POINT: Effects of Magnesium on Individuals Undergoing Coronary Artery Bypass Graft Surgery

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00041392
• Collaborator: National Heart, Lung, and Blood Institute (NHLBI) (NIH)
• Enrollment: 389
• Location: 1
• Arms: 2
• Duration (Months): 89
• Patients Per Site Per Month: 4.4

Study Details

Study Description

Brief Summary

The purpose of this study is to examine the effects of supplemental magnesium on the neurocognitive function of individuals undergoing coronary artery bypass graft (CABG) surgery.

Condition or Disease	Intervention/Treatment	Phase
Coronary Disease; Heart Diseases; Cardiovascular Diseases; Neurologic Manifestations	Drug: Magnesium; Drug: 0.9% saline	Phase 2

Detailed Description

BACKGROUND:

Approximately 400,000 individuals undergo heart operations each year and cognitive impairment occurs frequently following surgery. An increasing number of these individuals are elderly and are particularly susceptible to cognitive dysfunction following surgery. Cognitive impairment is most notable in the early stages following heart surgery, but it may persist in some individuals. While many people think cognitive impairment is subtle, transient, or subclinical, perioperative decline is associated with 5-year cognitive deterioration and reduced quality of life. Multiple strategies, both clinical and pharmacological, have been proposed to reduce the central nervous system dysfunction associated with heart surgery. However, most strategies have been unsuccessful, met with limited success, or are unrealistic from a cost or risk-benefit ratio for the majority of people. This study will examine the effectiveness of supplemental magnesium at preventing the cognitive decline associated with heart surgery.

DESIGN NARRATIVE:

This study will examine the effect of supplemental magnesium on the neurocognitive function of individuals undergoing CABG surgery. The two hypotheses to be tested include the following: 1) therapeutic levels of magnesium reduce post-operative neurocognitive dysfunction after heart surgery; and 2) therapeutic magnesium levels protect quality of life through reduced cognitive dysfunction after heart surgery. This double-blind study will enroll 400 individuals and randomly assign them to either the treatment group, which will receive 100 mg/kg of magnesium, or to the control group. Anesthesia management will be standardized to minimize any impact that anesthesia may have on neurologic or neuropsychologic outcome. Neurocognitive testing will be conducted prior to surgery, and 6 weeks and 1 year following surgery.

Study Design

• Study Type: Interventional
• Actual Enrollment: 389 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: PeriOperative Interventional Neuroprotection Trial (POINT)
• Study Start Date: Dec 1, 2001
• Actual Primary Completion Date: May 1, 2009
• Actual Study Completion Date: May 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Magnesium 100 mg/kg magnesium	Drug: Magnesium; 100 mg/kg
Placebo Comparator: 0.9 % saline 100 mg/kg 0.9 % saline	Drug: 0.9% saline; Placebo

Outcome Measures

Primary Outcome Measures

1. Cognitive Function [Measured at baseline and 6 weeks]

   To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the cognitive test scores from baseline. We chose a four-factor solution, which represents 4 cognitive domains: verbal memory, abstraction and visuo-spatial orientation (executive function), visual memory and attention and concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 4 preoperative domain scores. The cognitive index score has a mean of zero and standard deviation of 0.5. Thus, any positive score is above the mean, any negative score is below the mean, and a score of 0.5 represents 1 SD above the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. Negative scores indicate decline and positive scores indicate improvement.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 55 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Coronary heart disease

Exclusion Criteria:

• Early dementia

• History of psychiatric illness

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Duke University Medical Center	Durham	North Carolina	United States	27710

Sponsors and Collaborators

• Duke University
• National Heart, Lung, and Blood Institute (NHLBI)

Investigators

• Study Chair: Mark F. Newman, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00041392
• Other Study ID Numbers: Pro00007128; R01HL069081
• First Posted: Jul 9, 2002
• Last Update Posted: Jul 30, 2013
• Last Verified: Apr 1, 2012

• Additional relevant MeSH terms: Neurologic Manifestations; Cardiovascular Diseases; Heart Diseases; Coronary Disease

Study Results

Participant Flow

Recruitment Details	Hospital and preoperative clinic

Arm/Group Title	Magnesium	0.9 % Saline
Arm/Group Description	100 mg/kg magnesium	100 mg/kg 0.9 % saline
Period Title: Overall Study
STARTED	198	191
COMPLETED	198	191
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Magnesium	0.9 % Saline	Total
Arm/Group Description	100 mg/kg magnesium	100 mg/kg 0.9 % saline	Total of all reporting groups
Overall Participants	198	191	389
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	78 39.4%	74 38.7%	152 39.1%
>=65 years	120 60.6%	117 61.3%	237 60.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.6 (8.4)	68.4 (8.0)	68.5 (8.2)
Sex: Female, Male (Count of Participants)
Female	54 27.3%	66 34.6%	120 30.8%
Male	144 72.7%	125 65.4%	269 69.2%
Region of Enrollment (participants) [Number]
United States	198 100%	191 100%	389 100%

Outcome Measures

1. Primary Outcome

Title	Cognitive Function
Description	To characterize cognitive function over time, while minimizing potential redundancy in the cognitive measures, a factor analysis was performed on the cognitive test scores from baseline. We chose a four-factor solution, which represents 4 cognitive domains: verbal memory, abstraction and visuo-spatial orientation (executive function), visual memory and attention and concentration. To quantify overall cognitive function, a baseline cognitive index was first calculated as the mean of the 4 preoperative domain scores. The cognitive index score has a mean of zero and standard deviation of 0.5. Thus, any positive score is above the mean, any negative score is below the mean, and a score of 0.5 represents 1 SD above the mean. A continuous change score was then calculated by subtracting the baseline from the 6-week cognitive index. Negative scores indicate decline and positive scores indicate improvement.
Time Frame	Measured at baseline and 6 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Magnesium	0.9 % Saline
Arm/Group Description	100 mg/kg magnesium	100 mg/kg 0.9 % saline
Measure Participants	198	191
Mean (Standard Deviation) [Continuous cognitive change score]	0.07 (0.28)	0.12 (0.28)

Adverse Events

Arm/Group Title	Magnesium		0.9 % Saline
Arm/Group Description	100 mg/kg magnesium		100 mg/kg 0.9 % saline
All Cause Mortality
	Magnesium		0.9 % Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Magnesium		0.9 % Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/198 (18.7%)		32/191 (16.8%)
Blood and lymphatic system disorders
Bleeding	8/198 (4%)	10	2/191 (1%)	10
Cardiac disorders
Atrial fibrillation	1/198 (0.5%)	2	1/191 (0.5%)	2
Ventricular tachycardia	3/198 (1.5%)	4	1/191 (0.5%)	4
Pacemaker placement	4/198 (2%)	6	2/191 (1%)	6
Cardiac arrest	1/198 (0.5%)	1	0/191 (0%)	0
Myocardial infarction	1/198 (0.5%)	2	1/191 (0.5%)	2
Congestive heart failure	1/198 (0.5%)	2	1/191 (0.5%)	2
Hypotension	4/198 (2%)	4	0/191 (0%)	0
Cardiac death	2/198 (1%)	3	1/191 (0.5%)	3
Gastrointestinal disorders
GI bleed	1/198 (0.5%)	2	1/191 (0.5%)	2
Small bowel obstruction	0/198 (0%)	0	1/191 (0.5%)	1
Immune system disorders
Fever	1/198 (0.5%)	2	1/191 (0.5%)	2
Infections and infestations
Urinary tract infection	1/198 (0.5%)	1	0/191 (0%)	0
Sternal wound infection	1/198 (0.5%)	2	1/191 (0.5%)	2
Cellulitis	1/198 (0.5%)	1	0/191 (0%)	0
Pneumonia	2/198 (1%)	5	3/191 (1.6%)	5
Nervous system disorders
Stroke	5/198 (2.5%)	11	6/191 (3.1%)	11
Renal and urinary disorders
Renal insufficiency	4/198 (2%)	5	1/191 (0.5%)	5
Renal failure	3/198 (1.5%)	5	2/191 (1%)	5
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/198 (1%)	10	8/191 (4.2%)	10
Respiratory failure	8/198 (4%)	14	6/191 (3.1%)	14
Respiratory distress	3/198 (1.5%)	6	3/191 (1.6%)	6
Surgical and medical procedures
Reexploration for bleeding	3/198 (1.5%)	6	3/191 (1.6%)	6
Other (Not Including Serious) Adverse Events
	Magnesium		0.9 % Saline
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	137/198 (69.2%)		109/191 (57.1%)
Blood and lymphatic system disorders
Postoperative bleeding	11/198 (5.6%)		8/191 (4.2%)
Cardiac disorders
Hypotension	11/198 (5.6%)		10/191 (5.2%)
Anemia	16/198 (8.1%)		7/191 (3.7%)
Atrial fibrillation	78/198 (39.4%)		66/191 (34.6%)
Renal and urinary disorders
Renal Insufficiency	12/198 (6.1%)		4/191 (2.1%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	9/198 (4.5%)		14/191 (7.3%)

Limitations/Caveats

[Not Specified]

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.