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Poor enrollment
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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:
Question/Hypothesis:
Among three commonly used insulin regimens, which is most effective for managing post-transplant once-daily glucocorticoid-induced hyperglycemia?
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Neutral protamine hagedorn (NPH) insulin | Active Comparator | 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. |
|
| Regular or Aspart insulin | Experimental | 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 | Experimental | 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Neutral protamine hagedorn (NPH) insulin | Drug |
|
| |
| Measure | Description | Time Frame |
|---|---|---|
| Blood glucose - inpatient | 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 | Time (days) from enrollment to described treatment range, an expected average of 7 days |
| Measure | Description | Time Frame |
|---|---|---|
| Blood glucose - inpatient | Mean inpatient capillary blood glucose (mmol/L) from enrollment to discharge from hospital | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days |
| Post prandial blood glucose - inpatient |
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Inclusion Criteria:
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:
Have at least three pre-meal inpatient capillary blood glucose (CBG) readings ≥ 7.8 mmol/L
Be eating meals by mouth
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Breay W Paty, MD, FRCPC | Vancouver General Hospital, University of British Columbia | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Vancouver General Hospital - Jim Pattison Pavilion | Vancouver | British Columbia | V5Z 1M9 | Canada |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 22058376 | Background | Lane JT, Dagogo-Jack S. Approach to the patient with new-onset diabetes after transplant (NODAT). J Clin Endocrinol Metab. 2011 Nov;96(11):3289-97. doi: 10.1210/jc.2011-0657. | |
| 22475764 | Background | Sarno G, Muscogiuri G, De Rosa P. New-onset diabetes after kidney transplantation: prevalence, risk factors, and management. Transplantation. 2012 Jun 27;93(12):1189-95. doi: 10.1097/TP.0b013e31824db97d. |
| Label | URL |
|---|---|
| Multilingual dietary instructions to be distributed to ALL subjects during study from the Canadian Diabetes Association | View source |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| D007333 | Insulin Resistance |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| ID | Term |
|---|---|
| D007328 | Insulin |
| D000068880 | Isophane Insulin, Human |
| D061267 | Insulin Aspart |
| D000069036 | Insulin Glargine |
| ID | Term |
|---|---|
| D011384 | Proinsulin |
| D061385 | Insulins |
| D010187 | Pancreatic Hormones |
| D036361 | Peptide Hormones |
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| Regular human insulin or Insulin Aspart |
| Drug |
|
|
| Insulin glargine | Drug |
|
|
Mean inpatient two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to discharge from hospital |
| Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days |
| Length of inpatient hospital stay | Length of stay in hospital (days) from enrollment to discharge from hospital | Subjects will be followed from enrollment for the remainder of hospital stay (days), an expected average of 21 days |
| Blood glucose | Mean fasting blood glucose (mmol/L) from enrollment to 3 months | Enrollment to 3 months |
| Hemoglobin A1C | Mean hemoglobin A1C (%) from enrollment to 3 months | Enrollment to 3 months |
| Post prandial blood glucose | Mean two-hour post-lunch capillary blood glucose (mmol/L) from enrollment to 3 months | Enrollment to 3 months |
| Hypoglycemic episodes | 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) | Enrollment to 3 months |
| Glycemic treatment failure | 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. | Enrollment to 3 months |
| Cardiovascular events | New cardiovascular events defined as: myocardial infarction, new or worsened congestive heart failure, stroke, and cardiac arrhythmia. | Enrollment to 3 months |
| Post-transplant infections or new antibiotic use | Post-transplant infections or new antibiotic use from enrollment to 3 months. | Enrollment to 3 months |
| Transplant graft failure | Transplant graft failure (as specified by subject's medical transplant physician) from enrollment to 3 months. | Enrollment to 3 months |
| New acute renal failure | 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 | Enrollment to 3 months |
| Mortality | Overall subject mortality from baseline to 3 months. | Enrollment to 3 months |
| 20439241 | Background | Griffith ML, Jagasia M, Jagasia SM. Diabetes mellitus after hematopoietic stem cell transplantation. Endocr Pract. 2010 Jul-Aug;16(4):699-706. doi: 10.4158/EP10027.RA. |
| 22049542 | Background | Lansang MC, Hustak LK. Glucocorticoid-induced diabetes and adrenal suppression: how to detect and manage them. Cleve Clin J Med. 2011 Nov;78(11):748-56. doi: 10.3949/ccjm.78a.10180. |
| 22223765 | Background | Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, Seley JJ, Van den Berghe G; Endocrine Society. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012 Jan;97(1):16-38. doi: 10.1210/jc.2011-2098. |
| D006946 | Hyperinsulinism |
| D006728 |
| Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D007336 | Insulin, Isophane |
| D049528 | Insulin, Long-Acting |
| D061386 | Insulin, Regular, Human |
| D061266 | Insulin, Short-Acting |