Glucose Control During Glucocorticoid Therapy in Acute Exacerbation of Chronic Obstructive Pulmonary Disease (GluCon-COPD)

Randomized, Double-blind, Placebo-controlled Trial on the Effectiveness and Safety of Dapagliflozin for Blood Glucose Control During Glucocorticoid Treatment for Acute Exacerbation COPD

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.

Study Overview

• Status: Completed
• Conditions: Hyperglycemia Steroid-induced
• Intervention / Treatment: Drug: Dapagliflozin; Drug: Sliding scale insulin

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Phase 4

Contacts and Locations

Study Locations

• Netherlands
  • Amsterdam, Netherlands, 1066 EC
    • Slotervaart Hospital
  • Amsterdam, Netherlands
    • OLVG West
  • Hoofddorp, Netherlands
    • Spaarne Ziekenhuis
  • Zwolle, Netherlands
    • Isala

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Informed consent
• Hospitalization due to AECOPD
• Treatment with ≥30mg prednisone daily or equivalent dose of glucocorticoid for AECOPD
• An expected duration of glucocorticoid treatment of 3-14 days at study entry
• Known type 2 diabetes or glucose ≥ 10 mmol/l at admission

Exclusion Criteria:

• High dose glucocorticoid treatment started ≥7 days before study entry
• Need for ICU admission
• Chronic kidney disease stage G3 (glomerular filtration rate <60ml/minute)
• Recurrent genital or urinary tract infection
• Current use of any SGLT-2 inhibiting agent
• Suspected volume depletion
• Congestive heart failure functional classification NYHA class IV/IV or instable heart failure
• Acute stroke within 2 months before inclusion.
• Recent cardiovascular event: acute coronary syndrome, hospitalisation for unstable angina or coronary revascularisation within 2 months before inclusion
• Suspected liver disease, confirmed by AST/ALT > 3x ULN or bilirubin >2.0mg/dl (34.2 μmol/l) or serologically proven infection with hepatitis B or hepatitis C
• Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Dapagliflozin + sliding scale insulin.; 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.	Drug: Dapagliflozin; Dapagliflozin 10mg during glucocorticoid therapy for acute exacerbation COPD; Other Names: Forxiga; Drug: Sliding scale insulin; Sliding scale insulin with short acting insulin based on current glucose levels; Other Names: Supplemental insulin
Placebo Comparator: Placebo + sliding scale insulin; 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.	Drug: Sliding scale insulin; Sliding scale insulin with short acting insulin based on current glucose levels; Other Names: Supplemental insulin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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)

Secondary Outcome Measures

Outcome Measure	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.	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)

Collaborators and Investigators

• Sponsor: Slotervaart Hospital
• Collaborators: AstraZeneca; Spaarne Gasthuis; Isala
• Investigators: Principal Investigator: Victor Gerdes, MD, PhD, Slotervaart Hospital

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): February 1, 2015
• Primary Completion (Actual): March 1, 2016
• Study Completion (Actual): May 1, 2017

Study Registration Dates

• First Submitted: September 22, 2014
• First Submitted That Met QC Criteria: September 26, 2014
• First Posted (Estimate): October 1, 2014

Study Record Updates

• Last Update Posted (Actual): May 22, 2018
• Last Update Submitted That Met QC Criteria: May 19, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: COPD; hyperglycemia; acute exacerbation; glucocorticoid therapy
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Hyperglycemia; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Sodium-Glucose Transporter 2 Inhibitors; Insulin; Insulin, Globin Zinc; Dapagliflozin
• Other Study ID Numbers: NL49690.048.14; 2014-001877-15 (EudraCT Number)