Heart FailurePhase 4NCT04950569
Effect of Levosimendan on miRNAs Regulation in the Failing Hearts
A Phase 4 study testing levosimendan in people with Heart Failure, run by Tongji Hospital at 1 site in China.
Trial summary
Chronic heart failure is the terminal stage of various cardiovascular diseases. It is characterized with high fatality rate and high recurrence rate, which brings a heavy economic burden to patients and society. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Heart Failure
- What is being tested?
- levosimendan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 136 participants
- Where
- 1 siteChina
- Study dates
- 29 Oct 2020to 30 Jun 2022
- Phase
- Phase 4
- 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
- Age over 18 years old, no gender limit;
- A clear diagnosis of chronic systolic heart failure with heart function NYHA III-IV (including medical history, clinical symptoms, and signs) by two attending physicians or above the level of attending ;
- Left ventricular ejection fraction (LVEF) <40%;
- Plasma NT-proBNP>1000 ng/L;
- Participate voluntarily and sign an informed consent form, and can be followed up for more than 6 months.
Who cannot join
- NYHA Class I-II of cardiac function;
- Acute myocardial infarction occurred in the past month;
- Unstable angina pectoris;
- Patients with acute pulmonary edema or acute hemodynamic disturbance;
- Right heart failure due to lung disease;
- Patients who are going to undergo heart transplantation or cardiac resynchronization therapy (CRT), or those who have received CRT treatment;
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- Female patients who have or plan to become pregnant;
- Those who have participated in any drug clinical trials within the previous 3 months;
- Those who have a history of tumors or are currently suffering from tumors, or pathological examinations have confirmed precancerous lesions (such as ductal carcinoma in situ of the breast, or dysplasia of the cervix);
- Patients who was detected with a malignant mass in the body through examination (physical examination, or X-ray examination or B-ultrasound examination or other means), or detected with a hyperplastic gland or adenoma that has endocrine activity and affects heart function or endocrine function, such as pheochromocytoma, etc.;
- The patient refused to comply with the requirements of this research to complete the research work;
- According to the judgment of the investigator, the patient cannot complete the study or cannot comply with the requirements of the study (due to management reasons or other reasons).
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Tongji Hospital
Wuhan, Hubei, 430030
Li Ni, 13407192299, nili@tjh.tjmu.edu.cn
About this study
Official title: Levosimendan Improves Heart Failure Through Regulating 3 Cardiac Specific miRNAs (miR-660-3p, miR-665 and miR-1285-3p) in Patients With Refractory Heart Failure (NYHA III-IV)
Chronic heart failure is the terminal stage of various cardiovascular diseases. It is characterized with high fatality rate and high recurrence rate, which brings a heavy economic burden to patients and society. Although in recent years, the long-term prognosis of patients with heart failure has been greatly improved by the advances in drugs and new techniques, some patients have eventually progressed to refractory heart failure.
The newly developed positive inotropic drug levosimendan is a new type of calcium sensitizer, increasing the sensitivity of troponin to calcium ions, without directly increasing the concentration of calcium ions in cardiomyocytes. Levosimendan improves heart function by increasing myocardial contractility, dilating blood vessels, regulating coronary blood flow, and also exhibits anti-inflammatory, anti-oxidant and anti-apoptotic effects. Compared with traditional inotropic drugs, levosimendan does not increase calcium ion concentration or increase oxygen consumption. And it does not easily lead to malignant arrhythmia or increase the long-term mortality of patients. Because of its long half-life, intermittent use of levosimendan can improve contractile function for a long time, thereby effectively alleviating the symptoms of patients with advanced heart failure. Patients treated with levosimendan had a higher survival rate, fewer hospitalizations, and a greatly improved quality of life.
Read more
MicroRNAs (miRNAs) are a class of non-coding RNAs with important regulatory roles. They are 22-nucleotide single-stranded RNAs derived from endogenous hairpin structure transcripts. MiRNAs are reported to be involved in the pathological process of heart remodeling. MiRNAs can be secreted by cells into the peripheral blood and exist stably, which can be used as new diagnostic markers for various diseases. The investigators have previously conducted simultaneous detection of miRNAs in myocardial tissue and peripheral blood in patients with heart failure, and conducted an epidemiological follow-up study. The investigators have identified three cardiac-specific secretory miRNAs (miR-660-3p, miR-665 and miR-1285-3p) which are significantly up-regulated in the plasma of patients with chronic heart failure. Subsequent analysis proved them as valuable biomarkers for the diagnosis and prognosis of heart failure.
The investigators hypothesis that the new positive inotropic drug levosimendan improve heart function by regulating the miRNAs in patients with heart failure. This study aims to treat patients with advanced heart failure with levosimendan. By combining the expression of myocardial specific miRNAs, myocardial injury markers, hemodynamics, patient symptoms, long-term prognosis and other clinical indicators, the investigators will explore the relationship between the three myocardial-specific miRNAs expression and cardiac function improvement by levosimendan treatment.
- Conditions
- Heart Failure
- Being tested
- levosimendan
- Keywords
- Heart Failure, Levosimendan, MicroRNA
- 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
On the basis of standard conventional anti-heart failure treatment, levosimendan was used for 24 hours. The first load was 12 μg/kg, intravenous injection for 10 minutes, followed by intravenous infusion of 0.1 μg/Kg/min for 24 hours.
| Study group | Role | What they receive |
|---|---|---|
| Levosimendan | Experimental | Receive standard heart failure treatment, plus levosimendan treatment. Receives: Drug: levosimendan |
| Control | No intervention | Receive standard heart failure treatment, without levosimendan treatment. |
What is being measured
The primary outcome is the main question the study is designed to answer.
NT-proBNP
Change of blood N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level in 7 days
Measured: From the day before levosimendan treatment to the 7th day after levosimendan treatment.
Secondary outcomes (4)
miR-660-3p, miR-665 and miR-1285-3p
Levels of the 3 cardiac specific miRNAs (miR-660-3p, miR-665 and miR-1285-3p) in blood, denoted as the fold change of the miRNA (miR-660-3p, miR-665 and miR-1285-3p) read copies over the the mRNA read copy of U6 promoter (loading control).
Measured: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
Left ventricular ejection fraction
Left ventricular ejection fraction by echocardiography to evaluate cardiac function
Measured: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
NYHA
Assessment of cardiac function by New York Heart Association (NYHA) classification. Cardiac function is assessed from Class I to Class IV by NYHA. Higher class indicates worse cardiac function.
Measured: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
6 minutes walking distance
Assessment of cardiac function by 6 minutes walking distance
Measured: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jul 2021
- Study start29 Oct 2020
- Primary completion30 Jun 2022 (estimated)
- Study completion30 Jun 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Heart FailureStudies of the same condition, open and under way.
- More trials run by Tongji HospitalThe 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 136 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Tongji Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Li Ni, Tongji Hospital
- Investigators
- Li Ni, Principal investigator, Tongji Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04950569
- Sponsor's protocol ID
- TJ-LS-HF
- Status last verified
- Jul 2021
- First submitted
- 24 Jun 2021
- Last updated
- 16 Jul 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Levosimendan Improves Heart Failure Through Regulating 3 Cardiac Specific miRNAs (miR-660-3p, miR-665 and miR-1285-3p) in Patients With Refractory Heart Failure (NYHA III-IV)
- ClinicalTrials.gov ID
- NCT04950569
- Acronym / sponsor ID
- TJ-LS-HF
- Conditions
- Heart Failure
- Keywords
- Heart Failure, Levosimendan, MicroRNA
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 136 participants (estimated)
- Lead sponsor
- Tongji HospitalUniversity, hospital or other
- Study start
- 29 Oct 2020 (actual)
- Primary completion
- 30 Jun 2022 (estimated)
- Study completion
- 30 Jun 2022 (estimated)
- First posted
- 6 Jul 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.
Chronic heart failure is the terminal stage of various cardiovascular diseases. It is characterized with high fatality rate and high recurrence rate, which brings a heavy economic burden to patients and society. Although in recent years, the long-term prognosis of patients with heart failure has been greatly improved by the advances in drugs and new techniques, some patients have eventually progressed to refractory heart failure.
The newly developed positive inotropic drug levosimendan is a new type of calcium sensitizer, increasing the sensitivity of troponin to calcium ions, without directly increasing the concentration of calcium ions in cardiomyocytes. Levosimendan improves heart function by increasing myocardial contractility, dilating blood vessels, regulating coronary blood flow, and also exhibits anti-inflammatory, anti-oxidant and anti-apoptotic effects. Compared with traditional inotropic drugs, levosimendan does not increase calcium ion concentration or increase oxygen consumption. And it does not easily lead to malignant arrhythmia or increase the long-term mortality of patients. Because of its long half-life, intermittent use of levosimendan can improve contractile function for a long time, thereby effectively alleviating the symptoms of patients with advanced heart failure. Patients treated with levosimendan had a higher survival rate, fewer hospitalizations, and a greatly improved quality of life.
MicroRNAs (miRNAs) are a class of non-coding RNAs with important regulatory roles. They are 22-nucleotide single-stranded RNAs derived from endogenous hairpin structure transcripts. MiRNAs are reported to be involved in the pathological process of heart remodeling. MiRNAs can be secreted by cells into the peripheral blood and exist stably, which can be used as new diagnostic markers for various diseases. The investigators have previously conducted simultaneous detection of miRNAs in myocardial tissue and peripheral blood in patients with heart failure, and conducted an epidemiological follow-up study. The investigators have identified three cardiac-specific secretory miRNAs (miR-660-3p, miR-665 and miR-1285-3p) which are significantly up-regulated in the plasma of patients with chronic heart failure. Subsequent analysis proved them as valuable biomarkers for the diagnosis and prognosis of heart failure.
The investigators hypothesis that the new positive inotropic drug levosimendan improve heart function by regulating the miRNAs in patients with heart failure. This study aims to treat patients with advanced heart failure with levosimendan. By combining the expression of myocardial specific miRNAs, myocardial injury markers, hemodynamics, patient symptoms, long-term prognosis and other clinical indicators, the investigators will explore the relationship between the three myocardial-specific miRNAs expression and cardiac function improvement by levosimendan treatment.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Levosimendan | Experimental | Drug: levosimendanReceive standard heart failure treatment, plus levosimendan treatment. |
| Control | No intervention | –Receive standard heart failure treatment, without levosimendan treatment. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age over 18 years old, no gender limit;
- A clear diagnosis of chronic systolic heart failure with heart function NYHA III-IV (including medical history, clinical symptoms, and signs) by two attending physicians or above the level of attending ;
- Left ventricular ejection fraction (LVEF) <40%;
- Plasma NT-proBNP>1000 ng/L;
- Participate voluntarily and sign an informed consent form, and can be followed up for more than 6 months.
Key exclusion criteria (12 listed)
- NYHA Class I-II of cardiac function;
- Acute myocardial infarction occurred in the past month;
- Unstable angina pectoris;
- Patients with acute pulmonary edema or acute hemodynamic disturbance;
- Right heart failure due to lung disease;
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 |
|---|---|---|
| levosimendanOn the basis of standard conventional anti-heart failure treatment, levosimendan was used for 24 hours. The first load was 12 μg/kg, intravenous injection for 10 minutes, followed by intravenous infusion of 0.1 μg/Kg/min for 24 hours. | Drug | Levosimendan |
Primary outcome
NT-proBNP
Time frame: From the day before levosimendan treatment to the 7th day after levosimendan treatment.
Change of blood N-terminal prohormone of brain natriuretic peptide (NT-proBNP) level in 7 days
4 secondary outcomes
miR-660-3p, miR-665 and miR-1285-3p
Time frame: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
Left ventricular ejection fraction
Time frame: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
NYHA
Time frame: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
6 minutes walking distance
Time frame: From the day before levosimendan treatment to the 6th month after levosimendan treatment.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Jul 2021.
- 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.
Li Ni principal investigator
Tongji Hospital
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 Tongji Hospital at 1 site in China.
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 5 inclusion and 12 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: status not confirmed, as of the sponsor's last update on 16 Jul 2021. 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 China. 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.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Li Ni (13407192299, nili23@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
NT-proBNP (time frame: From the day before levosimendan treatment to the 7th day after levosimendan treatment.). 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 16 Jul 2021.