An interventional study of Infusion of levosimendan and Placebo infusion "Soluvit" in LEVOSIMENDAN, PULMONARY THROMBOENDARTERECTOMY and Chronic Thromboembolic Pulmonary Hypertension (CTEPH), sponsored by Meshalkin Research Institute of Pathology of Circulation. Recruiting at 1 site in Russia. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-04.
Sponsored by Meshalkin Research Institute of Pathology of Circulation · Not applicable, Interventional, and Treatment
A single-center pilot prospective randomized placebo-controlled double-blind clinical trial.
Study objective - to investigate the efficacy and safety of levosimendan in patients in the perioperative period following pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension (CTEPH).
Research Objectives:
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare and severe form of pulmonary hypertension resulting from thrombotic obstruction of the pulmonary arteries. It is typically a late complication of acute pulmonary embolism. The incidence of CTEPH has been reported to reach 13 cases per million population per year.
Organized thrombotic masses cause stenosis or obstruction of the pulmonary arteries, leading to increased pulmonary artery pressure and pulmonary vascular resistance. This results in redistribution of pulmonary blood flow, microangiopathy, and remodeling of small-caliber pulmonary vessels. Pulmonary endarterectomy (PEA) is the recommended standard of care for patients with CTEPH and can be curative. In experienced centers, mortality rates are less than 5%.
Residual pulmonary hypertension after PEA, defined as a mean pulmonary artery pressure ≥25 mmHg, occurs in 17-51% of patients. This complication is associated with residual thrombotic material in distal pulmonary arteries and small-vessel disease. Severe pulmonary hypertension causes right ventricular maladaptive remodeling and dysfunction, ultimately leading to right ventricular failure, which is the most important determinant of survival and quality of life. Residual pulmonary hypertension negatively affects long-term survival, with higher mortality associated with mean pulmonary artery pressure ≥36 mmHg and pulmonary vascular resistance ≥416 dyn·s·cm-⁵.
Currently, a multimodal approach to CTEPH is being considered. Surgery addresses the primary component by removing thrombotic masses, but pharmacotherapy is required for the microvascular component and persistently elevated pulmonary artery pressure. Targeted therapies are costly, and their benefit remains unclear. Clinical guidelines currently recommend only symptomatic therapy for patients with residual pulmonary hypertension and right ventricular failure after PEA, and no optimal treatment strategy has been defined for this complication in the early postoperative period.
Rationale for Levosimendan: Levosimendan has shown promising effects in pulmonary hypertension and right ventricular failure. Its mechanism of action involves opening ATP-dependent potassium channels in vascular smooth muscle cells, leading to vasodilation and reduction of both preload and afterload. Additionally, levosimendan binds to cardiac troponin C, increasing myofibril contractility. Previous studies have demonstrated that levosimendan reduces pulmonary artery pressure and pulmonary vascular resistance, improves right ventricular function (including increased TAPSE, ejection fraction, and cardiac output), and suppresses smooth muscle cell proliferation in pulmonary arteries. However, no studies to date have investigated the effect of levosimendan in patients with CTEPH undergoing pulmonary endarterectomy, and the drug has not previously been used in the perioperative management of this patient population.
Study objective is to evaluate the effect of levosimendan on pulmonary artery pressure and right ventricular function in patients undergoing pulmonary endarterectomy for CTEPH.
1,092 studies on the registry are indexed under Hypertension, Pulmonary; 244 are open to participants now.
This study's planned enrollment of 50 is above the median of 35 across 649 interventional studies indexed under Hypertension, Pulmonary.
Browse Hypertension, Pulmonary studies →Meshalkin Research Institute of Pathology of Circulation is the lead sponsor of 119 studies on the registry; 9 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria :
Discontinuation Criteria (or Withdrawal Criteria):
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Creatinine clearance (CrCl)
How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Child-Pugh class
A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
A levosimendan infusion after induction of anesthesia.
Drug: Infusion of levosimendan
A placebo infusion after induction of anesthesia.
Drug: Placebo infusion "Soluvit"
Infusion of levosimendan will be initiated after the induction of anesthesia, discontinued at the onset of patient cooling, and resumed at the time of rewarming at 34°C. The drug will be administered using an infusion pump as a continuous infusion at a rate of 0.1 mcg/kg/min. The duration of the drug infusion will be up to 48 hours. Preoperative management will be conducted according to the patients' primary and concomitant diseases.
Patients in the placebo group will receive an equivalent amount of a colored solution of Soluvit.Soluvit (ATC B05XC; a yellow vitamin mixture indistinguishable from the investigational drug, levosimendan). Preoperative management will be conducted according to the patients' primary and concomitant diseases.
Mean pulmonary artery pressure (mPAP)
Mean pulmonary artery pressure (mPAP) measured 24 hours after the end of surgery
Time frame: 24 hours at the end of surgery
Pulmonary Vascular Resistance (PVR)
Pulmonary vascular resistance
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Pulmonary Artery Pulsatility Index (PAPI)
Pulmonary artery pulsatility index. PAPi = (PASP - PADP) / RAP (PASP - PADP): Pulmonary Artery Pulse Pressure. This is the difference between the pressure in the pulmonary artery when the heart contracts (systolic) and relaxes (diastolic). RAP: Right Atrial Pressure.
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Pulmonary Artery Pressure (PAP)
Pulmonary artery pressure
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Arterial Blood Pressure (ABP)
Arterial blood pressure
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Central Venous Pressure (CVP)
Central venous pressure
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Cardiac Index (CI)
Cardiac index
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Systemic Vascular Resistance (SVR)
Systemic vascular resistance
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Right Ventricular Stroke Work Index (RVSWI)
Right ventricular stroke work index
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Pulmonary Capillary Wedge Pressure (PAWP)
Pulmonary capillary wedge pressure
Time frame: • before skin incision • at the end of surgery • 4 hours after of surgery • 24 hours after of surgery • 48 hours after of surgery • 72 hours after of surgery
Ejection fraction
Ejection fraction (EF) of both the right and left ventricles (LVEF and RVEF)
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Right Ventricular End-Diastolic Volume (RVEDV)
Right ventricular end diastolic volume
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Right Ventricular systolic pressure (RVSP)
Right ventricular systolic pressure
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Fractional area change (FAC) of the right ventricle
Fractional area change (FAC) of the right ventricle
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Tricuspid annular plane systolic excursion (TAPSE)
Tricuspid annular plane systolic excursion
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Right ventricular free-wall longitudinal strain (RV FW LS)
Right ventricular free-wall longitudinal strain
Time frame: • before skin incision • at the end of surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Quantitative troponin I level
Quantitative concentration of troponin I
Time frame: • before skin incision• 24 hours after the end of surgery• 48 hours after surgery
Vasoactive Inotropic Support
In the perioperative period, the Vasoactive-Inotropic Score (VIS) will be calculated using the following formula: VIS = dobutamine (mcg/kg/min) + dopamine (mcg/kg/min) + (100 × epinephrine (mcg/kg/min) + (100 × norepinephrine (mcg/kg/min)) + (10 × milrinone (mcg/kg/min))
Time frame: • before skin incision • at the end of surgery • 4 hours after surgery • 24 hours after surgery • 48 hours after surgery • 72 hours after surgery
Residual Pulmonary Hypertension
Number of participants with residual pulmonary hypertension, defined as postoperative mean pulmonary artery pressure (mPAP) \> 25 mm Hg, measured by right heart catheterization in the postoperative period (up to 72 hours after surgery).
Time frame: From the end of surgery up to 72 hours postoperatively
Incidence of reperfusion pulmonary edema
Number of participants who develop pulmonary edema within 24 hours following pulmonary endarterectomy (PEA), confirmed by chest X-ray or chest CT and clinical criteria (including dyspnea, hypoxemia, and bilateral infiltrates), characterized by the presence of frothy secretions in the endotracheal tube (ETT), asymmetric opacities on chest X-ray, and an oxygenation index (PaO₂/FiO₂) \< 300 mm Hg in the early postoperative period (up to 72 hours)
Time frame: From the end of surgery up to 72 hours postoperatively
Incidence of cardiac arrhythmias
Proportion of participants who develop any new-onset cardiac arrhythmia (including atrial fibrillation/flutter, ventricular tachycardia) during the study period, as documented by 12-lead ECG or continuous cardiac monitoring.
Time frame: 30 days
Cardiovascular events: myocardial infarction or stroke
Number of participants with cardiovascular events, defined as myocardial infarction (MI) or stroke (cerebrovascular accident, CVA), occurring during the postoperative period.Myocardial infarction is defined according to the Fourth Universal Definition of Myocardial Infarction (elevated cardiac troponin with at least one of the following: ischemic symptoms, new ischemic ECG changes, or imaging evidence of new loss of viable myocardium). Stroke is defined as an acute episode of focal or global neurological dysfunction caused by infarction or hemorrhage in the brain, spinal cord, or retina, confirmed by neuroimaging (CT or MRI).
Time frame: 30 days
Respiratory Complications: Pneumothorax
Number of participants with postoperative pneumothorax, defined as the presence of air in the pleural cavity, confirmed by chest X-ray or chest CT, occurring during the postoperative period.
Time frame: 30 days
Neurological Complications: Seizures
Number of participants with postoperative seizures, defined as a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Diagnosis is based on clinical assessment and, when available, confirmed by electroencephalography (EEG).
Time frame: From enrollment to the end of treatment at 30 days
Renal complications: acute kidney injury (AKI) according to KDIGO criteria
Number of participants with postoperative acute kidney injury (AKI), defined and staged according to the Kidney Disease: Improving Global Outcomes (KDIGO) criteria, occurring during the early postoperative period (up to 48 hours after surgery). AKI is defined as any of the following: increase in serum creatinine by ≥ 0.3 mg/dL (≥ 26.5 μmol/L) within 48 hours; or increase in serum creatinine to ≥ 1.5 times baseline, which is known or presumed to have occurred within the prior 7 days; or urine output \< 0.5 mL/kg/hour for 6 hours. AKI is staged as follows: Stage 1 (serum creatinine 1.5-1.9 times baseline or ≥ 0.3 mg/dL increase, or urine output \< 0.5 mL/kg/hour for 6-12 hours), Stage 2 (serum creatinine 2.0-2.9 times baseline, or urine output \< 0.5 mL/kg/hour for ≥ 12 hours), and Stage 3 (serum creatinine ≥ 3.0 times baseline, or increase to ≥ 4.0 mg/dL, or initiation of renal replacement therapy, or urine output \< 0.3 mL/kg/hour for ≥ 24 hours, or anuria for ≥ 12 hours).
Time frame: 30 days
Renal replacement therapy (RRT)
Number of participants who require renal replacement therapy (RRT) in the early postoperative period
Time frame: From enrollment to the end of treatment at 30 days
Use of inhaled nitric oxide (NO) and/or iloprost
Number of participants requiring administration of inhaled nitric oxide (NO) and/or inhaled iloprost in the postoperative period. for the management of residual pulmonary hypertension or right ventricular dysfunction. This includes administration as monotherapy or in combination
Time frame: 30 days
Blood transfusion
Number of participants requiring perioperative blood transfusion, including packed red blood cells (PRBCs), fresh frozen plasma (FFP), platelet concentrates, or cryoprecipitate, in the postoperative period. Transfusion requirements will be recorded as the number of participants receiving any transfusion.
Time frame: 30 days
Inotropic/vasopressor support
Number of participants requiring postoperative inotropic and/or vasopressor support in the early postoperative period
Time frame: From the end of surgery up to 72 hours postoperatively
Duration of mechanical ventilation (MV)
Total duration of invasive mechanical ventilation (MV) measured in hours (or days) from the time of intubation in the operating room or ICU until successful extubation. This includes the total time on the ventilator, both in the operating room and in the ICU, and includes any episodes of reintubation.
Time frame: 30 days
Duration of ICU stay
Total length of stay in the intensive care unit (ICU) measured in days from the time of admission to the ICU after surgery until discharge from the ICU to the general ward.
Time frame: 90 days
Duration of hospital stay
Total length of hospital stay measured in days
Time frame: 90 days
In-hospital mortality
yes/no
Time frame: 90 days
Plan to share: No — Data sharing is not planned as this is a single-center study and institutional regulations do not permit sharing of individual patient data.
Started Apr 2025 (actual). Primary completion is estimated for Nov 2027, 31 months after the start.
Of 134 non-industry interventional studies with no phase under Hypertension, Pulmonary, half reached primary completion within 20 months of starting (the median), counting those still running; a quarter within 9 and three quarters within 46. This study's planned 31 months is above that.
Counting every sponsor, half of 148 studies reached it within 23 months; a quarter within 9 and three quarters within 48.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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