Trial Outcomes & Findings for Glutamate for Metabolic Intervention in Coronary Surgery II (NCT NCT02592824)

NCT ID: NCT02592824

Last Updated: 2023-12-04

Results Overview

Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery. In the first GLUTAMICS trial a good agreement between hemodynamic criteria for postoperative heart failure and postoperative NT-proBNP was found.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 321 participants
• Primary outcome timeframe: from the day before surgery to the third postoperative day
• Results posted on: 2023-12-04

Participant Flow

321 patients gave written informed consent. 7 patients were not randomized ( change of procedure n=2; forgetfulness n=5)

Participant milestones

Measure	Intravenous Glutamate Infusion Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Overall Study STARTED	155	159
Overall Study COMPLETED	148	155
Overall Study NOT COMPLETED	7	4

Reasons for withdrawal

Measure	Intravenous Glutamate Infusion Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Overall Study Protocol Violation	5	3
Overall Study Lost to Follow-up	2	1

Baseline Characteristics

Glutamate for Metabolic Intervention in Coronary Surgery II

Baseline characteristics by cohort

Measure	Intravenous Glutamate Infusion n=148 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Total n=303 Participants Total of all reporting groups
Age, Continuous	73 years STANDARD_DEVIATION 7 • n=5 Participants	75 years STANDARD_DEVIATION 7 • n=7 Participants	74 years STANDARD_DEVIATION 7 • n=5 Participants
Sex: Female, Male Female	36 Participants n=5 Participants	43 Participants n=7 Participants	79 Participants n=5 Participants
Sex: Female, Male Male	112 Participants n=5 Participants	112 Participants n=7 Participants	224 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	148 Participants n=5 Participants	155 Participants n=7 Participants	303 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment Sweden	148 participants n=5 Participants	155 participants n=7 Participants	303 participants n=5 Participants
NTproBNP ng/L	2680 ng/L STANDARD_DEVIATION 4595 • n=5 Participants	2354 ng/L STANDARD_DEVIATION 3124 • n=7 Participants	2513 ng/L STANDARD_DEVIATION 3909 • n=5 Participants

PRIMARY outcome

Timeframe: from the day before surgery to the third postoperative day

Population: Incomlete sampling of NT-proBNP in the Glutamate infusion group (n=3) and Saline infusion group (n=5).

Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery.

In the first GLUTAMICS trial a good agreement between hemodynamic criteria for postoperative heart failure and postoperative NT-proBNP was found.

Outcome measures

Measure	Intravenous Glutamate Infusion n=145 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=150 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Postoperative Increase of Plasma NT-proBNP	5390 ng/L Standard Deviation 5396	6452 ng/L Standard Deviation 5215

SECONDARY outcome

Timeframe: first postoperative day

Postoperative NT-proBNP reflects postoperative myocardial dysfunction.

Outcome measures

Measure	Intravenous Glutamate Infusion n=148 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=153 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Postoperative Plasma Level of NT-proBNP	4438 ng/L Standard Deviation 4879	4420 ng/L Standard Deviation 4236

SECONDARY outcome

Timeframe: third postoperative day

Postoperative NT-proBNP reflects postoperative myocardial dysfunction.

Outcome measures

Measure	Intravenous Glutamate Infusion n=145 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=150 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Postoperative Plasma Level of NT-proBNP	8055 ng/L Standard Deviation 7546	8804 ng/L Standard Deviation 6606

SECONDARY outcome

Timeframe: within 24 hours from surgery

Postoperative stroke was defined as neurological or cognitive deficit with a cerebral injury verified on (Computed Tomography) CT-scan. All suspected cases of stroke underwent CT-scan.

Stroke within 24 h of surgery was defined as a stroke that occurred within 24 h of surgery or signs of a stroke, when first assessable in deeply sedated patients on a ventilator.

Outcome measures

Measure	Intravenous Glutamate Infusion n=148 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Number of Participants With Incidence of Stroke	0 Participants	4 Participants

SECONDARY outcome

Timeframe: up to 30 days

Postoperative mortality was defined as mortality within 30 days of surgery.

Outcome measures

Measure	Intravenous Glutamate Infusion n=148 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Incidence of Mortality	1 Participants	6 Participants

SECONDARY outcome

Timeframe: within 24 hours from infusion

suspected unexpected serious adverse reaction

Outcome measures

Measure	Intravenous Glutamate Infusion n=148 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Incidence of Unexpected Adverse Events	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: preoperative, first and third postoperative day

Exploratory assessment of plasma-Copeptin related to NT-proBNP

Outcome measures

Outcome data not reported

POST_HOC outcome

Timeframe: from preoperative level to the third postoperative day

Postoperative increase of NT-proBNP reflects postoperative myocardial dysfunction sustained in association with surgery. NT-proBNP usually peaks on the third to fourth postoperative day after coronary artery bypass surgery.

Previous observations suggest a blunted effect of glutamate in diabetic hearts.

Outcome measures

Measure	Intravenous Glutamate Infusion n=75 Participants Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=83 Participants Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Postoperative Increase of Plasma NT-proBNP in Patients Without Diabetes	4503 ng/L Standard Deviation 4846	6825 ng/L Standard Deviation 5671

Adverse Events

Intravenous Glutamate Infusion

Serious events: 65 serious events

Other events: 31 other events

Deaths: 1 deaths

Intravenous Saline Infusion

Serious events: 79 serious events

Other events: 31 other events

Deaths: 6 deaths

Serious adverse events

Measure	Intravenous Glutamate Infusion n=148 participants at risk Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 participants at risk Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Surgical and medical procedures Postoperative Atrial Fibrillation	20.9% 31/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	25.2% 39/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure
Surgical and medical procedures Acute Kidney Injury	17.6% 26/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	25.8% 40/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure
Surgical and medical procedures Reoperation for bleeding	7.4% 11/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	11.0% 17/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure
Surgical and medical procedures Periperative myocardial injury	13.5% 20/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	11.6% 18/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure
Nervous system disorders Postoperative Stroke	3.4% 5/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	4.5% 7/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure

Other adverse events

Measure	Intravenous Glutamate Infusion n=148 participants at risk Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. glutamate infusion: Intravenous infusion of 0.125M L-glutamic acid solution at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.	Intravenous Saline Infusion n=155 participants at risk Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate. saline infusion: Intravenous infusion of saline at a rate of 1.65 ml/kg BW and hour commencing at or up to 20 minutes before the release of aortic cross-clamp. The infusion is continued for two hours after declamping the aorta after which an additional 50 ml is given at a halved infusion rate.
Surgical and medical procedures Postoperative Atrial fibrillation	20.9% 31/148 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure	20.0% 31/155 • 30 days Adverse events agree with clinicaltrials.gov definitions but are mainly related to the surgical procedure

Additional Information

Dr Jonas Holm

Linköping University Hospital

Phone: +46101034498

Email: jonas.holm@regionostergotland.se

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place