Trial Outcomes & Findings for Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass (NCT NCT02025621)
NCT ID: NCT02025621
Last Updated: 2018-06-21
Results Overview
The all-cause death at 30 days or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) through Day 5
Recruitment status
COMPLETED
Study phase
PHASE3
Target enrollment
882 participants
Primary outcome timeframe
30 days
Results posted on
2018-06-21
Participant Flow
Participant milestones
| Measure |
Levosimendan
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Overall Study
STARTED
|
442
|
440
|
|
Overall Study
COMPLETED
|
428
|
421
|
|
Overall Study
NOT COMPLETED
|
14
|
19
|
Reasons for withdrawal
| Measure |
Levosimendan
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
1
|
0
|
|
Overall Study
Death
|
0
|
1
|
|
Overall Study
No longer eligible
|
10
|
15
|
|
Overall Study
Surgery initiated before infusion
|
3
|
3
|
Baseline Characteristics
Levosimendan in Patients With Left Ventricular Systolic Dysfunction Undergoing Cardiac Surgery On Cardiopulmonary Bypass
Baseline characteristics by cohort
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
Total
n=849 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
65 years
n=99 Participants
|
65 years
n=107 Participants
|
65 years
n=206 Participants
|
|
Sex: Female, Male
Female
|
81 Participants
n=99 Participants
|
89 Participants
n=107 Participants
|
170 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
347 Participants
n=99 Participants
|
332 Participants
n=107 Participants
|
679 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
White/Caucasian
|
385 Participants
n=99 Participants
|
375 Participants
n=107 Participants
|
760 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Black
|
21 Participants
n=99 Participants
|
23 Participants
n=107 Participants
|
44 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Asian
|
9 Participants
n=99 Participants
|
10 Participants
n=107 Participants
|
19 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
American Indian or Alaska Native
|
2 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
6 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Native Hawaiian or other Pacific Islander
|
1 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
1 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Other
|
5 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
12 Participants
n=206 Participants
|
|
Race/Ethnicity, Customized
Not given
|
5 Participants
n=99 Participants
|
2 Participants
n=107 Participants
|
7 Participants
n=206 Participants
|
|
Region of Enrollment
Canada
|
71 participants
n=99 Participants
|
88 participants
n=107 Participants
|
159 participants
n=206 Participants
|
|
Region of Enrollment
United States
|
357 participants
n=99 Participants
|
333 participants
n=107 Participants
|
690 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: 30 daysPopulation: mITT; population receiving any study drug
The all-cause death at 30 days or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) through Day 5
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Number of Dual Efficacy Endpoint Events
|
56 events
|
48 events
|
PRIMARY outcome
Timeframe: 30 daysPopulation: mITT; population receiving any study drug
Composite of all-cause death (at 30 days), or perioperative nonfatal MI \[CK-MB \>10xULN or \>100 ng/mL, CK-MB \>5xULN or 50 ng/mL with new Q wave (\>0.04 seconds wide in two contiguous leads) or new left bundle branch block)\] (through Day 5), or need for renal dialysis (through Day 30), or use of mechanical assist device (IABP, LVAD or ECMO) following the start of surgery for poor cardiac function despite inotropic support and adequate fluid replacement) (through Day 5)
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Number of Quad Efficacy Endpoint Events
|
105 events
|
103 events
|
SECONDARY outcome
Timeframe: participants will be followed for during the participant's hospital stay up to 30 daysPopulation: mITT; patients that received any study drug
Duration of intensive care unit/critical or coronary care unit (ICU/CCU) length of stay (LOS) in days
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Duration of Intensive Care Unit/Critical or Coronary Care Unit (ICU/CCU) (Days)
|
2.8 days
Interval 1.6 to 4.8
|
2.9 days
Interval 1.8 to 4.9
|
SECONDARY outcome
Timeframe: 5 daysPopulation: mITT; patients receiving any study drug
Use of a mechanical cardiac assist device within 5 days after surgery, two consecutive measurements of low cardiac output (defined as a cardiac output of ≤2.0 liters per minute per square meter of bodysurface area), one measurement of low cardiac output plus the use of two or more inotropes at or beyond 24 hours after surgery, or the use of two or more inotropes at or beyond 24 hours after surgery with the indicated reason being low cardiac output.
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Incidence of Low Cardiac Output Syndrome (LCOS)
|
78 Participants
|
108 Participants
|
SECONDARY outcome
Timeframe: 24 hoursUse of (dobutamine, milrinone, epinephrine, dopamine) associated with index surgical procedure at 24 hours after initiation of surgery
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Postoperative Use of Secondary Inotrope
|
235 Participants
|
264 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 90 daysPopulation: all patients receiving study drug, according to the drug actually received
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Occurrence of All-cause Mortality From Randomization Through Day 90
|
20 Participants
|
30 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 30 daysPopulation: patients receiving study drug, by study drug received
Outcome measures
| Measure |
Levosimendan
n=428 Participants
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 Participants
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Rehospitalization for Any Cause Through Day 30
|
54 Participants
|
48 Participants
|
Adverse Events
Levosimendan
Serious events: 34 serious events
Other events: 238 other events
Deaths: 20 deaths
Placebo
Serious events: 37 serious events
Other events: 232 other events
Deaths: 30 deaths
Serious adverse events
| Measure |
Levosimendan
n=428 participants at risk
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 participants at risk
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Respiratory, thoracic and mediastinal disorders
Aspiration
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Dypnoea
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Haemothorax
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Reproductive system and breast disorders
Hypoxia
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Mediastinal haemorrhage
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pulmonary oedema
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Renal and urinary disorders
Acute kidney injury
|
0.70%
3/428 • Number of events 3 • through Day 30
|
0.71%
3/421 • Number of events 3 • through Day 30
|
|
Renal and urinary disorders
Chronic kidney disease
|
0.47%
2/428 • Number of events 2 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Renal and urinary disorders
Urethral stenosis
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Injury, poisoning and procedural complications
Post procedural haemorrhage
|
0.47%
2/428 • Number of events 2 • through Day 30
|
0.48%
2/421 • Number of events 2 • through Day 30
|
|
Injury, poisoning and procedural complications
Femoral neck fracture
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Injury, poisoning and procedural complications
Postoperative wound complication
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Cardiac disorders
Cardiogenic Shock
|
1.2%
5/428 • Number of events 5 • through Day 30
|
1.2%
5/421 • Number of events 5 • through Day 30
|
|
Cardiac disorders
Cardiac tamponade
|
0.47%
2/428 • Number of events 2 • through Day 30
|
0.48%
2/421 • Number of events 2 • through Day 30
|
|
Cardiac disorders
Pericardial effusion
|
0.23%
1/428 • Number of events 1 • through Day 30
|
1.4%
6/421 • Number of events 6 • through Day 30
|
|
Cardiac disorders
Atrial Fibrilation
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Cardiac disorders
Cardiac Arrest
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Cardiac disorders
Cardiac failure congestive
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Cardiac disorders
Coronary artery dissection
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Cardiac disorders
Hypertensive heart disease
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Cardiac disorders
Ischaemic cardiomyopathy
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Cardiac disorders
Ventricular dysfunction
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
0.23%
1/428 • Number of events 1 • through Day 30
|
1.4%
6/421 • Number of events 6 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Chronic obstructive pulmonary disease
|
0.47%
2/428 • Number of events 2 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Hypercapnia
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Respiratory accidosis
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Gastrointestinal disorders
Constipation
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Gastrointestinal disorders
Erosive oesophagitis
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Gastrointestinal disorders
Gastrointestinal haemorrhage
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Gastrointestinal disorders
Megacolon
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Gastrointestinal disorders
Oesophagitis
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
General disorders
Vomiting
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
General disorders
Multiple organ dysfunction syndrome
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
General disorders
Chest pain
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
General disorders
Ulcer haemorrhage
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Infections and infestations
Catheter site infection
|
0.23%
1/428 • Number of events 1 • through Day 30
|
0.00%
0/421 • through Day 30
|
|
Infections and infestations
Osteomyelitis
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
|
Infections and infestations
Sepsi
|
0.00%
0/428 • through Day 30
|
0.24%
1/421 • Number of events 1 • through Day 30
|
Other adverse events
| Measure |
Levosimendan
n=428 participants at risk
levosimendan 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Levosimendan
|
Placebo
n=421 participants at risk
placebo 0.2 µg/kg/min for first hour, followed by 0.1 µg/kg/min for an additional 23 hours
Placebo: matching placebo
|
|---|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia
|
8.9%
38/428 • Number of events 38 • through Day 30
|
9.0%
38/421 • Number of events 38 • through Day 30
|
|
Cardiac disorders
Anaemia
|
8.2%
35/428 • Number of events 35 • through Day 30
|
5.7%
24/421 • Number of events 24 • through Day 30
|
|
Blood and lymphatic system disorders
Leukocytosis
|
3.7%
16/428 • Number of events 16 • through Day 30
|
5.5%
23/421 • Number of events 23 • through Day 30
|
|
Blood and lymphatic system disorders
Coagulopathy
|
5.1%
22/428 • Number of events 22 • through Day 30
|
2.1%
9/421 • Number of events 9 • through Day 30
|
|
Blood and lymphatic system disorders
Haemorrhagic anaemia
|
2.8%
12/428 • Number of events 12 • through Day 30
|
1.9%
8/421 • Number of events 8 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pleural effusion
|
5.1%
22/428 • Number of events 24 • through Day 30
|
7.1%
30/421 • Number of events 31 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Pneumothorax
|
4.2%
18/428 • Number of events 19 • through Day 30
|
4.5%
19/421 • Number of events 20 • through Day 30
|
|
Respiratory, thoracic and mediastinal disorders
Hypoxia
|
0.47%
2/428 • Number of events 2 • through Day 30
|
2.1%
9/421 • Number of events 9 • through Day 30
|
|
Renal and urinary disorders
Acute kidney injury
|
11.4%
49/428 • Number of events 50 • through Day 30
|
12.1%
51/421 • Number of events 54 • through Day 30
|
|
Renal and urinary disorders
Urinary retention
|
1.6%
7/428 • Number of events 7 • through Day 30
|
3.1%
13/421 • Number of events 13 • through Day 30
|
|
Cardiac disorders
Cardiogenic shock
|
4.0%
17/428 • Number of events 17 • through Day 30
|
3.6%
15/421 • Number of events 15 • through Day 30
|
|
Cardiac disorders
Sinus tachycardia
|
2.1%
9/428 • Number of events 9 • through Day 30
|
1.7%
7/421 • Number of events 7 • through Day 30
|
|
Metabolism and nutrition disorders
Hyponatraemia
|
3.7%
16/428 • Number of events 16 • through Day 30
|
2.1%
9/421 • Number of events 9 • through Day 30
|
|
Metabolism and nutrition disorders
Hyperglycaemia
|
3.5%
15/428 • Number of events 15 • through Day 30
|
1.9%
8/421 • Number of events 9 • through Day 30
|
|
Metabolism and nutrition disorders
Hyperkalaemia
|
2.6%
11/428 • Number of events 11 • through Day 30
|
1.4%
6/421 • Number of events 6 • through Day 30
|
|
Metabolism and nutrition disorders
Fluid overload
|
2.1%
9/428 • Number of events 9 • through Day 30
|
1.7%
7/421 • Number of events 7 • through Day 30
|
|
Psychiatric disorders
Delirium
|
4.4%
19/428 • Number of events 21 • through Day 30
|
2.9%
12/421 • Number of events 13 • through Day 30
|
|
Cardiac disorders
Hypotension
|
36.2%
155/428 • Number of events 155 • through Day 30
|
32.8%
138/421 • Number of events 138 • through Day 30
|
|
Cardiac disorders
Atrial fibrillation/flutter
|
37.1%
159/428 • Number of events 159 • through Day 30
|
31.8%
134/421 • Number of events 134 • through Day 30
|
|
Cardiac disorders
Ventricular tachycardia/fibrillation
|
10.7%
46/428 • Number of events 46 • through Day 30
|
9.7%
41/421 • Number of events 41 • through Day 30
|
|
General disorders
Stroke
|
3.5%
15/428 • Number of events 15 • through Day 30
|
2.9%
12/421 • Number of events 12 • through Day 30
|
Additional Information
Rajendra Mehta, MD Study Principal Investigator
Duke Clinical Research Institute
Phone: 919-668-8971
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place