Glycemic Control and Variability for Congestive Heart Failure Exacerbation

• Sponsor: Kathleen Dungan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00812487
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 75
• Location: 1
• Arms: 2
• Duration (Months): 56
• Patients Per Site Per Month: 1.3

Study Details

Study Description

Brief Summary

High glucose as well as fluctuations (rapid swings) in blood glucose can contribute to severe hospital complications and even death.

Condition or Disease	Intervention/Treatment	Phase
Congestive Heart Failure; Diabetes Mellitus	Drug: Intravenous insulin; Drug: Subcutaneous insulin	Phase 1/Phase 2

Detailed Description

High glucose as well as fluctuations in blood glucose can contribute to severe hospital complications and even death. Studies also suggest that heart failure patients who have high glucose or diabetes do not live as long as patients with normal glucose. Glucose fluctuations have not been well-studied in patients with heart failure. In this study, we will determine whether better control of blood sugar fluctuations in the hospital improve outcomes. We will enroll 80 patients with severe heart failure and divide them into 2 groups. We will use intravenous (given through the vein) insulin to lower blood sugar levels in group 1, and insulin injections (under the skin) in group 2. We will determine whether intravenous insulin improves blood markers of inflammation, changes in vital signs, and other tests that predict mortality in patients with heart failure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 75 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Glycemic Control and Variability for Congestive Heart Failure Exacerbation
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Aug 1, 2012
• Actual Study Completion Date: Sep 1, 2013

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous insulin	Drug: Intravenous insulin; Patients will receive continuous insulin infusion through the vein.
Active Comparator: Subcutaneous Insulin 4 injections of insulin/day	Drug: Subcutaneous insulin; 4 injections of insulin/day

Outcome Measures

Primary Outcome Measures

1. Hospital Length of Stay [participants were followed for the duration of hospital stay, median hospital stay 8 day]

   Duration of hospitalization

2. Hospital Readmission [30 days]

   All-cause hospital readmission within 30 days

Secondary Outcome Measures

1. High Frequency Heart Rate Variability [24 hours]

   High frequency heart rate variability (HF HRV)is a measure of cardiac autonomic tone. Electrocardiographic measures were obtained using a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration. Software (Mindware, Gahanna, OH) was used to derive HF HRV. HF HRV was calculated using power spectral analysis.

2. Pre-ejection Period (PEP) [24 hours]

   Pre-ejection period (PEP) is the time between the onset of electrical depolarization of the ventricle and the opening of the aortic valve, a measure of sympathetic tone. It is obtained noninvasively using cardiac impedance obtained using a Bionex system (Mindware, Gahanna, OH). PEP is measured in milliseconds; lower values reflect higher sympathetic tone.

3. High Sensitivity C-reactive Protein (Hs-CRP) [72 hours]

   High sensitivity C-reactive Protein (hs-CRP) is a measure of inflammation. hsCRP (range 0-15 mg/L) was performed using Immunlite 1000 assay (Siemens; Erlangen, Germany).

4. Brain Natriuretic Peptide (BNP) [72 hours]

   Laboratory analyses were performed by the study institution's Clinical Research Center using standard commercial kits

5. Quality of Life [30 days]

   Quality of Life was measured using the Minnesota Living with Heart Failure Questionnaire, which is a 21 question survey that uses a likert scale of 0-5. Each item asks over the past 4 weeks whether they have had a particular symptom of heart failure and to classify the response as no symptoms (0) to having the symptom very much (5). Responses are summed for a total score (0-105).

6. Glycemic Lability Index (GLI) [24 hours]

   GLI is a measure of glycemic variability. GLI is the sum of the square of the difference between successive glucose measurements divided by the difference in time between measurements

7. Coefficient of Variation (CV) [24 hours]

   CV is a measure of glycemic variability

8. Mean Glucose [24 hours]

   mean sensor glucose

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Age 18 and above

• Admitted (less than 48 hours) to the with worsening heart failure

• Hyperglycemia or diabetes. Hyperglycemia is defined as blood glucose greater than 150 mg/dL on at least 2 occasions separated by at least 4 hours apart, insulin use, or HbA1c >6.5%.

Exclusion Criteria:

• Type 1 diabetes

• Receiving comfort care measures only

• Hospital stay expected to be less than 2 days

• Pregnancy

• Prisoners

• Participation in the study on prior hospitalizations

• Acute myocardial infarction within 3 months

• End stage renal or liver disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Ohio State University	Columbus	Ohio	United States	43210

Sponsors and Collaborators

• Kathleen Dungan
• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Investigators

• Principal Investigator: Kathleen M Dungan, MD, Ohio State University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Kathleen Dungan, Assistant Professor, Ohio State University
• ClinicalTrials.gov Identifier: NCT00812487
• Other Study ID Numbers: 2008H0087; 1R21DK081877-01
• First Posted: Dec 22, 2008
• Last Update Posted: Dec 31, 2013
• Last Verified: Nov 1, 2013

• Keywords provided by Kathleen Dungan, Assistant Professor, Ohio State University: congestive heart failure; diabetes mellitus; hyperglycemia
• Additional relevant MeSH terms: Heart Failure; Diabetes Mellitus; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Recruitment Details	Hospitalized patients with type 2 diabetes and heart failure exacerbation were recruited between 2008-2013 from an academic medical center.
Pre-assignment Detail	Patients were randomized to intravenous or subcutaneous insulin. There were no pre-assignment changes in therapy before randomization. One patient was excluded after consent but prior to randomization due to receipt of corticosteroids which is an exclusion criterion.

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Period Title: Overall Study
STARTED	32	42
COMPLETED	26	39
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin	Total
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day	Total of all reporting groups
Overall Participants	26	39	65
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	18 69.2%	23 59%	41 63.1%
>=65 years	8 30.8%	16 41%	24 36.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61 (9.6)	61.3 (12.4)	61 (9.6)
Sex: Female, Male (Count of Participants)
Female	8 30.8%	13 33.3%	21 32.3%
Male	18 69.2%	26 66.7%	44 67.7%
Region of Enrollment (participants) [Number]
United States	26 100%	39 100%	65 100%

Outcome Measures

1. Secondary Outcome

Title	High Frequency Heart Rate Variability
Description	High frequency heart rate variability (HF HRV)is a measure of cardiac autonomic tone. Electrocardiographic measures were obtained using a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration. Software (Mindware, Gahanna, OH) was used to derive HF HRV. HF HRV was calculated using power spectral analysis.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	15	12
Median (Inter-Quartile Range) [ms^2]	15.5	13.9

2. Secondary Outcome

Title	Pre-ejection Period (PEP)
Description	Pre-ejection period (PEP) is the time between the onset of electrical depolarization of the ventricle and the opening of the aortic valve, a measure of sympathetic tone. It is obtained noninvasively using cardiac impedance obtained using a Bionex system (Mindware, Gahanna, OH). PEP is measured in milliseconds; lower values reflect higher sympathetic tone.
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	14	14
Mean (Standard Deviation) [ms]	120 (24)	117 (20)

3. Secondary Outcome

Title	High Sensitivity C-reactive Protein (Hs-CRP)
Description	High sensitivity C-reactive Protein (hs-CRP) is a measure of inflammation. hsCRP (range 0-15 mg/L) was performed using Immunlite 1000 assay (Siemens; Erlangen, Germany).
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	26	34
Median (Inter-Quartile Range) [mg/dl]	10.5	15.9

4. Secondary Outcome

Title	Brain Natriuretic Peptide (BNP)
Description	Laboratory analyses were performed by the study institution's Clinical Research Center using standard commercial kits
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	22	38
Median (Inter-Quartile Range) [pg/ml]	360	299

5. Secondary Outcome

Title	Quality of Life
Description	Quality of Life was measured using the Minnesota Living with Heart Failure Questionnaire, which is a 21 question survey that uses a likert scale of 0-5. Each item asks over the past 4 weeks whether they have had a particular symptom of heart failure and to classify the response as no symptoms (0) to having the symptom very much (5). Responses are summed for a total score (0-105).
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	20	34
Median (Inter-Quartile Range) [units on a scale]	50.5	45

6. Secondary Outcome

Title	Glycemic Lability Index (GLI)
Description	GLI is a measure of glycemic variability. GLI is the sum of the square of the difference between successive glucose measurements divided by the difference in time between measurements
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	24	34
Median (Inter-Quartile Range) [(mg/dl)^2/hr*day-1]	0.83	0.66

7. Primary Outcome

Title	Hospital Length of Stay
Description	Duration of hospitalization
Time Frame	participants were followed for the duration of hospital stay, median hospital stay 8 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	26	39
Median (Inter-Quartile Range) [days]	7	8

8. Primary Outcome

Title	Hospital Readmission
Description	All-cause hospital readmission within 30 days
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	26	39
Number [participants]	7 26.9%	15 38.5%

9. Secondary Outcome

Title	Coefficient of Variation (CV)
Description	CV is a measure of glycemic variability
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	24	33
Mean (Standard Deviation) [percentage (mean glucose/SD)]	24.5 (10.2)	18.6 (8.5)

10. Secondary Outcome

Title	Mean Glucose
Description	mean sensor glucose
Time Frame	24 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous Insulin	Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.	Patients received basal and bolus insulin, approximately 5 injections of insulin/day
Measure Participants	24	33
Mean (Standard Deviation) [mg/dl]	139 (23)	169 (49)

Adverse Events

Arm/Group Title	Intravenous Insulin		Subcutaneous Insulin
Arm/Group Description	Patients received intravenous insulin according to the hospital nursing run algorithm with a target glucose of 100-150 mg/dl.		Patients received basal and bolus insulin, approximately 5 injections of insulin/day
All Cause Mortality
	Intravenous Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intravenous Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/26 (61.5%)		21/39 (53.8%)
Cardiac disorders
Death	2/26 (7.7%)	2	2/39 (5.1%)	2
Arrhythmia	2/26 (7.7%)	2	4/39 (10.3%)	4
Infections and infestations
Infection	4/26 (15.4%)	4	6/39 (15.4%)	6
Renal and urinary disorders
Acute Renal Failure	6/26 (23.1%)	6	8/39 (20.5%)	8
Respiratory, thoracic and mediastinal disorders
Mechanical ventilation	2/26 (7.7%)	2	1/39 (2.6%)	1
Other (Not Including Serious) Adverse Events
	Intravenous Insulin		Subcutaneous Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	8/26 (30.8%)		4/39 (10.3%)
Metabolism and nutrition disorders
Hypoglycemia	8/26 (30.8%)	25	4/39 (10.3%)	11

Limitations/Caveats

The study was limited by study drop-out. Sensor glucose values were reduced due to sensor failures, and cardiac assessments were limited due to a high number of patients with ectopy, arrhythmia or paced rhythms at baseline precluding analysis.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.