Trial Outcomes & Findings for Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease? (NCT NCT02232399)

NCT ID: NCT02232399

Last Updated: 2024-03-26

Results Overview

The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 72 participants
• Primary outcome timeframe: One day after cardiac surgery
• Results posted on: 2024-03-26

Participant Flow

Assessed for eligibility (n= 123) Excluded (n=51) * Lack of informed consent (n=15) * Other exclusion criteria (n=21) * Study personnel not available (n=14) * Patient moved to another center (n=1) Randomized (n= 72)

Participant milestones

Measure	Milrinone Allocated to milrinone (n=39) • Received allocated intervention (n=39) Did not receive allocated intervention (n=0)	Levosimendan Allocated to levosimendan (n=33) * Received allocated intervention (n=32) * Did not receive allocated intervention (n=1, consent withdrawn)
Overall Study STARTED	39	33
Overall Study COMPLETED	38	32
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Measure	Milrinone Allocated to milrinone (n=39) • Received allocated intervention (n=39) Did not receive allocated intervention (n=0)	Levosimendan Allocated to levosimendan (n=33) * Received allocated intervention (n=32) * Did not receive allocated intervention (n=1, consent withdrawn)
Overall Study Adverse Event	1	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Race and Ethnicity were not collected from any participant.

Baseline characteristics by cohort

Measure	Milrinone n=38 Participants In this arm the patients will receive Milrinone as an inotrope agent. Concentration: 0.2 mg/mL Infusion rate: 0.12 mL / kg / hr = Dose delivered 0.4 μg / kg / min --- Bolus dose: 1.44 ml / kg / hr in ten minutes (a maximum volume 0.24 ml / kg) = 48 μg / kg Milrinone: The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.	Levosimendan n=32 Participants In this arm the patients will receive Levosimendan as an inotrope agent. Concentration: 0.05 mg/mL Infusion rate: 0.12 mL / kg / hr = Dose delivered 0.1 μg / kg / min --- Bolus dose: 1.44 ml / kg / hr in ten minutes (a maximum volume 0.24 ml / kg) = 12 μg/kg Levosimendan: The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.	Total n=70 Participants Total of all reporting groups
Age, Continuous	5.6 Months STANDARD_DEVIATION 2.7 • n=38 Participants	5.9 Months STANDARD_DEVIATION 2.9 • n=32 Participants	5.6 Months STANDARD_DEVIATION 2.8 • n=70 Participants
Age, Categorical <=18 years	38 Participants n=38 Participants	32 Participants n=32 Participants	70 Participants n=70 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=38 Participants	0 Participants n=32 Participants	0 Participants n=70 Participants
Age, Categorical >=65 years	0 Participants n=38 Participants	0 Participants n=32 Participants	0 Participants n=70 Participants
Sex: Female, Male Female	20 Participants n=38 Participants	16 Participants n=32 Participants	36 Participants n=70 Participants
Sex: Female, Male Male	18 Participants n=38 Participants	16 Participants n=32 Participants	34 Participants n=70 Participants
Race and Ethnicity Not Collected	—	—	0 Participants Race and Ethnicity were not collected from any participant.
Region of Enrollment Sweden	14 participants n=38 Participants	18 participants n=32 Participants	32 participants n=70 Participants
Region of Enrollment Finland	24 participants n=38 Participants	14 participants n=32 Participants	38 participants n=70 Participants
S-Creatinine	23.9 μmole/L STANDARD_DEVIATION 6.1 • n=38 Participants	25.9 μmole/L STANDARD_DEVIATION 5.9 • n=32 Participants	24.5 μmole/L STANDARD_DEVIATION 6.0 • n=70 Participants

PRIMARY outcome

Timeframe: One day after cardiac surgery

The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.

Outcome measures

Measure	Milrinone n=38 Participants Patients who received milrionen	Levosimendan n=32 Participants Patients who received levosimendan
S-creatinine Preoperative	23.9 μmol/L Standard Deviation 6.1	25.9 μmol/L Standard Deviation 5.9
S-creatinine Postop day 1	33.7 μmol/L Standard Deviation 12.9	34.2 μmol/L Standard Deviation 2.0

SECONDARY outcome

Timeframe: Two days (second postoperative day)

Secondary outcomes included the occurrence rate of AKI, defined as a 50% rise in serum creatinine, or more, within 48 hours after surgery. All stages of AKI (stage 1 and stage 2 and stage 3)

Outcome measures

Measure	Milrinone n=38 Participants Patients who received milrionen	Levosimendan n=32 Participants Patients who received levosimendan
Acute Kidney Injury (AKI)	15 Participants	15 Participants

SECONDARY outcome

Timeframe: 30 days

Mortality at 30th day

Outcome measures

Measure	Milrinone n=38 Participants Patients who received milrionen	Levosimendan n=32 Participants Patients who received levosimendan
30 Days Mortality	0 participants	0 participants

Adverse Events

Milrinone

Serious events: 6 serious events

Other events: 11 other events

Deaths: 0 deaths

Levosimendan

Serious events: 9 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Measure	Milrinone n=38 participants at risk Patients who received milrinone	Levosimendan n=32 participants at risk Patients who received levosimendan
Cardiac disorders Arrhythmia	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Cardiac disorders Pericardial fluid and sepsis	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Cardiac disorders Pericard effusion	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Infections and infestations Verified bacterial sepsis	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Cardiac disorders Closure of another small VSD + tricuspid valve plasty + permanent pacemaker due to total AV-block	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Cardiac disorders Readmission for pericardal fluid drainage	2.6% 1/38 • Number of events 1 • Up to 30 days	0.00% 0/32 • Up to 30 days
Cardiac disorders Readmission	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Cardiac disorders Re-operation and dialysis post re-operation	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Cardiac disorders Enalapril caused prolonged hospitalisation	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Infections and infestations Fever and diarrea	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Infections and infestations Upper respiratory tract infection	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Cardiac disorders AV block III	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Infections and infestations Blood culture verified S. aureus sepsis	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Cardiac disorders Postoperative AV-block	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days
Nervous system disorders hydrocephalus and seizure	0.00% 0/38 • Up to 30 days	3.1% 1/32 • Number of events 1 • Up to 30 days

Other adverse events

Measure	Milrinone n=38 participants at risk Patients who received milrinone	Levosimendan n=32 participants at risk Patients who received levosimendan
Nervous system disorders Inotropic score > 20	10.5% 4/38 • Up to 30 days	9.4% 3/32 • Up to 30 days
Cardiac disorders Junctional ectopic tachycardia	18.4% 7/38 • Up to 30 days	9.4% 3/32 • Up to 30 days
Cardiac disorders Third-degree atrioventricular block	0.00% 0/38 • Up to 30 days	6.2% 2/32 • Up to 30 days

Additional Information

Prof. Albert Gyllencreutz Castellheim

University of Gothenburg

Phone: +46708979820

Email: albert.castellheim@gu.se

Results disclosure agreements

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