Congenital Heart DefectsPhase 2MiLe-1NCT02232399
Is Levosimendan Superior to Milrinone Regarding Acute Kidney Injury After Cardiac Surgery for Congenital Heart Disease?
A Phase 2 study testing Levosimendan and Milrinone in people with Congenital Heart Defects, run by Göteborg University at 2 sites in 2 countries.
Trial summary
The aim of the study is to assess the ability of Levosimendan to reduce the postoperative acute kidney injury in pediatric patients undergoing surgery for congenital heart disease (CHDs). Read more about this study
- Who is it for?
- Ages 1 month to 12 months
- Conditions the study is for
- Congenital Heart Defects
- What is being tested?
- Levosimendan and Milrinone
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 2 sitesin 2 countries
- Study dates
- 15 Oct 2014to 25 Apr 2017
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 month to 12 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Provision of informed consent prior to any study specific procedures
- Female and male children between 1 and 12 months of age
- Non-restrictive VSD (corrective surgery)
- Complete AVSD (biventricular repair)
- Tetralogy of Fallot
Who cannot join
- Unbalanced AtrioVentricular Septal Defect or AVSD with cyanosis
- Age less than one month and more than one year
- Acute operation that is unscheduled operation during the first 24 hours after presentation to the department for thoracic surgery
- Mild, moderate, or severe kidney dysfunction and known anatomical anomalies of kidneys
- Liver impairment or disease
- Ongoing infection
Show all 14Show fewer
- Use of nephrotoxic drugs (like ibuprofen, angiotensin-converting-enzyme inhibitors, gentamicin, vancomycin) preoperative or postoperative until first post operative day. Contrast agents whithin 24 hours before operation.
- Use of inhibitors of membrane transport proteins (cimetidine, cetirizine, trimethoprim, probenecid, rifampin and gemfibrosil).
- Allergy to Levosimendan or substance included in the preparation or previous use of Levosimendan.
- Severe arrhythmias needing pace-maker treatment prior to the operation
- Severe cardiac dysfunction needing for treatment with extracorporeal membrane oxygenation (ECMO) prior to the operation.
- Preoperative need for mechanical ventilation and/or inotropic agents.
- Re-operation (open heart surgery). Earlier surgical closure of the arterial duct does not count as an exclusion criteria.
- Prematurity: Gestational age < 30 weeks, irrespective of postpartum age. Gestational age 30-34 weeks if patient is included at postpartum age under 3 months.
Trial locations and contacts
2 sites in 2 countries.
2 sites in 2 countries
Finland1 site
Children´s Hospital, Helsinki University Central Hospital
Helsinki, FIN-00029 HYKS
Sweden1 site
Queen Silvia Children´s Hospital
Gothenburg, Västra Götaland County, 416 85
About this study
Official title: The Prophylactic Effect of Levosimendan in Reducting Acute Kidney Injury Postoperatively in Pediatric Patients Undergoing Corrective Heart Surgery
The aim of the study is to assess the ability of Levosimendan to reduce the postoperative acute kidney injury in pediatric patients undergoing surgery for congenital heart disease (CHDs).
Read the detailed description
Young children, between the age of 1 to 12 months, with congenital heart disease in need of elective heart surgery will be included in this study.
The trial will contain two study groups, 35 patients in each. One group will receive Levosimendan and the second group will receive Milrinone as a heart muscle-strengthening agent during and after the operation. Milrinone is currently used as the drug of choice in many pediatric cardiac surgery centers. It remains to see if Levosimendan can exert a kidney protecting function in addition to its heart muscle-strengthening properties.
The primary objective of this study is to investigate the preventive effect of Levosimendan on postoperative acute kidney injury in pediatric patients undergoing surgery for their CHDs. Creatinine levels postoperatively will be the primary endpoint. Creatinine, the common marker of kidney injury, will be measured daily.
The treatment with Levosimendan or Milrinone will be started during the operation (after initiation of cardiopulmonary bypass) and will last 24 hours. Blood samples will be obtained at six occasions perioperatively. Patients will be followed 4 days after termination of treatment (totally 5 days).
The duration of study will be 30 days (24 hours treatment + 4 days follow up + 30-days-mortality registration).
Creatinine is the primary outcome in this study. Inflammatory biomarkers and other relevant biomarkers will comprise the secondary outcome variables.
- Conditions
- Congenital Heart Defects
- Being tested
- Levosimendan, Milrinone
- Medical subject headings
- Heart Defects, Congenital
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Also called Simdax
The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.
MilrinoneDrug
Also called Corotrop
The drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Milrinone | Active comparator | 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 Receives: Drug: Milrinone |
| Levosimendan | Experimental | 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 Receives: Drug: Levosimendan |
What is being measured
The primary outcome is the main question the study is designed to answer.
S-creatinine
The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.
Measured: One day after cardiac surgery
Secondary outcomes (2)
Acute Kidney Injury (AKI)
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)
Measured: Two days (second postoperative day)
30 Days Mortality
Mortality at 30th day
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Sep 2014 (estimated)
- Study start15 Oct 2014
- Primary completion25 Apr 2017
- Study completion25 Apr 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Congenital Heart DefectsStudies of the same condition, open and under way.
- More trials run by Göteborg UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 72 participants (actual)
Sponsor and investigators
- Lead sponsor
- Göteborg University
- Sponsor type
- University, hospital or other
- Collaborators
- Helsinki University Central Hospital
- Responsible party
- Principal investigator, Albert Castellheim, Göteborg University
- Investigators
- Albert Castellheim, MD, PhD, Principal investigator, Queen Silvia Children´s Hospital, Department of anesthesia and intensive careHåkan Wåhlander, MD, PhD, Study chair, Queen Silvia Children´s Hospital, Department of pediatric cardiologyBirgitta Romlin, MD, PhD, Study chair, Queen Silvia Children´s Hospital, Department of anesthesiology and intensive careElin Thorlacius, MD, Study chair, Queen Silvia Children´s Hospital, Department of anesthesiology and intensive careSven-Erik Ricksten, MD, PhD, Study chair, Sahlgrenska University Hospital, Department of anesthesiology and intensive care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02232399
- Sponsor's protocol ID
- MiLe-1
- Other IDs
- 2013-003105-25
- Acronym
- MiLe-1
- Status last verified
- Mar 2024
- First submitted
- 2 Sep 2014
- Last updated
- 26 Mar 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Thorlacius EM, Vistnes M, Ojala T, Keski-Nisula J, Molin M, Romlin BS, Synnergren M, Ricksten SE, Wahlander H, Castellheim A. Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data. Pediatr Crit Care Med. 2021 Jul 1;22(7):e402-e409. doi: 10.1097/PCC.0000000000002712.
PubMed 33739957
Study at a glance
From the registry record, last updated by the sponsor on 26 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Prophylactic Effect of Levosimendan in Reducting Acute Kidney Injury Postoperatively in Pediatric Patients Undergoing Corrective Heart Surgery
- ClinicalTrials.gov ID
- NCT02232399
- Acronym / sponsor ID
- MiLe-1 / MiLe-1
- Conditions
- Congenital Heart Defects
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 72 participants (actual)
- Lead sponsor
- Göteborg UniversityUniversity, hospital or other
- Collaborators
- Helsinki University Central Hospital
- Study start
- 15 Oct 2014 (actual)
- Primary completion
- 25 Apr 2017 (actual)
- Study completion
- 25 Apr 2017 (actual)
- First posted
- 5 Sep 2014 (estimated)
- Results
- Posted 26 Mar 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of the study is to assess the ability of Levosimendan to reduce the postoperative acute kidney injury in pediatric patients undergoing surgery for congenital heart disease (CHDs).
Detailed description
Young children, between the age of 1 to 12 months, with congenital heart disease in need of elective heart surgery will be included in this study.
The trial will contain two study groups, 35 patients in each. One group will receive Levosimendan and the second group will receive Milrinone as a heart muscle-strengthening agent during and after the operation. Milrinone is currently used as the drug of choice in many pediatric cardiac surgery centers. It remains to see if Levosimendan can exert a kidney protecting function in addition to its heart muscle-strengthening properties.
The primary objective of this study is to investigate the preventive effect of Levosimendan on postoperative acute kidney injury in pediatric patients undergoing surgery for their CHDs. Creatinine levels postoperatively will be the primary endpoint. Creatinine, the common marker of kidney injury, will be measured daily.
The treatment with Levosimendan or Milrinone will be started during the operation (after initiation of cardiopulmonary bypass) and will last 24 hours. Blood samples will be obtained at six occasions perioperatively. Patients will be followed 4 days after termination of treatment (totally 5 days).
The duration of study will be 30 days (24 hours treatment + 4 days follow up + 30-days-mortality registration).
Creatinine is the primary outcome in this study. Inflammatory biomarkers and other relevant biomarkers will comprise the secondary outcome variables.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, care provider)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Milrinone | Active comparator | Drug: MilrinoneIn 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 |
| Levosimendan | Experimental | Drug: LevosimendanIn 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 |
Who may qualify
- Ages
- 1 month to 12 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (5 listed)
- Provision of informed consent prior to any study specific procedures
- Female and male children between 1 and 12 months of age
- Non-restrictive VSD (corrective surgery)
- Complete AVSD (biventricular repair)
- Tetralogy of Fallot
Key exclusion criteria (14 listed)
- Unbalanced AtrioVentricular Septal Defect or AVSD with cyanosis
- Age less than one month and more than one year
- Acute operation that is unscheduled operation during the first 24 hours after presentation to the department for thoracic surgery
- Mild, moderate, or severe kidney dysfunction and known anatomical anomalies of kidneys
- Liver impairment or disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| LevosimendanAlso: SimdaxThe drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours. | Drug | Levosimendan |
| MilrinoneAlso: CorotropThe drug infusion will be started after initiation of cardiopulmonary bypass and will continue for 24 hours. | Drug | Milrinone |
Primary outcome
S-creatinine
Time frame: One day after cardiac surgery
The primary outcome variable was the absolute value of serum creatinine data on postoperative day 1.
2 secondary outcomes
Acute Kidney Injury (AKI)
Time frame: Two days (second postoperative day)
30 Days Mortality
Time frame: 30 days
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Mar 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 33739957Thorlacius EM, Vistnes M, Ojala T, Keski-Nisula J, Molin M, Romlin BS, Synnergren M, Ricksten SE, Wahlander H, Castellheim A. Levosimendan Versus Milrinone and Release of Myocardial Biomarkers After Pediatric Cardiac Surgery: Post Hoc Analysis of Clinical Trial Data. Pediatr Crit Care Med. 2021 Jul 1;22(7):e402-e409. doi: 10.1097/PCC.0000000000002712.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Albert Castellheim, MD, PhD principal investigator
Queen Silvia Children´s Hospital, Department of anesthesia and intensive care
Håkan Wåhlander, MD, PhD study chair
Queen Silvia Children´s Hospital, Department of pediatric cardiology
Birgitta Romlin, MD, PhD study chair
Queen Silvia Children´s Hospital, Department of anesthesiology and intensive care
2 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Levosimendan and Milrinone in people with Congenital Heart Defects, run by Göteborg University at 2 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Mar 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Finland, Sweden. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 26 Mar 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
S-creatinine (time frame: One day after cardiac surgery). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02232399, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Mar 2024.