Heart Failure, DiastolicNCT02408003
Changes in Cardiac Deformation Following Physiologic Alterations and Inotropic Support.
A study testing Levosimendan and Milrinone in people with Heart Failure, Diastolic and Aortic Valve Stenosis, run by Sahlgrenska University Hospital at 1 site in Sweden.
Trial summary
The investigators want to compare the effects of two drugs, levosimendan and milrinone, on cardiac muscle, both in terms of contractility and relaxation. Half of the participants will be randomized to each drug. The effects will be measured through echocardiographic deformation analyses. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure, Diastolic, Aortic Valve Stenosis, Monitoring, Physiologic
- 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
- 30 participants
- Where
- 1 siteSweden
- Study dates
- Mar 2014to May 2017
- Phase
- Interventional
- Are there results?
- None posted in the registry
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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject has aortic valve stenosis
- Subject is scheduled for open heart aortic valve replacement with or without simultaneous coronary artery bypass grafting
Who cannot join
- Less than normal systolic function, defined as ejection fraction less than 0,5
- Non-sinus rhythm
- Any major surgical complication
- Problems understanding the informed consent
Trial locations and contacts
1 site in 1 country.
Sweden1 site
Thoraxoperation/TIVA, Sahlgrenska universitetssjukhuset
Gothenburg, 413 45
About this study
Official title: What Are the Changes in Cardiac Deformation Variables and Hemodynamic Parameters Following Changes in Cardiac Loading Conditions and After Administration of Two Different Inotropic Drugs.
The investigators want to compare the effects of two drugs, levosimendan and milrinone, on cardiac muscle, both in terms of contractility and relaxation. Half of the participants will be randomized to each drug. The effects will be measured through echocardiographic deformation analyses.
Since deformation analyses could be dependent on different loading conditions of the heart, a second purpose of the study is to investigate the changes on deformation parameters after applied changes in preload and afterload, but also heart rate.
Read the detailed description
Aortic stenosis is associated with myocardial hypertrophy and diastolic dysfunction. In patients undergoing open aortic valve replacement surgery due to stenosis, the investigators want to compare the effect on myocardial relaxation between two commonly used drugs, levosimendan and milrinone, using catheter-based measurements in combination with echocardiographic evaluation.
Standard anaesthesia and surgical care for these patients is performed. After surgery is completed and the participant is transferred to the intensive care unit, the studies are performed during general anaesthesia and the participants still connected to a respirator with controlled ventilation.
Echocardiographic data will be collected simultaneously with hemodynamic parameters - first at two control measurements, then after each of two different doses of the drug. Preload, afterload and heart rate will be kept stable during this intervention. The echocardiographic data is later analyzed offline for strain and strain rate.
To further investigate the dependency of strain and strain rate on changes in preload, afterload, and heart rate, these variables are consecutively changed prior to drug administration. For this purpose, all patients first have their baseline data recorded, thereafter are paced at two different rates, then preload and afterload is altered by passive leg elevation and phenylephrine, respectively. Hemodynamic and echocardiographic data are collected simultaneously at baseline and after each intervention. Before administration of the drugs, baseline conditions are restored.
- Being tested
- Levosimendan, Milrinone
- Keywords
- Transesophageal, Echocardiography, Milrinone, Levosimendan, Strain, Deformation, Diastole, Afterload, Preload, Systole
- Medical subject headings
- Heart Failure, Diastolic, Aortic Valve Stenosis, Sprains and Strains, Heart Murmurs, Systolic Murmurs
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Also called Daxim, Simdax
Data is collected at baseline as two controls.
Three physiological interventions follows, and data is collected after each:
Increasing heart rate in two steps by atrial pacing through a temporary pacemaker.
Raising cardiac preload by increasing central venous pressure through leg elevation.
Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine.
Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose.
MilrinoneDrug
Also called Primacor, Corotrop, Milicor
Data is collected at baseline as two controls.
Three physiological interventions follows, and data is collected after each:
Increasing heart rate in two steps by atrial pacing through a temporary pacemaker.
Raising cardiac preload by increasing central venous pressure through leg elevation.
Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine.
Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose.
| Study group | Role | What they receive |
|---|---|---|
| Levosimendan | Experimental | 1. st dose: 12 µg/kg iv bolus for 10 min followed by 0,1 µg/kg/min for 20 min.
2. nd dose: 12 µg/kg iv bolus for 10 min followed by 0,2 µg/kg/min for 20 min. Receives: Drug: Levosimendan |
| Milrinone | Experimental | 1. st dose: 48 µg/kg iv bolus for 10 min followed by 0,4 µg/kg/min for 20 min.
2. nd dose: 48 µg/kg iv bolus for 10 min followed by 0,8 µg/kg/min for 20 min. Receives: Drug: Milrinone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in diastolic strain rate
Diastolic strain rate defined as peak E wave strain rate as measured by 2D speckle tracking of the left ventricular wall.
Measured: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Secondary outcomes (2)
Change in systolic strain and strain rate
Systolic strain and strain rate defined as their respective peak values during systole, measured by 2D speckle tracking of the left ventricular wall.
Measured: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Change in cardiac output
Measured through pulmonary artery thermodilution as liters per minute. A baseline measurement is done before infusion is started.
Measured: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Apr 2015 (estimated)
- Study startMar 2014
- Primary completionMay 2016
- Study completionMay 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart Failure, DiastolicStudies of the same condition, open and under way.
- 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sahlgrenska University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Martin Fredholm, Sahlgrenska University Hospital
- Investigators
- Sven-Erik Ricksten, Professor, Principal investigator, Dept of Anesthesia and Intensive Care, University of Gothenburg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02408003
- Sponsor's protocol ID
- Fredholm strain study
- Status last verified
- May 2017
- First submitted
- 31 Mar 2015
- Last updated
- 9 May 2017
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 9 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- What Are the Changes in Cardiac Deformation Variables and Hemodynamic Parameters Following Changes in Cardiac Loading Conditions and After Administration of Two Different Inotropic Drugs.
- ClinicalTrials.gov ID
- NCT02408003
- Acronym / sponsor ID
- Fredholm strain study
- Keywords
- Transesophageal, Echocardiography, Milrinone, Levosimendan, Strain, Deformation, Diastole, Afterload
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Sahlgrenska University HospitalUniversity, hospital or other
- Study start
- Mar 2014 (actual)
- Primary completion
- May 2016 (actual)
- Study completion
- May 2017 (actual)
- First posted
- 3 Apr 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators want to compare the effects of two drugs, levosimendan and milrinone, on cardiac muscle, both in terms of contractility and relaxation. Half of the participants will be randomized to each drug. The effects will be measured through echocardiographic deformation analyses.
Since deformation analyses could be dependent on different loading conditions of the heart, a second purpose of the study is to investigate the changes on deformation parameters after applied changes in preload and afterload, but also heart rate.
Detailed description
Aortic stenosis is associated with myocardial hypertrophy and diastolic dysfunction. In patients undergoing open aortic valve replacement surgery due to stenosis, the investigators want to compare the effect on myocardial relaxation between two commonly used drugs, levosimendan and milrinone, using catheter-based measurements in combination with echocardiographic evaluation.
Standard anaesthesia and surgical care for these patients is performed. After surgery is completed and the participant is transferred to the intensive care unit, the studies are performed during general anaesthesia and the participants still connected to a respirator with controlled ventilation.
Echocardiographic data will be collected simultaneously with hemodynamic parameters - first at two control measurements, then after each of two different doses of the drug. Preload, afterload and heart rate will be kept stable during this intervention. The echocardiographic data is later analyzed offline for strain and strain rate.
To further investigate the dependency of strain and strain rate on changes in preload, afterload, and heart rate, these variables are consecutively changed prior to drug administration. For this purpose, all patients first have their baseline data recorded, thereafter are paced at two different rates, then preload and afterload is altered by passive leg elevation and phenylephrine, respectively. Hemodynamic and echocardiographic data are collected simultaneously at baseline and after each intervention. Before administration of the drugs, baseline conditions are restored.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levosimendan | Experimental | Drug: Levosimendan1. st dose: 12 µg/kg iv bolus for 10 min followed by 0,1 µg/kg/min for 20 min. 2. nd dose: 12 µg/kg iv bolus for 10 min followed by 0,2 µg/kg/min for 20 min. |
| Milrinone | Experimental | Drug: Milrinone1. st dose: 48 µg/kg iv bolus for 10 min followed by 0,4 µg/kg/min for 20 min. 2. nd dose: 48 µg/kg iv bolus for 10 min followed by 0,8 µg/kg/min for 20 min. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Subject has aortic valve stenosis
- Subject is scheduled for open heart aortic valve replacement with or without simultaneous coronary artery bypass grafting
Key exclusion criteria (4 listed)
- Less than normal systolic function, defined as ejection fraction less than 0,5
- Non-sinus rhythm
- Any major surgical complication
- Problems understanding the informed consent
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: Daxim, SimdaxData is collected at baseline as two controls. Three physiological interventions follows, and data is collected after each: Increasing heart rate in two steps by atrial pacing through a temporary pacemaker. Raising cardiac preload by increasing central venous pressure through leg elevation. Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine. Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose. | Drug | Levosimendan |
| MilrinoneAlso: Primacor, Corotrop, MilicorData is collected at baseline as two controls. Three physiological interventions follows, and data is collected after each: Increasing heart rate in two steps by atrial pacing through a temporary pacemaker. Raising cardiac preload by increasing central venous pressure through leg elevation. Raising cardiac afterload by increasing systemic vascular resistance through administering of phenylephrine. Baseline is restored, and data is collected before drug adminstration as two controls, then after a first (half) dose, and finally after a second (full) dose. | Drug | Milrinone |
Primary outcome
Change in diastolic strain rate
Time frame: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Diastolic strain rate defined as peak E wave strain rate as measured by 2D speckle tracking of the left ventricular wall.
2 secondary outcomes
Change in systolic strain and strain rate
Time frame: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Change in cardiac output
Time frame: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 May 2017.
- Individual participant dataSharing planned: No
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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.
Sven-Erik Ricksten, Professor principal investigator
Dept of Anesthesia and Intensive Care, University of Gothenburg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Levosimendan and Milrinone in people with Heart Failure, Diastolic and Aortic Valve Stenosis, run by Sahlgrenska University Hospital at 1 site in Sweden.
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 2 inclusion and 4 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 9 May 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in 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.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Change in diastolic strain rate (time frame: After each physiologic intervention, and at 30 and 60 min after start of iv infusion of drug.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 9 May 2017.