Decade: Ancillary Effects of Dexmedetomidine Sedation After Cardiac Surgery

• Sponsor: The Cleveland Clinic (Other)
• Overall Status: Completed
• CT.gov ID: NCT02004613
• Collaborator: Hospira, now a wholly owned subsidiary of Pfizer (Industry)
• Enrollment: 798
• Location: 1
• Arms: 2
• Actual Duration (Months): 90.6
• Patients Per Site Per Month: 8.8

Study Details

Study Description

Brief Summary

Ancillary Effects of Dexmedetomidine Sedation After Cardiac Surgery

Condition or Disease	Intervention/Treatment	Phase
Heart Disease	Drug: Dexmedetomidine; Drug: Placebo	Phase 4

Detailed Description

The investigator goal is to evaluate the effects of intraoperative and postoperative dexmedetomidine sedation (versus placebo after cardiac surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 798 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Ancillary Effects of Dexmedetomidine Sedation After Cardiac Surgery
• Actual Study Start Date: Jun 1, 2013
• Actual Primary Completion Date: Dec 1, 2018
• Actual Study Completion Date: Dec 18, 2020

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Dexmedetomidine Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively.	Drug: Dexmedetomidine; Dexmedetomidine
Placebo Comparator: Placebo normal saline administration matching dexmedetomidine rate of infusion.	Drug: Placebo; Normal saline administration matching dexmedetomidine rate of infusion; Other Names: Saline

Outcome Measures

Primary Outcome Measures

1. Number of Patients With Atrial Arrhythmia [From the end of surgery to postoperative day 5]

   The occurrence of postoperative atrial arrhythmias

2. Number of Patients With Delirium [From the end of surgery to postoperative day 5]

   The occurrence of postoperative delirium

Secondary Outcome Measures

1. Number of Patients With Acute Kidney Injury [From the end of surgery to postoperative day 5]

   Acute kidney injury is defined according to Acute Kidney Injury Network (AKIN) classifications. No risk means no risk of acute kidney injury, while a higher stage means worse kidney function.

2. Number of Patients With Incisional Pain [90 days after surgery]

   Patients were evaluated at 90 days by modified Brief Pain Inventory.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

1. 18-85 years old;

2. Scheduled for cardiac surgery with bypass (CABG, valve, or combined);

3. Able to provide a written informed consent;

4. Hemodynamically stable (heart rate>= 55).

Exclusion Criteria:

1. Sick sinus syndrome or Wolff-Parkinson-White syndrome

2. Atrio-ventricular block

3. Hypersensitivity or known allergy to dexmedetomidine

4. Hepatic disease, e.g. twice the normal level of liver enzymes

5. Atrial fibrillation within 1 preoperative month;

6. Permanent pacemaker;

7. Use of amiodarone or dexmedetomidine within the last 30 days;

8. Patients with an ejection fraction under 30% or who had severe heart failure

9. Myocardial infarction in the previ¬ous 7 days;

10. Body mass index =< 40 (BMI= mass (kg) / height (m)2);

11. Those taking clonidine within last 48 hours.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cleveland Clinic Main	Cleveland	Ohio	United States	44195

Sponsors and Collaborators

• The Cleveland Clinic
• Hospira, now a wholly owned subsidiary of Pfizer

Investigators

• Principal Investigator: Alparslan Turan, MD, Staff member

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jan 12, 2016

More Information

Publications

None provided.

• Responsible Party: Alparslan Turan, Staff, The Cleveland Clinic
• ClinicalTrials.gov Identifier: NCT02004613
• Other Study ID Numbers: 12-1379
• First Posted: Dec 9, 2013
• Last Update Posted: Apr 6, 2021
• Last Verified: Mar 1, 2021

• Additional relevant MeSH terms: Heart Diseases; Dexmedetomidine

Study Results

Participant Flow

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
Period Title: Overall Study
STARTED	400	398
COMPLETED	398	396
NOT COMPLETED	2	2

Baseline Characteristics

Arm/Group Title	Dexmedetomidine	Placebo	Total
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion	Total of all reporting groups
Overall Participants	398	396	794
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63 (11)	62 (12)	63 (12)
Sex: Female, Male (Count of Participants)
Female	132 33.2%	111 28%	243 30.6%
Male	264 66.3%	283 71.5%	547 68.9%
Race/Ethnicity, Customized (Count of Participants)
white	365 91.7%	363 91.7%	728 91.7%
not white	30 7.5%	31 7.8%	61 7.7%
Region of Enrollment (participants) [Number]
United States	398 100%	396 100%	794 100%
Modified Brief Pain Inventory (Count of Participants)
Overall Severity (any)	95 23.9%	89 22.5%	184 23.2%
Pain interference (any)	85 21.4%	83 21%	168 21.2%

Outcome Measures

1. Primary Outcome

Title	Number of Patients With Atrial Arrhythmia
Description	The occurrence of postoperative atrial arrhythmias
Time Frame	From the end of surgery to postoperative day 5

Outcome Measure Data

Analysis Population Description

2 patients had no Atrial Arrhythmia data.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
Measure Participants	397	395
Count of Participants [Participants]	121 30.4%	134 33.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmedetomidine, Placebo
	Comments	Hypothesis: dexmedetomidine would reduce the incidence of postoperative atrial arrhythmias.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.34
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.91
	Confidence Interval	(2-Sided) 97.8%; 0.72 to 1.15
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Number of Patients With Delirium
Description	The occurrence of postoperative delirium
Time Frame	From the end of surgery to postoperative day 5

Outcome Measure Data

Analysis Population Description

Delirium data is not available in 18 patients.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
Measure Participants	389	387
Count of Participants [Participants]	67 16.8%	46 11.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmedetomidine, Placebo
	Comments	hypothesis: Dexmedetomidine may reduce the incidence of postoperative delirium.
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.48
	Confidence Interval	(2-Sided) 97.8%; 0.99 to 2.23
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	Number of Patients With Acute Kidney Injury
Description	Acute kidney injury is defined according to Acute Kidney Injury Network (AKIN) classifications. No risk means no risk of acute kidney injury, while a higher stage means worse kidney function.
Time Frame	From the end of surgery to postoperative day 5

Outcome Measure Data

Analysis Population Description

Acute kidney injury data is not available in 16 patients.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
Measure Participants	389	389
No risk	348 87.4%	359 90.7%
stage1	33 8.3%	29 7.3%
Stage2	4 1%	0 0%
Stage3	4 1%	1 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmedetomidine, Placebo
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.14
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	1.40
	Confidence Interval	(2-Sided) 97.5%; 0.84 to 2.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Patients With Incisional Pain
Description	Patients were evaluated at 90 days by modified Brief Pain Inventory.
Time Frame	90 days after surgery

Outcome Measure Data

Analysis Population Description

Incisional pain at 90 days is not available in 205 patients.

Arm/Group Title	Dexmedetomidine	Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine	normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
Measure Participants	289	300
Count of Participants [Participants]	79 19.8%	93 23.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Dexmedetomidine, Placebo
	Comments
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.29
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Risk Ratio (RR)
	Estimated Value	0.87
	Confidence Interval	(2-Sided) 97.5%; 0.65 to 1.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	5 days
Arm/Group Title	Dexmedetomidine		Placebo
Arm/Group Description	Dexmedetomidine infusion, without a bolus dose, (or a comparable volume of placebo) will be initiated before the surgical incision at a rate of 0.1 mcg/kg/hr at the end of bypass, the dose will be increased to 0.2 mcg/kg/hr. Postoperatively patients will continue to receive the study medication at a rate of 0.4mcg/kg/hr. The study medication infusion will be continued for a total of 24 hours from the initial administration time intra-operatively. Dexmedetomidine: Dexmedetomidine		normal saline administration matching dexmedetomidine rate of infusion. Placebo: Normal saline administration matching dexmedetomidine rate of infusion
All Cause Mortality
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/394 (0.3%)		1/390 (0.3%)
Serious Adverse Events
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	21/394 (5.3%)		8/390 (2.1%)
Blood and lymphatic system disorders
Hemorrhage	4/394 (1%)		3/390 (0.8%)
Cardiac disorders
asystol	1/394 (0.3%)		1/390 (0.3%)
heart failure	1/394 (0.3%)		0/390 (0%)
re-intervention	0/394 (0%)		1/390 (0.3%)
Cardiogenic shock	1/394 (0.3%)		0/390 (0%)
Myocardial infarction	1/394 (0.3%)		0/390 (0%)
Pericardial effusion	1/394 (0.3%)		0/390 (0%)
Infections and infestations
infection	2/394 (0.5%)		0/390 (0%)
Nervous system disorders
seizure	0/394 (0%)		1/390 (0.3%)
stroke	3/394 (0.8%)		1/390 (0.3%)
Transient Ischemic attack	1/394 (0.3%)		0/390 (0%)
Respiratory, thoracic and mediastinal disorders
Atelectasis	2/394 (0.5%)		0/390 (0%)
Hypoxemia	1/394 (0.3%)		0/390 (0%)
Pneumothorax	1/394 (0.3%)		1/390 (0.3%)
Pulmonary embolism	1/394 (0.3%)		0/390 (0%)
Vascular disorders
hypotension	1/394 (0.3%)		0/390 (0%)
Other (Not Including Serious) Adverse Events
	Dexmedetomidine		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	234/394 (59.4%)		154/390 (39.5%)
Blood and lymphatic system disorders
Clinically important hypotension	224/394 (56.9%)		140/390 (35.9%)
Cardiac disorders
Clinically important bradycardia	36/394 (9.1%)		45/390 (11.5%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.