Hypertension, Pulmonarylevos-milrNCT04718350

Treatment of Pulmonary Hypertension in High-risk Cardiac Surgery Patients Using Inhalational and Intravenous Agents

A study testing levosimendan at a dose of 6 mcg/kg and milrinone at a dose of 50 mcg/kg in people with Hypertension, Pulmonary and Cardiac Failure, run by Aretaieion University Hospital at 1 site in Greece.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The aim of this study is to examine and compare the effect of Levosimendan and Milrinone administered intravenously and via inhalation respectively in cardiac surgery patients with pulmonary hypertension and right ventricular dysfunction. Read more about this study

Who is it for?: Ages 18 to 75 years
Conditions the study is for: Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality
What is being tested?: levosimendan at a dose of 6 mcg/kg and milrinone at a dose of 50 mcg/kg
Type of treatment: Injection or infusion
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 40 participants
Where: 1 siteGreece
Study dates: 27 Jan 2021to 30 Dec 2023
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 to 75 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively
elective cardiac surgery

Who cannot join

primary pulmonary hypertension
thromboembolic disease
chronic obstructive pulmonary disease
emergency surgery
redo surgery
inability to consent to the study

Trial locations and contacts

1 site in 1 country.

Greece1 site

Onassis Cardiac Surgery Center
Athens, 17674

Other trials in Greece

About this study

Official title: Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension

Read the detailed description

Pulmonary hypertension (PH) is a pathophysiological disorder hemodynamically characterized by increased pulmonary vascular resistance and pressure. This can lead to right ventricle pressure overload and failure, which is worsened by cardiopulmonary bypass (CPB) and extracorporeal circulation and is accompanied by high rates of morbidity and mortality in cardiac surgery patients. Pharmacological agents used to decrease pulmonary vascular resistance and right ventricle afterload are prostaglandins, iloprost, milrinone, nitric oxide (NO) and recently Levosimendan. These agents can be administered intravenously or via inhalation.

In this study, the intravenous administration of Levosimendan will be compared with the inhalational use of milrinone in patients with pulmonary hypertension undergoing cardiac surgery.

In this setting, 40 patients with PH caused by left sided heart disease, will be assigned into two groups:

GROUP A: Intravenous administration of Levosimendan in dosage 6mcg/kg after induction of anesthesia.

GROUP B: Inhalational administration of milrinone in dosage 50mcg/kg after induction of anesthesia.

Before and after the administration of the drug, heart function will be evaluated by hemodynamic measurements obtained by the Swan-Ganz catheter. These parameters will be heart rate (HR), blood pressure (BP), mean pulmonary arterial pressure (MPAP), central venous pressure (CVP), cardiac output (CO), pulmonary capillary wedge pressure (PCWP), cardiac index (CI), systemic vascular resistance (SVR), pulmonary vascular resistance (PVR). Transthoracic echocardiography (TTE) and transoesophageal echocardiography (TOE) will also be used.

This study will lead to conclusions regarding the effectiveness of intravenous administration of Levosimendan and inhalational use of Milrinone in the treatment of right heart failure and PH in cardiac surgery patients.

Conditions: Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality
Being tested: levosimendan at a dose of 6 mcg/kg, milrinone at a dose of 50 mcg/kg
Keywords: pulmonary vascular resistance, pulmonary hypertension, vasodilators, milrinone, levosimendan, cardiopulmonary bypass
Medical subject headings: Hypertension, Pulmonary, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

levosimendan at a dose of 6 mcg/kgDrug
Also called Group Levo
levosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction
milrinone at a dose of 50 mcg/kgDrug
Also called Group Milri
milrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction

Study groups in NCT04718350
Study group	Role	What they receive
Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia	Active comparator	in this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass Receives: Drug: levosimendan at a dose of 6 mcg/kg
Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia	Active comparator	in this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass Receives: Drug: milrinone at a dose of 50 mcg/kg

What is being measured

The primary outcome is the main question the study is designed to answer.

change from baseline in mean pulmonary arterial pressure (MPAP)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in pulmonary vascular resistance (PVR)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in mean arterial pressure (MAP)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in systemic vascular resistance (SVR)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in pulmonary capillary wedge pressure (PCWP)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in cardiac output (CO)
a Swan-Ganz catheter will be used for hemodynamic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in tricuspid annular plane systolic excursion (TAPSE)
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
change from baseline in fractional area change
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
Measured: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
length of ICU stay
duration of patient stay in ICU in days
Measured: postoperatively, an average period of 7-10 days
hospitalization time
duration of hospital stay after surgery in days
Measured: postoperatively, up to 20 days after the operation

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

27 Jan 202130 Dec 2023

First posted22 Jan 2021
Study start27 Jan 2021
Primary completion30 Dec 2023
Study completion30 Dec 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Hypertension, PulmonaryStudies 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: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 40 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT04718350
Sponsor's protocol ID: levo-milri
Acronym: levos-milr
Status last verified: Jul 2025
First submitted: 16 Jan 2021
Last updated: 22 Jul 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Theodoraki K, Thanopoulos A, Rellia P, Leontiadis E, Zarkalis D, Perreas K, Antoniou T. A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension. Heart Vessels. 2017 Dec;32(12):1488-1497. doi: 10.1007/s00380-017-1023-2. Epub 2017 Jul 17.
PubMed 28717881
Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb;108(2):422-33. doi: 10.1213/ane.0b013e31818d8b92.
PubMed 19151265
Hansen MS, Andersen A, Nielsen-Kudsk JE. Levosimendan in pulmonary hypertension and right heart failure. Pulm Circ. 2018 Jul-Sep;8(3):2045894018790905. doi: 10.1177/2045894018790905. Epub 2018 Jul 6.
PubMed 29979110
Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth. 2018 Jul-Sep;21(3):328-332. doi: 10.4103/aca.ACA_19_18.
PubMed 30052230
Elhassan A, Essandoh M. Inhaled Levosimendan for Pulmonary Hypertension Treatment During Cardiac Surgery: A Novel Application to Avoid Systemic Hypotension. J Cardiothorac Vasc Anesth. 2019 Apr;33(4):1169-1170. doi: 10.1053/j.jvca.2018.11.039. Epub 2018 Nov 28. No abstract available.
PubMed 30612930

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease
Active, not recruitingPhase 1
A Pilot Study of Microbiota Transplant With Antibiotic Preconditioning and Fiber Supplementation in Pulmonary Arterial Hypertension (GUT RESTORE-PAH)
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RecruitingObservational study
Natural History Study of Biomarkers in Pulmonary Arterial Hypertension
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Active, not recruitingPhase 1
Study of Intravenous ZMA001 in Healthy Subjects
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All Hypertension, Pulmonary trials

Study at a glance

From the registry record, last updated by the sponsor on 22 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Comparison of Intravenous Levosimendan and Inhalational Milrinone in High Risk Cardiac Patients With Pulmonary Hypertension
ClinicalTrials.gov ID: NCT04718350
Acronym / sponsor ID: levos-milr / levo-milri
Conditions: Hypertension, Pulmonary, Cardiac Failure, Pulmonary Vascular Resistance Abnormality
Keywords: pulmonary vascular resistance, pulmonary hypertension, vasodilators, milrinone, levosimendan, cardiopulmonary bypass
Study type: Interventional
Recruitment status: Completed
Enrolment: 40 participants (actual)
Lead sponsor: Aretaieion University HospitalUniversity, hospital or other
Study start: 27 Jan 2021 (actual)
Primary completion: 30 Dec 2023 (actual)
Study completion: 30 Dec 2023 (actual)
First posted: 22 Jan 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.

Detailed description

In this study, the intravenous administration of Levosimendan will be compared with the inhalational use of milrinone in patients with pulmonary hypertension undergoing cardiac surgery.

In this setting, 40 patients with PH caused by left sided heart disease, will be assigned into two groups:

GROUP A: Intravenous administration of Levosimendan in dosage 6mcg/kg after induction of anesthesia.

GROUP B: Inhalational administration of milrinone in dosage 50mcg/kg after induction of anesthesia.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia	Active comparator	Drug: levosimendan at a dose of 6 mcg/kgin this group, 6 mcg/kg of levosimendan will be administered intravenously after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass
Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia	Active comparator	Drug: milrinone at a dose of 50 mcg/kgin this group, 50 mcg/kg of milrinone will be administered via inhalation after anesthesia induction, aiming at prevention of pulmonary hypertension post bypass

Who may qualify

Ages: 18 to 75 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (2 listed)

patients with pulmonary hypertension due to left ventricular dysfunction based on echocardiographic diagnosis preoperatively
elective cardiac surgery

Key exclusion criteria (6 listed)

primary pulmonary hypertension
thromboembolic disease
chronic obstructive pulmonary disease
emergency surgery
redo surgery

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
levosimendan at a dose of 6 mcg/kgAlso: Group Levolevosimendan will be administered intravenously at a dose of 6 mcg/kg after anesthesia induction	Drug	Intravenous administration of Levosimendan at a dosage of 6 mcg/kg after induction of anesthesia
milrinone at a dose of 50 mcg/kgAlso: Group Milrimilrinone will be administered via inhalation at a dose of 50 mcg/kg after anesthesia induction	Drug	Inhalational administration of Milrinone at a dosage of 50 mcg/kg after induction of anesthesia

Primary outcome

change from baseline in mean pulmonary arterial pressure (MPAP)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary vascular resistance (PVR)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in mean arterial pressure (MAP)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in systemic vascular resistance (SVR)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in pulmonary capillary wedge pressure (PCWP)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in cardiac output (CO)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
a Swan-Ganz catheter will be used for hemodynamic measurements
change from baseline in tricuspid annular plane systolic excursion (TAPSE)
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
change from baseline in fractional area change
Time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission
transthoracic and transesophageal echocardiography will be used for echocardiographic measurements
length of ICU stay
Time frame: postoperatively, an average period of 7-10 days
duration of patient stay in ICU in days
hospitalization time
Time frame: postoperatively, up to 20 days after the operation
duration of hospital stay after surgery in days

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 22 Jul 2025.
Background: PubMed 28717881Theodoraki K, Thanopoulos A, Rellia P, Leontiadis E, Zarkalis D, Perreas K, Antoniou T. A retrospective comparison of inhaled milrinone and iloprost in post-bypass pulmonary hypertension. Heart Vessels. 2017 Dec;32(12):1488-1497. doi: 10.1007/s00380-017-1023-2. Epub 2017 Jul 17.
Background: PubMed 19151265Haddad F, Couture P, Tousignant C, Denault AY. The right ventricle in cardiac surgery, a perioperative perspective: II. Pathophysiology, clinical importance, and management. Anesth Analg. 2009 Feb;108(2):422-33. doi: 10.1213/ane.0b013e31818d8b92.
Background: PubMed 29979110Hansen MS, Andersen A, Nielsen-Kudsk JE. Levosimendan in pulmonary hypertension and right heart failure. Pulm Circ. 2018 Jul-Sep;8(3):2045894018790905. doi: 10.1177/2045894018790905. Epub 2018 Jul 6.
Background: PubMed 30052230Kundra TS, Nagaraja PS, Bharathi KS, Kaur P, Manjunatha N. Inhaled levosimendan versus intravenous levosimendan in patients with pulmonary hypertension undergoing mitral valve replacement. Ann Card Anaesth. 2018 Jul-Sep;21(3):328-332. doi: 10.4103/aca.ACA_19_18.
Background: PubMed 30612930Elhassan A, Essandoh M. Inhaled Levosimendan for Pulmonary Hypertension Treatment During Cardiac Surgery: A Novel Application to Avoid Systemic Hypotension. J Cardiothorac Vasc Anesth. 2019 Apr;33(4):1169-1170. doi: 10.1053/j.jvca.2018.11.039. Epub 2018 Nov 28. No abstract available.
Individual participant dataSharing planned: No

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An Open-Label Extension Study to Evaluate Inhaled Treprostinil SMI in Participants With Pulmonary Hypertension Associated With Chronic Obstructive Pulmonary Disease (PH-COPD)
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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.

Kassiani Theodoraki, PhD, DESA principal investigator

Aretaieion University Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

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 6 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 22 Jul 2025. 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 Greece. 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 from baseline in mean pulmonary arterial pressure (MPAP) (time frame: 20 minutes after vasodilator administration, at the end of surgery and 2 hours after Intensive Care Unit (ICU) admission). The study lists 10 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 NCT04718350, which also lists 5 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 22 Jul 2025.