Insulin Therapy for Post-transplant Glucocorticoid Induced Hyperglycemia
- Conditions
- Post-Transplant Glucocorticoid Induced Diabetes
- Interventions
- Drug: Regular human insulin or Insulin Aspart
- Registration Number
- NCT01648218
- Lead Sponsor
- Vancouver General Hospital
- Brief Summary
No consensus guidelines exist for management of post-transplant glucocorticoid induced hyperglycemia, but most published reviews recommend insulin as first line therapy. A variety of insulin regimens have been proposed, including mealtime short-acting regular or analog insulin, once daily neutral protamine hagedorn (NPH) insulin, pre-mixed insulin, or basal insulin alone such as glargine or detemir. However, no randomized trial has ever examined different insulin regimens to determine which most effectively controls post-transplant steroid-induced hyperglycemia. Consequently, the proposed study intends to examine three commonly used insulin regimens used for managing post-transplant once-daily glucocorticoid-induced hyperglycemia to determine which is most effective:
* Group 1: Intermediate-acting (NPH) insulin at breakfast
* Group 2: Short-acting insulin (regular or aspart) before meals
* Group 3: Insulin glargine at breakfast
Question/Hypothesis:
Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 5
-
Have undergone bone marrow, liver, lung, or renal transplant.
-
Be using once daily oral glucocorticoid therapy (total daily dose of Prednisone ≥10 mg, Hydrocortisone ≥40 mg, Dexamethasone ≥1.5 mg) administered in the morning and expected to continue for at least 2 weeks.
-
Have pre-existing or newly diagnosed diabetes mellitus established by any of the criteria listed below:
- Fasting plasma glucose ≥7.0 mmol/L (repeated x 1)
- Any plasma glucose ≥11.0 mmol/L
-
Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
-
Be eating meals by mouth
- Heart, Pancreas, Islet cell transplant recipients
- Previous use of Basal-Bolus or Pre-Mixed Insulin regimen
- Diabetes mellitus type I
- NPO (not eating meals by mouth)
- Receiving enteral (tube feeds) or parenteral (TPN) nutrition
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Regular or Aspart insulin Regular human insulin or Insulin Aspart Drug: Regular human insulin or Insulin Aspart Other Names: Humulin R, Novolin R, Novolog, NovoRapid Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before meals; Duration: 2 hours (Aspart) or 6 hours (Regular); for duration subjects are concurrently administered once-daily glucocorticoid. Insulin glargine Insulin glargine Drug: Insulin glargine Other Names: Lantus Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 24 hours; for duration subjects are concurrently administered once-daily glucocorticoid. Neutral protamine hagedorn (NPH) insulin Neutral protamine hagedorn (NPH) insulin Drug: Neutral protamine hagedorn (NPH) insulin Other Names: Humulin N, Novolin N Route: Subcutaneous; Dosage: No fixed dose, varies between subjects; Frequency: daily before breakfast; Duration: 12 hours; for duration subjects are concurrently administered once-daily glucocorticoid.
- Primary Outcome Measures
Name Time Method Blood glucose - inpatient Time (days) from enrollment to described treatment range, an expected average of 7 days Mean time from baseline to achieve at least 80% of pre-meal capillary blood glucose values within 5.0 - 7.8 mmol/L over a 48 hour period during hospitalization
- Secondary Outcome Measures
Name Time Method Blood glucose Enrollment to 3 months Mean fasting blood glucose (mmol/L) from enrollment to 3 months
Blood glucose - inpatient Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital
Length of inpatient hospital stay Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days Length of stay in hospital (days) from enrollment to discharge from hospital
Glycemic treatment failure Enrollment to 3 months Hypoglycemic treatment failure: subject experiences ≥3 hypoglycemic episodes (≤ 4.0 mmol/L) over any 5 day period or a single severe hypoglycemic event (as previously defined), they will be withdrawn from study and managed at discretion of attending physician, or hospital endocrine consult service.
Hyperglycemic treatment failure: Severe hyperglycemia defined as CBG \>20 mmol/L. If subject experiences ≥3 severe hyperglycemic measures over the course of 48 hours they will be withdrawn from the study and managed at discretion of attending physician, or hospital endocrine consult service.Post-transplant infections or new antibiotic use Enrollment to 3 months Post-transplant infections or new antibiotic use from enrollment to 3 months.
New acute renal failure Enrollment to 3 months New acute renal failure is defined according to Acute Kidney Network Guidelines: rapid time course and decreased kidney function according to an absolute Creatinine (Cr) rise greater than 26 μmol/L, greater than 2-fold increase in serum Cr from baseline, or urine output less than 0.5 mL/kg/hr for greater than 6 hours
Post prandial blood glucose - inpatient Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital
Hemoglobin A1C Enrollment to 3 months Mean hemoglobin A1C (%) from enrollment to 3 months
Post prandial blood glucose Enrollment to 3 months Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months
Hypoglycemic episodes Enrollment to 3 months Hypoglycemic episodes defined as:
(1) Mild - any measured CBG 3.0-4.0 mmol/L; (2) Severe - any episode of hypoglycemia with a measured CBG \< 3.0 mmol/L, OR which the subject is not able to recognize and treat without the direct (substantial) intervention of a professional caregiver, nurse or physician (e.g. intravenous dextrose or intramuscular glucagon)Transplant graft failure Enrollment to 3 months Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months.
Cardiovascular events Enrollment to 3 months New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia.
Mortality Enrollment to 3 months Overall subject mortality from baseline to 3 months.
Trial Locations
- Locations (1)
Vancouver General Hospital - Jim Pattison Pavilion
🇨🇦Vancouver, British Columbia, Canada