Intensive Glycemic Control for Congestive Heart Failure Exacerbation

• Sponsor: Kathleen Dungan (Other)
• Overall Status: Completed
• CT.gov ID: NCT00812253
• Collaborator: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (NIH)
• Enrollment: 74
• Location: 1
• Arms: 2
• Duration (Months): 63.9
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

Patients with heart failure often have high blood sugar (glucose).

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

Detailed Description

Patients with heart failure often have high blood sugar. High glucose contributes to severe hospital complications and even death. Studies suggest that heart failure patients who have high glucose or diabetes do not live as long as patients with normal glucose. In this study, we will determine whether normalizing blood sugars using intravenous insulin short-term will improve outcomes in patients hospitalized for congestive heart failure. We enrolled patients with severe heart failure and randomly assigned them into 2 groups. We used intravenous (given through the vein) insulin to lower blood sugar levels in group 1, and insulin injections in group 2. We determined whether intravenous insulin improved hospital length of stay, rates of readmission, inflammatory markers, and cardiovascular tests that predict mortality in patients with heart failure.

Study Design

• Study Type: Interventional
• Actual Enrollment: 74 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Intensive Glycemic Control for Congestive Heart Failure Exacerbation
• Study Start Date: Jan 1, 2009
• Actual Primary Completion Date: Sep 1, 2013
• Actual Study Completion Date: May 1, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Intravenous Insulin	Drug: Intravenous insulin; Half of subjects will receive insulin through the intravenous route while the other half will receive 4 injections per day.
Active Comparator: Subcutaneous Insulin Basal bolus insulin (4 injections per day)	Drug: Subcutaneous insulin; Half of subjects will receive insulin through the intravenous route while the other half will receive 4 injections per day.

Outcome Measures

Primary Outcome Measures

1. Hospital Length of Stay [Days]

   Duration of hospitalization in days

Secondary Outcome Measures

1. Hospital Readmission [30 days]

   All-cause hospital readmission at 30 days after discharge

2. Heart Rate Variability [72 hours]

   High frequency (HF) Heart rate variability (HRV). HRV was assessed with a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration and impedance cardiography was performed using a standard tetrapolar arrangement. Measures were performed at baseline and each morning (0800-1000 hour) during and following the intervention for 7 minutes each. Software (Mindware, Gahanna, OH) was used to derive HF HRV. The middle five minutes of the recordings were scored minute by minute and the first suitable1 minute period was used for calculation. Five minute epochs were not feasible due to an unexpectedly high frequency of ectopy. One minute intervals allow calculation of HF (parasympathetic tone) but not low frequency (combination of sympathetic and parasympathetic tone).

3. Change in Quality of Life [30 day]

   Change in Quality of Life questionnaire measured from baseline (enrollment) to 30 days following discharge. The questionnaire is a self-administered disease-specific questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on health related quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL),

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

   Brain natriuretic peptide (BNP) was measured at day 3

5. Cardiac Output [72 hours]

   Cardiac output measured using impedance cardiography at 72 hours.

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 OSU Ross Heart Hospital 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: NCT00812253
• Other Study ID Numbers: 2007H0197; 1K23DK080891-01A1
• First Posted: Dec 22, 2008
• Last Update Posted: Jan 2, 2018
• Last Verified: Dec 1, 2017

• Keywords provided by Kathleen Dungan, Assistant Professor, Ohio State University: Heart failure; Hyperglycemia; Hospital; Diabetes Mellitus
• Additional relevant MeSH terms: Heart Failure; Diabetes Mellitus; Insulin; Insulin, Globin Zinc

Study Results

Participant Flow

Arm/Group Title	Intravenous Insulin (IV)	Subcutaneous Insulin
Arm/Group Description	Intravenous insulin: In patients assigned to intravenous (IV) insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Period Title: Overall Study
STARTED	32	42
COMPLETED	26	39
NOT COMPLETED	6	3

Baseline Characteristics

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin	Total
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.	Total of all reporting groups
Overall Participants	26	39	65
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	61 (10)	63 (12)	62 (11)
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%
Preserved ejection fraction (participants) [Number]
Preserved Ejection Fraction	6 23.1%	11 28.2%	17 26.2%
Reduced Ejection Fraction	20 76.9%	28 71.8%	48 73.8%
HbA1c (Percentage of hemoglobin) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Percentage of hemoglobin]	8.4 (2.0)	7.7 (1.4)	8.0 (1.7)

Outcome Measures

1. Primary Outcome

Title	Hospital Length of Stay
Description	Duration of hospitalization in days
Time Frame	Days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	26	39
Median (Inter-Quartile Range) [days]	7	8

2. Secondary Outcome

Title	Hospital Readmission
Description	All-cause hospital readmission at 30 days after discharge
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	26	39
Readmitted	7 26.9%	15 38.5%
Not readmitted	19 73.1%	24 61.5%

3. Secondary Outcome

Title	Heart Rate Variability
Description	High frequency (HF) Heart rate variability (HRV). HRV was assessed with a Bionex system (Mindware, Gahanna, OH). The electrocardiogram was performed in the standard lead II configuration and impedance cardiography was performed using a standard tetrapolar arrangement. Measures were performed at baseline and each morning (0800-1000 hour) during and following the intervention for 7 minutes each. Software (Mindware, Gahanna, OH) was used to derive HF HRV. The middle five minutes of the recordings were scored minute by minute and the first suitable1 minute period was used for calculation. Five minute epochs were not feasible due to an unexpectedly high frequency of ectopy. One minute intervals allow calculation of HF (parasympathetic tone) but not low frequency (combination of sympathetic and parasympathetic tone).
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Subjects with medical devices, conditions that preclude measurement of HRV such as arrhythmias, or technical problems could not be analyzed.

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	12	10
Median (Inter-Quartile Range) [ms^2]	5.1	20.7

4. Secondary Outcome

Title	Change in Quality of Life
Description	Change in Quality of Life questionnaire measured from baseline (enrollment) to 30 days following discharge. The questionnaire is a self-administered disease-specific questionnaire for patients with HF, comprising 21 items rated on six-point Likert scales, representing different degrees of impact of HF on health related quality of life, from 0 (none) to 5 (very much). It provides a total score (range 0-105, from best to worst HRQoL),
Time Frame	30 day

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	19	35
Mean (Standard Deviation) [units on a scale]	-22.4 (22.0)	-22.6 (26.3)

5. Secondary Outcome

Title	Brain Natriuretic Peptide (BNP)
Description	Brain natriuretic peptide (BNP) was measured at day 3
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	26	39
Median (Inter-Quartile Range) [pg/ml]	794	356

6. Secondary Outcome

Title	Cardiac Output
Description	Cardiac output measured using impedance cardiography at 72 hours.
Time Frame	72 hours

Outcome Measure Data

Analysis Population Description

Patients without data due to medical devices, conditions that preclude measurement of PEP such as arrhythmias, or technical problems.

Arm/Group Title	Intravenous (IV) Insulin	Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.	Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
Measure Participants	13	11
Mean (Standard Deviation) [liter/min]	10.3 (9.3)	8.6 (3.5)

Adverse Events

Time Frame	72 hours after enrollment
Arm/Group Title	Intravenous (IV) Insulin		Subcutaneous (SQ) Insulin
Arm/Group Description	Intravenous (IV) insulin: In patients assigned to IV insulin, SQ basal insulin was discontinued and IV insulin was started at 21:00 on the day of enrollment. Patients continued to receive subcutaneous prandial insulin. All patients receiving IV insulin were managed using our hospital's universal nursing run guideline, which has a target glucose of 6.1-8.3 mmol/l. Patients were transitioned from the infusion after 48 hours using approximately 70% of the estimated basal insulin infusion requirement with 4 hours of overlap.		Basal bolus insulin (4 injections per day) In subjects who were insulin naïve, the total daily dose of insulin was calculated as 0.4 or 0.5 unit/kg if the enrollment glucose was <11.1 mmol/l or >11.1 mmol/l respectively. In subjects who were not insulin naive, the total insulin dose was calculated as 100% or 120% of the total daily insulin dose at admission in subjects with an enrollment glucose of <11.1 mmol/l or >11.1 mmol/l respectively. Basal and prandial insulin were administered in approximately equal total daily doses with correction dosing and adjustments based upon a published algorithm. The target glucose range was 5.6-8.3 mmol/l.
All Cause Mortality
	Intravenous (IV) Insulin		Subcutaneous (SQ) Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Intravenous (IV) Insulin		Subcutaneous (SQ) Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/26 (0%)		0/39 (0%)
Other (Not Including Serious) Adverse Events
	Intravenous (IV) Insulin		Subcutaneous (SQ) Insulin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/26 (34.6%)		3/39 (7.7%)
Endocrine disorders
Hypoglycemia	9/26 (34.6%)		3/39 (7.7%)

Limitations/Caveats

HRV and impedance data were limited due to medical devices, conditions that preclude measurement of HRV such as arrhythmias, or technical problems (N=2). The remainder of missing data were due to early hospital discharge.

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.