Cardiogenic ShockNCT04917497
Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock
An observational study of Cardiogenic Shock and Cardiorenal Syndrome, run by University of Zurich.
Trial summary
To determine whether Levosimendan infusion in patients with cardiogenic shock and cardiorenal syndrome refractory to standard inotropic therapy, improves hemodynamics and renal function, whilst being safe. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiogenic Shock, Cardiorenal Syndrome, Acute Kidney Failure
- What is being tested?
- Levosimendan
- Type of treatment
- Injection or infusion
- How many people
- 43 participants
- Where
- No sites listed yet
- Study dates
- 30 Jun 2011to 30 Apr 2014
- Phase
- Observational
- 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
Study population: All patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan
Who may be able to join
- Levosimendan
- Cardiogenic Shock
- Continuous monitoring of cardiac output at the start of and during treatment with Levosimendan
Who cannot join
- Extracorporal hemodynamic support or an implanted ventricular assist device
- Previous therapy with Levosimendan during the index hospitalization
- Refusal of participation in the study
About this study
To determine whether Levosimendan infusion in patients with cardiogenic shock and cardiorenal syndrome refractory to standard inotropic therapy, improves hemodynamics and renal function, whilst being safe.
Read the detailed description
Cardiogenic Shock or the state of systemic hypoxia albeit initially preserved intra-vascular volume and intact vascular function, is solely the result of insufficient cardiac output [1-2]. The ensuing centralization and redistribution of blood-volume, is induced by a stimulation of the renin-angiotensin system, as well as vasopressin and endogenous catecholamine liberation [2-3]. Precipitating Cardiogenic Shock has a direct effect on the kidney, also called the cardiorenal syndrome [4].
The overall consensus for the therapy of cardiogenic shock is the use of inotropes to increase cardiac output and reverse organ hypoxia [2], nevertheless their increase of myocardial and glomerular oxygen consumption make them a double edged sword to use in cardiogenic shock and more prominently in cardiogenic shock coupled with pronounced cardiorenal syndrome.
Levosimendan is an inotropic agent that was developed for the treatment of severely decompensated heart failure. It exerts its inotropic effects primarily through sensitizing Troponin C to calcium and thereby increasing contraction of cardiac myofilaments during systole [5]. Unlike other inotropic agents, Levosimendan acts independently of the beta adrenergic receptor [5]. Additionally, the effect of Levosimendan could be beneficial for the kidneys function by decreasing pre-glomerular arteriolar vasotonus whilst keeping post-glomerular arteriolar vasotonus constant [6].
In light of the scarce but promising literature the question arises if Levosimendan can safely ameliorate cardiac and renal function concomitantly in patients presenting the combination of cardiogenic shock and cardiorenal syndrome.
- Being tested
- Levosimendan
- Keywords
- Levosimendan, Inotropic Agent
- Medical subject headings
- Shock, Cardiogenic, Cardio-Renal Syndrome, Acute Kidney Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Levosimendan was administered according to a standardized treatment protocol. A total dose of 12.5mg or 25mg (corresponding to one or two ampoules) was given at an infusion rate of 0.05 μg/kg/min to 0.2μg/kg/min with or without a loading dose (6 μg/kg or 3 μg/kg over 10 minutes). The decision about total dose, infusion rate and loading dose was at the discretion of the treating physician.
| Study group | Role | What they receive |
|---|---|---|
| Levosimendan Treated Group | All patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan. Receives: Drug: Levosimendan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Cardiac Index
Temporal development of Cardiac Index post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Change in Cardiac Preload Pressures
Temporal development of Wedge Pressure/ Central Venous Pressure post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Change in Mean Arterial Pressure
Temporal development of Mean Arterial Pressure post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Change in Vasoactive/ Inotropic Dosage
Temporal development of Norepinephrine/ Dobuatmine Dosage post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Change in Renal Function
Temporal development of eGFR (Creatinin estimated) post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Change in Fluid Balance
Temporal development of Fluid Balance post Levosimendan Infusion up until 120 hours
Measured: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Jun 2021
- Study start30 Jun 2011
- Primary completion30 Apr 2014
- Study completion30 Apr 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for Cardiogenic ShockStudies of the same condition, open and under way.
- More trials run by University of ZurichThe 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 43 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Zurich
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Marco Maggiorini, Principal investigator, Medizinische Intensivstation D-HOER 27, UniversitatsSpital Zürich
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04917497
- Sponsor's protocol ID
- Levosimendan
- Status last verified
- Jun 2021
- First submitted
- 31 May 2021
- Last updated
- 8 Jun 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Califf RM, Bengtson JR. Cardiogenic shock. N Engl J Med. 1994 Jun 16;330(24):1724-30. doi: 10.1056/NEJM199406163302406. No abstract available.
PubMed 8190135van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17;136(16):e232-e268. doi: 10.1161/CIR.0000000000000525. Epub 2017 Sep 18.
PubMed 28923988Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation. 2003 Jun 24;107(24):2998-3002. doi: 10.1161/01.CIR.0000075927.67673.F2. No abstract available.
PubMed 12821585Ronco C, House AA, Haapio M. Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med. 2008 May;34(5):957-62. doi: 10.1007/s00134-008-1017-8. Epub 2008 Feb 5.
PubMed 18251008Papp Z, Edes I, Fruhwald S, De Hert SG, Salmenpera M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikstrom BG, Jorgensen K, Filippatos G, Parissis JT, Gonzalez MJ, Parkhomenko A, Yilmaz MB, Kivikko M, Pollesello P, Follath F. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7. doi: 10.1016/j.ijcard.2011.07.022. Epub 2011 Jul 23.
PubMed 21784540Bragadottir G, Redfors B, Ricksten SE. Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit Care Med. 2013 Oct;41(10):2328-35. doi: 10.1097/CCM.0b013e31828e946a.
PubMed 23921271
Study at a glance
From the registry record, last updated by the sponsor on 8 Jun 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levosimendan Infusion in Critically Ill Patients With Cardiogenic Shock
- ClinicalTrials.gov ID
- NCT04917497
- Acronym / sponsor ID
- Levosimendan
- Keywords
- Levosimendan, Inotropic Agent
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 43 participants (actual)
- Lead sponsor
- University of ZurichUniversity, hospital or other
- Study start
- 30 Jun 2011 (actual)
- Primary completion
- 30 Apr 2014 (actual)
- Study completion
- 30 Apr 2014 (actual)
- First posted
- 8 Jun 2021 (actual)
- 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.
To determine whether Levosimendan infusion in patients with cardiogenic shock and cardiorenal syndrome refractory to standard inotropic therapy, improves hemodynamics and renal function, whilst being safe.
Detailed description
Cardiogenic Shock or the state of systemic hypoxia albeit initially preserved intra-vascular volume and intact vascular function, is solely the result of insufficient cardiac output [1-2]. The ensuing centralization and redistribution of blood-volume, is induced by a stimulation of the renin-angiotensin system, as well as vasopressin and endogenous catecholamine liberation [2-3]. Precipitating Cardiogenic Shock has a direct effect on the kidney, also called the cardiorenal syndrome [4].
The overall consensus for the therapy of cardiogenic shock is the use of inotropes to increase cardiac output and reverse organ hypoxia [2], nevertheless their increase of myocardial and glomerular oxygen consumption make them a double edged sword to use in cardiogenic shock and more prominently in cardiogenic shock coupled with pronounced cardiorenal syndrome.
Levosimendan is an inotropic agent that was developed for the treatment of severely decompensated heart failure. It exerts its inotropic effects primarily through sensitizing Troponin C to calcium and thereby increasing contraction of cardiac myofilaments during systole [5]. Unlike other inotropic agents, Levosimendan acts independently of the beta adrenergic receptor [5]. Additionally, the effect of Levosimendan could be beneficial for the kidneys function by decreasing pre-glomerular arteriolar vasotonus whilst keeping post-glomerular arteriolar vasotonus constant [6].
In light of the scarce but promising literature the question arises if Levosimendan can safely ameliorate cardiac and renal function concomitantly in patients presenting the combination of cardiogenic shock and cardiorenal syndrome.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Levosimendan Treated Group | – | Drug: LevosimendanAll patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients consecutively admitted to the medical ICU of the University Hospital Zurich aged over 18 years, with an underlying cardiogenic shock, receiving Levosimendan
Key inclusion criteria (3 listed)
- Levosimendan
- Cardiogenic Shock
- Continuous monitoring of cardiac output at the start of and during treatment with Levosimendan
Key exclusion criteria (3 listed)
- Extracorporal hemodynamic support or an implanted ventricular assist device
- Previous therapy with Levosimendan during the index hospitalization
- Refusal of participation in the study
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 |
|---|---|---|
| LevosimendanLevosimendan was administered according to a standardized treatment protocol. A total dose of 12.5mg or 25mg (corresponding to one or two ampoules) was given at an infusion rate of 0.05 μg/kg/min to 0.2μg/kg/min with or without a loading dose (6 μg/kg or 3 μg/kg over 10 minutes). The decision about total dose, infusion rate and loading dose was at the discretion of the treating physician. | Drug | Levosimendan Treated Group |
Primary outcome
Change in Cardiac Index
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of Cardiac Index post Levosimendan Infusion up until 120 hours
Change in Cardiac Preload Pressures
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of Wedge Pressure/ Central Venous Pressure post Levosimendan Infusion up until 120 hours
Change in Mean Arterial Pressure
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of Mean Arterial Pressure post Levosimendan Infusion up until 120 hours
Change in Vasoactive/ Inotropic Dosage
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of Norepinephrine/ Dobuatmine Dosage post Levosimendan Infusion up until 120 hours
Change in Renal Function
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of eGFR (Creatinin estimated) post Levosimendan Infusion up until 120 hours
Change in Fluid Balance
Time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion
Temporal development of Fluid Balance post Levosimendan Infusion up until 120 hours
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 8 Jun 2021.
- Background: PubMed 8190135Califf RM, Bengtson JR. Cardiogenic shock. N Engl J Med. 1994 Jun 16;330(24):1724-30. doi: 10.1056/NEJM199406163302406. No abstract available.
- Background: PubMed 28923988van Diepen S, Katz JN, Albert NM, Henry TD, Jacobs AK, Kapur NK, Kilic A, Menon V, Ohman EM, Sweitzer NK, Thiele H, Washam JB, Cohen MG; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; and Mission: Lifeline. Contemporary Management of Cardiogenic Shock: A Scientific Statement From the American Heart Association. Circulation. 2017 Oct 17;136(16):e232-e268. doi: 10.1161/CIR.0000000000000525. Epub 2017 Sep 18.
- Background: PubMed 12821585Hochman JS. Cardiogenic shock complicating acute myocardial infarction: expanding the paradigm. Circulation. 2003 Jun 24;107(24):2998-3002. doi: 10.1161/01.CIR.0000075927.67673.F2. No abstract available.
- Background: PubMed 18251008Ronco C, House AA, Haapio M. Cardiorenal syndrome: refining the definition of a complex symbiosis gone wrong. Intensive Care Med. 2008 May;34(5):957-62. doi: 10.1007/s00134-008-1017-8. Epub 2008 Feb 5.
- Background: PubMed 21784540Papp Z, Edes I, Fruhwald S, De Hert SG, Salmenpera M, Leppikangas H, Mebazaa A, Landoni G, Grossini E, Caimmi P, Morelli A, Guarracino F, Schwinger RH, Meyer S, Algotsson L, Wikstrom BG, Jorgensen K, Filippatos G, Parissis JT, Gonzalez MJ, Parkhomenko A, Yilmaz MB, Kivikko M, Pollesello P, Follath F. Levosimendan: molecular mechanisms and clinical implications: consensus of experts on the mechanisms of action of levosimendan. Int J Cardiol. 2012 Aug 23;159(2):82-7. doi: 10.1016/j.ijcard.2011.07.022. Epub 2011 Jul 23.
- Background: PubMed 23921271Bragadottir G, Redfors B, Ricksten SE. Effects of levosimendan on glomerular filtration rate, renal blood flow, and renal oxygenation after cardiac surgery with cardiopulmonary bypass: a randomized placebo-controlled study. Crit Care Med. 2013 Oct;41(10):2328-35. doi: 10.1097/CCM.0b013e31828e946a.
- 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.
Marco Maggiorini principal investigator
Medizinische Intensivstation D-HOER 27, UniversitatsSpital Zürich
Questions about this trial
What is this clinical trial studying?
An observational study of Cardiogenic Shock and Cardiorenal Syndrome, run by University of Zurich.
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 3 inclusion and 3 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 8 Jun 2021. Status can change between updates, so confirm with the study contact before making plans.
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 Cardiac Index (time frame: Mixed Model Assessment at 0, 1, 2, 4, 6, 12, 24, 48, 72, 96 and 120 hours post Levosimendan Infusion). The study lists 6 primary outcomes in all. 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 NCT04917497, which also lists 6 linked publications.
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 8 Jun 2021.