death (brain death or cardiac standstill). Patients or next-to-kin with mental conditions rendering the subject or family member unable to understand the nature, scope, and possible consequences of the study. Female subjects who are pregnant or breast-feeding at time of enrollment into the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control HbA1c < 7%<br>Subjects not requiring coronary artery bypass graft surgery (CABG), with no history of diabetes with HbA1c <7% not requiring subcutaneous insulin in the hospital will be discharged on no antidiabetic therapy. | |
| Active Comparator: Diabetic/ Metformin and 50-Glargine HbA1c 7%- 9%<br>Subjects requiring coronary artery bypass graft surgery (CABG) with a history of diabetes with HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of basal (glargine) insulin at 50% of total daily hospital dose. | Drug: Metformin<br>* Metformin is an oral antidiabetic agent used to control high blood glucose levels and is given in divided doses with meals. During treatment initiation and dose titration, the patient's blood glucose levels will be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Patients without a history of diabetes and admission HbA1c < 7% requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. Treatment naïve patients with an HbA1c between 7% and 9% prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of subcutaneous insulin.<br>* Other names: Glucophage;Drug: Glargine insulin<br>* Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c > 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.<br>* Other names: Lantus;|
| Active Comparator: Diabetic/ Metformin and 80-Glargine HbA1c 7%-9%%<br>Subjects requiring coronary artery bypass graft surgery (CABG) with a history of diabetes with HbA1c 7%- 9% will be discharged on oral metformin and a single dose of basal (glargine) insulin at 80% of total daily hospital dose or with basal bolus regimen at same inpatient total daily insulin dose. | Drug: Metformin<br>* Metformin is an oral antidiabetic agent used to control high blood glucose levels and is given in divided doses with meals. During treatment initiation and dose titration, the patient's blood glucose levels will be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Patients without a history of diabetes and admission HbA1c < 7% requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. Treatment naïve patients with an HbA1c between 7% and 9% prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of subcutaneous insulin.<br>* Other names: Glucophage;Drug: Glargine insulin<br>* Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c > 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.<br>* Other names: Lantus;|
| Active Comparator: No diabetes/ Metformin only<br>Subjects requiring coronary artery bypass graft surgery (CABG) with no history of diabetes with HbA1c <7% and persistent hyperglycemia requiring subcutaneous (SC) insulin therapy in the hospital will be discharged on oral metformin. | Drug: Metformin<br>* Metformin is an oral antidiabetic agent used to control high blood glucose levels and is given in divided doses with meals. During treatment initiation and dose titration, the patient's blood glucose levels will be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Patients without a history of diabetes and admission HbA1c < 7% requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. Treatment naïve patients with an HbA1c between 7% and 9% prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of subcutaneous insulin.<br>* Other names: Glucophage;|
| Active Comparator: Diabetic/antidiabetic regimen<br>Subjects requiring coronary artery bypass graft surgery (CABG) with a history of diabetes with HbA1c <7% will be discharged on their same outpatient antidiabetic regimen. Subjects will receive one of the three treatment options based on their blood glucose levels: Metformin alone, both metformin and glargine insulin or glargine alone. | Drug: Metformin<br>* Metformin is an oral antidiabetic agent used to control high blood glucose levels and is given in divided doses with meals. During treatment initiation and dose titration, the patient's blood glucose levels will be used to determine the therapeutic response to metformin and identify the minimum effective dose for the patient. Patients without a history of diabetes and admission HbA1c < 7% requiring SC insulin therapy in the hospital will be discharged on metformin monotherapy. Treatment naïve patients with an HbA1c between 7% and 9% prior to admission will be discharged on metformin monotherapy or a combination of metformin and a single dose of subcutaneous insulin.<br>* Other names: Glucophage;Drug: Glargine insulin<br>* Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c > 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.<br>* Other names: Lantus;|
| Active Comparator: No diabetes/ Insulin only<br>Subjects requiring coronary artery bypass graft surgery (CABG) with no history of diabetes with HbA1c <7% and persistent hyperglycemia will be given subcutaneous (SC) insulin therapy in the hospital. | Drug: Glargine insulin<br>* Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c > 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.<br>* Other names: Lantus;|
| Active Comparator: Diabetes/Insulin only<br>Subjects requiring coronary artery bypass graft surgery (CABG) with an admission HbA1c >9% and persistent hyperglycemia will be given basal insulin (glargine) once daily, at the same time of the day and rapid-acting insulin (glulisine) before meals. | Drug: Glargine insulin<br>* Glargine is a recombinant human insulin analog that exhibits a constant glucose-lowering profile over 24 hours and permits once-daily dosing. It is administered subcutaneously once a day at the same time every day. Patients with an HbA1c between 7% and 9% requiring subcutaneous insulin therapy in the hospital will be discharged on oral metformin and a single dose of glargine insulin at 50% of total daily hospital dose. Patients with an HbA1c > 9% will be discharged on oral metformin and a single dose of glargine insulin at 80% of total daily hospital dose.<br>* Other names: Lantus;Drug: Glulisine<br>* Glulisine is an injectable, recombinant insulin analog. The total daily dose varies between 0.5 to 1 unit/kg/day depending on the levels of blood glucose. Glulisine will be given within 15 minutes before a meal or within 20 minutes after starting a meal.<br>* Other names: Apidra;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy, Measured by a Change in HbA1c Levels | Change in the level of HbA1c in a one month period after discharge from the hospital. The A1c test result is reported as a percentage. Higher percentages indicate higher blood glucose levels in the previous three months. A normal HbA1c level is below 5.7 percent. | One month after hospital discharge | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Readmitted to the Hospital | The number of participants that were readmitted to the hospital 3 months after initial hospital discharge | 3 months after discharge | 
| The Number of Participants Experiencing a Hypoglycemic Event | The number of participants that experienced hypoglycemia, defined as blood glucose levels ≤70 mg/dl. | 3 months after discharge | 
| The Number of Participants Experiencing a Severe Hypoglycemic Event | The number of participants that experienced severe hypoglycemia, defined as blood glucose levels ≤ 40 mg/dl. | 3 months after discharge | 
| Number of Participants Experiencing a Hyperglycemic Event | The number of participants that experienced hyperglycemia, defined as blood glucose levels ≥ 140 mg/dl. | 3 months after discharge | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Coronary Artery Bypass Graft surgery