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| ID | Type | Description | Link |
|---|---|---|---|
| 2014-001877-15 | EudraCT Number |
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| Name | Class |
|---|---|
| AstraZeneca | INDUSTRY |
| Isala | OTHER |
| Spaarne Gasthuis | OTHER |
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Purpose of this study is to treat glucocorticoid induced hyperglycemia due to glucocorticoid pulse therapy in a efficacious, safe and convenient way. Patients with acute exacerbation of COPD treated with glucocorticoid pulse therapy and at high risk for glucocorticoid induced hyperglycemia (defined as known type 2 DM or glucose > 10mmol/l at admission) will be randomized to treatment of dapagliflozin or placebo orally, once daily.
Percentage of time within glucose target range (3,9-10 mmol/l) and incidence rate of hypoglycemia will be compared between dapagliflozin group and placebo group.
Rationale: Patients hospitalized for COPD exacerbation treated with high dose glucocorticoids, frequently develop hyperglycaemia. Currently, sliding scale insulin is often used to bridge such episodes. However, sliding scale insulin is patient unfriendly, does not reduce glycaemic excursion nor glycaemic variability. In contrast, pharmacologic inhibition of the sodium glucose transporter-2 (SGLT-2) can be given as an oral agent and is likely to result in better glucose control with lower risk of hypoglycaemia Objective: glucose control and safety (risk of hypoglycaemia). Secondary objectives are patient satisfaction, other safety outcomes and other parameters of glucose control Study design: Double-blind placebo controlled intervention study Study population: Patients hospitalized for an exacerbation of chronic obstructive lung disease who are treated with high dose glucocorticoids.
Intervention: One group receives once daily a 10mg tablet of dapagliflozin and the other group receives once daily a placebo tablet as add on to their prestudy glucose-lowering medication. Both groups will be treated with glucose lowering escape medication if required.
Main study parameters/endpoints: Glucose control is measured as the average time spent within target range in each patient. Safety is measured as the incidence rate of hypoglycaemia during study follow-up.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The burden of participation consists of the extra capillary glucose measurements that will be done 3-4 times daily and wearing a coin size glucose sensor. Furthermore, patients have to fill out a treatment satisfaction questionnaire. There will be no extra site visits for participants.
Dapagliflozin (experimental group) carries a risk of hypoglycaemia, especially for patient who have concomitant therapy with insulin or sulfonylurea derivatives. Patients will be instructed to anticipate, and if required dosing of glucose lowering therapy will be adjusted. Furthermore, dapagliflozin carries an increased risk of urogenital infections, increased haematocrit and LDL cholesterol.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Dapagliflozin + sliding scale insulin. | Experimental | Treatment with dapagliflozin 10mg once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels > 12 mmol/l, subjects will receive escape treatment with sliding scale insulin. |
|
| Placebo + sliding scale insulin | Placebo Comparator | Treatment with placebo once daily orally. Treatment will start as soon as possible after initation of glucocorticoid pulse therapy for acute exacerbation COPD and will end when pulse therapy is finished (expected duration 10-14 days). In case of persistent glucose levels > 12 mmol/l, subjects will receive escape treatment with sliding scale insulin. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Dapagliflozin | Drug | Dapagliflozin 10mg during glucocorticoid therapy for acute exacerbation COPD |
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| Measure | Description | Time Frame |
|---|---|---|
| Glucose control | % time within target range (3.9-10 mmol/l) | 2nd till 7th day of treatment |
| Risk of hypoglycemia | Incidence rate of hypoglycaemic events | Randomisation till end of study (expected duration of 12 days) |
| Measure | Description | Time Frame |
|---|---|---|
| Patient satisfaction | Diabetes treatment satisfaction questionnaire for inpatients | During hospital stay (expected average of 9 days) |
| Clinical outcomes | Duration of hospitalisation, need for treatment escalation, incidence (re-)infections, change in body weight and blood pressure. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Victor Gerdes, MD, PhD | Slotervaart Hospital | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Slotervaart Hospital | Amsterdam | 1066 EC | Netherlands | |||
| OLVG West |
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| Label | URL |
|---|---|
| Related Info | View source |
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| ID | Term |
|---|---|
| D029424 | Pulmonary Disease, Chronic Obstructive |
| D006943 | Hyperglycemia |
| ID | Term |
|---|---|
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D002908 | Chronic Disease |
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| ID | Term |
|---|---|
| C529054 | dapagliflozin |
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| Sliding scale insulin | Drug | Sliding scale insulin with short acting insulin based on current glucose levels |
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| During hospital stay (expected average of 9 days) |
| Safety | incidence rate of asymptomatic hypoglycaemia, incidence adverse events of special interest (genital infections, urinary tract infections, renal impairment, liver injury and breast-, bladder- and prostate cancer), incidence of other adverse events. | Randomisation till end of study (expected duration of 12 days) |
| Amsterdam |
| Netherlands |
| Spaarne Ziekenhuis | Hoofddorp | Netherlands |
| Isala | Zwolle | Netherlands |
| D020969 |
| Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |