Heart FailurePhase 4NCT02261948
Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)
A Phase 4 study testing Levosimendan in people with Heart Failure, run by Centro Cardiologico Monzino at 1 site in Italy.
Trial summary
The present study was conceived to evaluate the effects of levosimendan on cardiopulmonary exercise test (CPET) and DLCO ( Diffusion capacity of Lung for carbon monoxide) in patients with severe heart failure in stable clinical conditions (NYHA - New York Heart Association - class III, with a peak VO2 (Oxygen… Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Heart Failure
- What is being tested?
- Levosimendan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 42 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2012to Dec 2014
- Phase
- Phase 4
- 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 18 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- informed consent of the study signed
- severe heart failure in stable clinical condition (NYHA class III, peak VO2 <12 ml / kg / min) in optimized medical therapy. The clinical stability is defined by the stability of the therapy, the weight and urine output for 3 days
Who cannot join
- unstable patients from a clinical point of view, not in optimized therapy
- patients unable to perform a CPET (Cardiopulmonary Exercise Test) .
- are excluded from the protocol also patients with absolute contraindications to CPET (acute myocardial infarction, severe aortic stenosis, myocarditis or pericarditis, active, acute thromboembolism, sepsis,unstable angina, uncontrolled arrhythmia.
- age < 18 years.
Trial locations and contacts
1 site in 1 country.
About this study
The present study was conceived to evaluate the effects of levosimendan on cardiopulmonary exercise test (CPET) and DLCO ( Diffusion capacity of Lung for carbon monoxide) in patients with severe heart failure in stable clinical conditions (NYHA - New York Heart Association - class III, with a peak VO2 (Oxygen consumption ) < 12 ml/min/kg) on top of optimized standard therapy.
Read the detailed description
Eligible patients should have chronic HF (Heart Failure -class NYHA III or IV) in stable clinical conditions. Inclusion criteria were: left ejection fraction (EF) at echocardiography ≤35%, age ≥18 years old, peak VO2 <12 ml/min/kg measured by a CPET, a standard optimized therapy for HF that include ACE-inhibitors, ARBs (angiotensin II Receptor Blocker), aldosterone blocking agents (spironolactone), diuretics, and beta-blockers.
The exclusion criteria are: ongoing mechanical ventilation; recent or acute coronary syndromes; sustained ventricular tachycardia or ventricular fibrillation; severe aortic or mitral regurgitation, or known malfunctioning artificial heart valve; uncorrected obstructive valvular disease; hypertrophic obstructive cardiomyopathy; uncorrected thyroid disease.
Patients will be randomly assigned by means of prepared letters to the levosimendan or placebo group stratified by clinical centre in a 1:1 allocation using block randomization. The placebo infusion will be coloured identically to its respective active counterpart. Patients and investigators will be kept blinded to the treatment allocation for the entire duration of the trial. Study drug will be infused with an injection speed between 6 and 20 ml/min based on blood pressure, without a bolus, for 24 hours.
Medical history, physical examination and a blood sample examination will be recorded: NYHA class, BNP (Brain Natriuretic Peptide), haemoglobin, creatinine, blood urea nitrogen (BUN) will be recorded before and 24 hours after the drug infusion.
A two-dimensional standard echocardiography evaluation will be performed at the admission in the hospital.
A maximal CPET performed on a cycle ergometer (Sensor Medics Ergo 800S and V-max, Yorba-Linda, CA) with a personalized ramp aimed at achieving peak exercise in 10 minutes will be performed before and 24 hours after the drug infusion. Expiratory O2, CO2 (Carbon dioxide) and ventilation (VE) will be measured breath by breath. Peak VO2 (Carbon dioxide production) was considered to be the highest VO2 achieved during the exercise. A 12-lead electrocardiogram will be also recorded. Spirometry and DLCO measurements will be performed before ad 24-hours after the drug infusion. . DLCO will be measured by the single breath-constant expiratory flow technique
- Conditions
- Heart Failure
- Being tested
- Levosimendan, Placebo
- Keywords
- Cardiac Failure, Severe Heart Failure
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LevosimendanDrug
Also called SIMDAX
Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min.
PlaceboDrug
Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min.
| Study group | Role | What they receive |
|---|---|---|
| Levosimendan | Active comparator | Levosimendan must be diluted before the administration (500 ml of glucose). The intravenous infusion may be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response. Receives: Drug: Levosimendan |
| Placebo | Placebo comparator | Placebo must be diluted before the administration (500 ml of glucose). The intravenous infusion may' be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Peak VO2 (Oxygen Consumption )
Primary endpoints: Levosimendan induced changes in peak VO2 (Oxygen consumption )
Measured: 48 hours
Secondary outcomes (2)
Changes in VE/VCO2
Levosimendan induced changes on VE/VCO2 (VE: Expired Volume - VCO2: carbon dioxide production) relationship
Measured: 48 hours
Change in DLCO (Diffusion Lung CO)
Levosimendan induced changes on DLCO ( Diffusion Lung CO). DLCO is measured by the single breath-constant expiratory flow technique (Sensor Medics 2200, Yorba Linda, CA) and we calculate also the DLCO adjusted for hemoglobin. Dilution of CH4 is used to measure alveolar volume.
Measured: 48 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Oct 2014 (estimated)
- Study startSep 2012
- Primary completionSep 2014
- Study completionDec 2014
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.
- Other trials for Heart FailureStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 42 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centro Cardiologico Monzino
- Sponsor type
- University, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Responsible party
- Principal investigator, Piergiuseppe Agostoni, Centro Cardiologico Monzino
- Investigators
- Piergiuseppe Agostoni, MD, PhD, Principal investigator, Centro Cardiologico Monzino,IRCCS
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02261948
- Sponsor's protocol ID
- CCFM 199/312
- Status last verified
- Oct 2015
- First submitted
- 22 Jul 2014
- Last updated
- 6 Nov 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levosimendan Efficacy Assessment by Cardiopulmonary Exercise Test (CPET)
- ClinicalTrials.gov ID
- NCT02261948
- Acronym / sponsor ID
- CCFM 199/312
- Conditions
- Heart Failure
- Keywords
- Cardiac Failure, Severe Heart Failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants (actual)
- Lead sponsor
- Centro Cardiologico MonzinoUniversity, hospital or other
- Collaborators
- Orion Corporation, Orion Pharma
- Study start
- Sep 2012
- Primary completion
- Sep 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Oct 2014 (estimated)
- Results
- Posted 6 Nov 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The present study was conceived to evaluate the effects of levosimendan on cardiopulmonary exercise test (CPET) and DLCO ( Diffusion capacity of Lung for carbon monoxide) in patients with severe heart failure in stable clinical conditions (NYHA - New York Heart Association - class III, with a peak VO2 (Oxygen consumption ) < 12 ml/min/kg) on top of optimized standard therapy.
Detailed description
Eligible patients should have chronic HF (Heart Failure -class NYHA III or IV) in stable clinical conditions. Inclusion criteria were: left ejection fraction (EF) at echocardiography ≤35%, age ≥18 years old, peak VO2 <12 ml/min/kg measured by a CPET, a standard optimized therapy for HF that include ACE-inhibitors, ARBs (angiotensin II Receptor Blocker), aldosterone blocking agents (spironolactone), diuretics, and beta-blockers.
The exclusion criteria are: ongoing mechanical ventilation; recent or acute coronary syndromes; sustained ventricular tachycardia or ventricular fibrillation; severe aortic or mitral regurgitation, or known malfunctioning artificial heart valve; uncorrected obstructive valvular disease; hypertrophic obstructive cardiomyopathy; uncorrected thyroid disease.
Patients will be randomly assigned by means of prepared letters to the levosimendan or placebo group stratified by clinical centre in a 1:1 allocation using block randomization. The placebo infusion will be coloured identically to its respective active counterpart. Patients and investigators will be kept blinded to the treatment allocation for the entire duration of the trial. Study drug will be infused with an injection speed between 6 and 20 ml/min based on blood pressure, without a bolus, for 24 hours.
Medical history, physical examination and a blood sample examination will be recorded: NYHA class, BNP (Brain Natriuretic Peptide), haemoglobin, creatinine, blood urea nitrogen (BUN) will be recorded before and 24 hours after the drug infusion.
A two-dimensional standard echocardiography evaluation will be performed at the admission in the hospital.
A maximal CPET performed on a cycle ergometer (Sensor Medics Ergo 800S and V-max, Yorba-Linda, CA) with a personalized ramp aimed at achieving peak exercise in 10 minutes will be performed before and 24 hours after the drug infusion. Expiratory O2, CO2 (Carbon dioxide) and ventilation (VE) will be measured breath by breath. Peak VO2 (Carbon dioxide production) was considered to be the highest VO2 achieved during the exercise. A 12-lead electrocardiogram will be also recorded. Spirometry and DLCO measurements will be performed before ad 24-hours after the drug infusion. . DLCO will be measured by the single breath-constant expiratory flow technique
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levosimendan | Active comparator | Drug: LevosimendanLevosimendan must be diluted before the administration (500 ml of glucose). The intravenous infusion may be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response. |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo must be diluted before the administration (500 ml of glucose). The intravenous infusion may' be administered either by the peripheral or central. The dose and duration of therapy should be decided according to the patient's clinical condition and response to the drug. Treatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. A low infusion bolus (6 mcg / kg) is recommended for patients who have a concomitant intravenous treatment with vasodilators or inotropic. The patient's response should be evaluated during the infusion bolus or within 30 to 60 minutes and a dose adjustment based on clinical response. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- informed consent of the study signed
- severe heart failure in stable clinical condition (NYHA class III, peak VO2 <12 ml / kg / min) in optimized medical therapy. The clinical stability is defined by the stability of the therapy, the weight and urine output for 3 days
Key exclusion criteria (4 listed)
- unstable patients from a clinical point of view, not in optimized therapy
- patients unable to perform a CPET (Cardiopulmonary Exercise Test) .
- are excluded from the protocol also patients with absolute contraindications to CPET (acute myocardial infarction, severe aortic stenosis, myocarditis or pericarditis, active, acute thromboembolism, sepsis,unstable angina, uncontrolled arrhythmia.
- age < 18 years.
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: SIMDAXTreatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. | Drug | Levosimendan |
| PlaceboTreatment should be initiated with a loading dose of 6-12 mcg / kg infused over 10 minutes followed by a continuous infusion of 0.1 mcg / kg / min. | Drug | Placebo |
Primary outcome
Change in Peak VO2 (Oxygen Consumption )
Time frame: 48 hours
Primary endpoints: Levosimendan induced changes in peak VO2 (Oxygen consumption )
2 secondary outcomes
Changes in VE/VCO2
Time frame: 48 hours
Change in DLCO (Diffusion Lung CO)
Time frame: 48 hours
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Piergiuseppe Agostoni, MD, PhD principal investigator
Centro Cardiologico Monzino,IRCCS
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Levosimendan in people with Heart Failure, run by Centro Cardiologico Monzino at 1 site in Italy.
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 6 Nov 2015. 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 Italy. 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. Some participants in this study may receive a placebo. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 6 Nov 2015). 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?
Change in Peak VO2 (Oxygen Consumption ) (time frame: 48 hours). 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 6 Nov 2015.