Trial Outcomes & Findings for Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial (NCT NCT01369069)

Last Updated: 2019-12-23

Results Overview

Favorable for the primary efficacy outcome is defined as modified Rankin Scale (mRS) score of 0 in patients with mild stroke (baseline NIHSS 3-7), mRS 0 or 1 in patients with moderate stroke (baseline NIHSS 8-14), and mRS 0, 1 or 2 in patients with severe stroke (baseline NIHSS 15-22) at 90 days with a pre-specified range of acceptable days of 76 -120 days. The mRS is a stroke outcome scale used to assess functional status after stroke. It consists of seven levels (0-6) where 0 indicates no residual symptoms at all, 5 indicates severe disability and 6 indicates death. The person collecting the mRS score was to be blinded to the participant's treatment group assignment.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

1151 participants

Primary outcome timeframe

90 days (-14/+30 days)

Results posted on

2019-12-23

Participant Flow

Between April 2012 and August 2018, a total of 70 United States sites were included in the trial, and 63 sites enrolled at least one patient.

28977 patients were excluded after screening. Of those, 27344 did not meet eligibility criteria; 1156 were unable to provide informed consent or refused participation; 342 had other reasons and 135 did not specify a reason.

Participant milestones

Participant milestones
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Overall Study STARTED	581	570
Overall Study COMPLETED	564	554
Overall Study NOT COMPLETED	17	16

Reasons for withdrawal

Reasons for withdrawal
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Overall Study Lost to Follow-up	8	9
Overall Study Withdrawal by Subject	9	7

Baseline Characteristics

Stroke Hyperglycemia Insulin Network Effort (SHINE) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.	Total n=1151 Participants Total of all reporting groups
Age, Continuous	66 years n=5 Participants	66 years n=7 Participants	66 years n=5 Participants
Sex: Female, Male Female	260 Participants n=5 Participants	264 Participants n=7 Participants	524 Participants n=5 Participants
Sex: Female, Male Male	321 Participants n=5 Participants	306 Participants n=7 Participants	627 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	87 Participants n=5 Participants	91 Participants n=7 Participants	178 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	460 Participants n=5 Participants	449 Participants n=7 Participants	909 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	34 Participants n=5 Participants	30 Participants n=7 Participants	64 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	2 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) Asian	12 Participants n=5 Participants	18 Participants n=7 Participants	30 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	2 Participants n=5 Participants	5 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) Black or African American	180 Participants n=5 Participants	154 Participants n=7 Participants	334 Participants n=5 Participants
Race (NIH/OMB) White	366 Participants n=5 Participants	368 Participants n=7 Participants	734 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	21 Participants n=5 Participants	23 Participants n=7 Participants	44 Participants n=5 Participants
Final diagnosis Ischemic stroke	542 Participants n=5 Participants	524 Participants n=7 Participants	1066 Participants n=5 Participants
Final diagnosis Transient ischemic attack	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants
Final diagnosis Other	31 Participants n=5 Participants	34 Participants n=7 Participants	65 Participants n=5 Participants
Thrombolysis or Thrombectomy Intravenous tPA	372 Participants n=5 Participants	353 Participants n=7 Participants	725 Participants n=5 Participants
Thrombolysis or Thrombectomy Mechanical treatment	74 Participants n=5 Participants	72 Participants n=7 Participants	146 Participants n=5 Participants
Thrombolysis or Thrombectomy Intraarterial drug therapy	14 Participants n=5 Participants	21 Participants n=7 Participants	35 Participants n=5 Participants
Thrombolysis or Thrombectomy None	121 Participants n=5 Participants	124 Participants n=7 Participants	245 Participants n=5 Participants
Medical History Hypertension	513 Participants n=5 Participants	502 Participants n=7 Participants	1015 Participants n=5 Participants
Medical History Diabetes mellitus (Type 2)	468 Participants n=5 Participants	455 Participants n=7 Participants	923 Participants n=5 Participants
Medical History Hyperlipidemia	350 Participants n=5 Participants	327 Participants n=7 Participants	677 Participants n=5 Participants
Medical History Coronary artery disease	159 Participants n=5 Participants	167 Participants n=7 Participants	326 Participants n=5 Participants
Medical History Atrial fibrillation	124 Participants n=5 Participants	106 Participants n=7 Participants	230 Participants n=5 Participants
Medical History Previous Ischemic stroke	104 Participants n=5 Participants	99 Participants n=7 Participants	203 Participants n=5 Participants
Medical History Previous large vessel atherosclerosis	42 Participants n=5 Participants	39 Participants n=7 Participants	81 Participants n=5 Participants
Eligibility POC blood glucose (mg/dL)	188 mg/dL n=5 Participants	187 mg/dL n=7 Participants	187.5 mg/dL n=5 Participants
Baseline NIHSS at randomization	7 NIHSS score range: 0 to 42 n=5 Participants	7 NIHSS score range: 0 to 42 n=7 Participants	7 NIHSS score range: 0 to 42 n=5 Participants
Baseline NIHSS category at randomization Mild (NIHSS 3-7)	291 Participants n=5 Participants	291 Participants n=7 Participants	582 Participants n=5 Participants
Baseline NIHSS category at randomization Moderate (NIHSS 8-14)	177 Participants n=5 Participants	158 Participants n=7 Participants	335 Participants n=5 Participants
Baseline NIHSS category at randomization Severe (NIHSS 15-22)	113 Participants n=5 Participants	121 Participants n=7 Participants	234 Participants n=5 Participants

PRIMARY outcome

Timeframe: 90 days (-14/+30 days)

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Number of Participants With a Favorable Modified Rankin Scale (Yes/No)	119 Participants	123 Participants

PRIMARY outcome

Timeframe: 72 hours

Severe hypoglycemia (blood glucose \< 40mg/dL) is the primary safety outcome and will be measured during the 72 hour treatment period.

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Number of Participants With Severe Hypoglycemia (Blood Glucose < 40mg/dL)	15 Participants	0 Participants

SECONDARY outcome

Timeframe: Follow up (Max 164 days)

The NIHSS (National Institutes of Health Stroke Scale) score ranges from 0 to 42, with higher scores indicating greater neurological deficits. A favorable NIHSS was defined as a score of 0 or 1 on the NIHSS at 90 days post randomization.

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=348 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=371 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Number of Participants With a Favorable NIHSS	152 Participants	166 Participants

SECONDARY outcome

Timeframe: Follow up (Max 164 days)

Favorable outcomes for the Barthel Index was defined as a score of 95-100 on the BI at 90 days post randomization. Barthel - Barthel Index for Activities of Daily Living (ADL) assesses functional independence, generally in stroke patients. Scores range from 0-100 with higher scores indicating greater ability to perform activities of daily living.

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=491 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=477 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Number of Participants With a Favorable Barthel Index	271 Participants	261 Participants

SECONDARY outcome

Timeframe: Follow up (Max 164 days)

Stroke Specific Quality of Life. Scores range from 1-5 with higher scores indicating better quality of life

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=442 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=432 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Stroke Specific Quality of Life (SSQOL)	3.75 score on a scale Interval 2.98 to 4.4	3.69 score on a scale Interval 3.02 to 4.46

OTHER_PRE_SPECIFIED outcome

Timeframe: 90 days (+30 days)

Death from any cause

Outcome measures

Outcome measures
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 Participants The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 Participants This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Death	54 Participants	65 Participants

Adverse Events

IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL

Serious events: 209 serious events

Other events: 384 other events

Deaths: 54 deaths

Sub Q Insulin to Keep Glucose Less Than 180 mg/dL

Serious events: 198 serious events

Other events: 134 other events

Deaths: 65 deaths

Serious adverse events

Other adverse events

Additional Information

Karen C. Johnston, MD

University of Virginia

Phone: 434 924-5323

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Serious adverse events
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 participants at risk The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 participants at risk This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Blood and lymphatic system disorders Anaemia	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Blood and lymphatic system disorders Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Blood and lymphatic system disorders Thrombocytopenia	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Acute coronary syndrome	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Acute myocardial infarction	1.0% 6/581 • Number of events 6 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Atrial fibrillation	1.4% 8/581 • Number of events 9 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.70% 4/570 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Atrial flutter	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Bradycardia	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardiac arrest	1.2% 7/581 • Number of events 10 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	1.2% 7/570 • Number of events 7 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardiac failure	0.52% 3/581 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.88% 5/570 • Number of events 5 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardiac failure congestive	0.69% 4/581 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardio-respiratory arrest	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardiogenic shock	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Ischaemic cardiomyopathy	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Myocardial infarction	1.0% 6/581 • Number of events 6 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.88% 5/570 • Number of events 5 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Supraventricular tachycardia	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Ventricular tachycardia	0.17% 1/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Ear and labyrinth disorders Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Eye disorders Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Abdominal pain	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Dysphagia	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Gastric haemorrhage	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Gastrointestinal disorder	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.34% 2/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Haematemesis	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Other (combined AEs happened only once)	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	1.1% 6/570 • Number of events 6 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Small intestinal obstruction	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Chest pain	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Device occlusion	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Multi-organ failure	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Other (combined AEs happened only once)	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Pyrexia	0.17% 1/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Sudden death	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Hepatobiliary disorders Cholecystitis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Hepatobiliary disorders Other (combined AEs happened only once)	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Immune system disorders Other (combined AEs happened only once)	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Bacteraemia	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Cellulitis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Clostridium difficile colitis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).

Other adverse events
Measure	IV Insulin Drip With Target Glucose 80 mg/dL - 130 mg/dL n=581 participants at risk The intervention arm will have a targeted glucose concentration of 80-130 mg/dL. IV insulin drip will be titrated to keep glucose concentration in this range. IV insulin to maintain target glucose concentration of 80-130 mg/dL: Intervention is to keep glucose concentration 80-130 mg/dL for up to 72 hours after randomization. IV insulin drip will be used to maintain glucose target.	Sub Q Insulin to Keep Glucose Less Than 180 mg/dL n=570 participants at risk This standard care arm will get sub q insulin sliding scale to keep glucose concentration less than 180 mg/dL Standard Care control - sliding scale insulin to keep glucose less than 180 mg/dL: Sliding scale sub q insulin given will be given up to 4 times per day based on glucose concentration. It will be given only if glucose concentration greater than or equal to 180 mg/dL.
Blood and lymphatic system disorders Anaemia	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	1.1% 6/570 • Number of events 6 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Blood and lymphatic system disorders Leukocytosis	0.69% 4/581 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Acute myocardial infarction	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Atrial fibrillation	1.5% 9/581 • Number of events 9 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	1.6% 9/570 • Number of events 9 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Bradycardia	0.52% 3/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Cardiac failure congestive	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Ischaemic cardiomyopathy	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Other (combined AEs happened only once)	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Supraventricular tachycardia	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Cardiac disorders Ventricular tachycardia	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Congenital, familial and genetic disorders Other (combined AEs happened only once)	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Endocrine disorders Hypothyroidism	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Eye disorders Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Dysphagia	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Nausea	0.69% 4/581 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Other (combined AEs happened only once)	0.52% 3/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Gastrointestinal disorders Vomiting	0.86% 5/581 • Number of events 6 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	1.4% 8/570 • Number of events 8 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Catheter site haematoma	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Chest pain	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Other (combined AEs happened only once)	0.52% 3/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Pain	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
General disorders Pyrexia	1.2% 7/581 • Number of events 7 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.88% 5/570 • Number of events 5 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Hepatobiliary disorders Other (combined AEs happened only once)	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Immune system disorders Hypersensitivity	0.00% 0/581 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Cellulitis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Endocarditis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Infection	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Other (combined AEs happened only once)	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.70% 4/570 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Sepsis	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Infections and infestations Urinary tract infection	2.1% 12/581 • Number of events 12 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.88% 5/570 • Number of events 5 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Injury, poisoning and procedural complications Contusion	0.52% 3/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.00% 0/570 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Injury, poisoning and procedural complications Fall	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.53% 3/570 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Injury, poisoning and procedural complications Other (combined AEs happened only once)	0.69% 4/581 • Number of events 4 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Investigations Activated partial thromboplastin time prolonged	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Investigations Blood chloride increased	0.52% 3/581 • Number of events 3 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.35% 2/570 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Investigations Blood cholesterol increased	0.34% 2/581 • Number of events 2 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Investigations Blood creatinine decreased	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).
Investigations Blood potassium decreased	0.17% 1/581 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).	0.18% 1/570 • Number of events 1 • Non-serious adverse events were assessed and reported through the treatment period (up to 72 hours). Serious adverse events were reported throughout the study period (randomization through end of study; end of study was 90 days post randomization or earlier if a participant died or withdrew consent).