Acute Heart FailurePhase 2EASI-ChildNCT04405804
Early Administration of Ivabradine in Children With Heart Failure
A Phase 2 study testing Ivabradine 5Mg Tab in people with Acute Heart Failure and Dilated Cardiomyopathy, run by Bambino Gesù Hospital and Research Institute at 1 site in Italy.
Trial summary
This is a monocentric, prospective, single arm, not for profit study. It is designed to study the early use of ivabradine in patients with dilated cardiomyopathy and Ejection Fraction (EF) < 45%. Read more about this study
- Who is it for?
- Ages 6 months to 17 years
- Conditions the study is for
- Acute Heart Failure, Dilated Cardiomyopathy
- What is being tested?
- Ivabradine 5Mg Tab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 9 participants
- Where
- 1 siteItaly
- Study dates
- 20 Jun 2020to May 2021
- Phase
- Phase 2
- 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 6 months to 17 years
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Dilated cardiomyopathy defined according to the indications of the Cardiomyopathy Task Force (dilation > 2 Standard Deviations (SD) and hypokinesia);
- Class NYHA/Ross ≥ II;
- Ejection fraction < 40%;
- Patients with acute heart failure episodes (both new episode and relapse) in the last three months;
- Systolic blood pressure > 50° age and height;
- Heart rate: 6-12 months: ≥105 bpm, >1 year <3 years: ≥95 bpm, 3-5 years: ≥75 bpm, 5-18 years: >70 bpm.
Who cannot join
- Cardiogenic shock in the three months;
- Hypertrophic, restrictive or mixed cardiomyopathy;
- Acute lymphocytic myocarditis diagnosed with endomyocardial biopsy;
- Significant Valvular Pathology;
- Sinus block and congenital long QT syndrome;
- Atrial Fibrillation;
Show all 12Show fewer
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels > 2.5 times normal, bilirubin > 3 and creatinine > 2.5 mg/dL;
- Pregnancy and/or positive pregnancy test patients;
- Hypersensitivity to the active substance or any of the excipients;
- Participation in a clinical trial in which an experimental drug was administered within 30 days or 5 half-lives of the investigational drug;
- Chronic lung disease or other clinical condition that the investigating physician believes is incompatible with the study;
- eGFR <15 mL/min/1.73 m2.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Monocentric, Open Label, Single Arm, Pilot Study on the Early Administration of Ivabradine in Children Aged >6 Months and <18 Years With Dilated Cardiomyopathy and Acute Heart Failure
This is a monocentric, prospective, single arm, not for profit study. It is designed to study the early use of ivabradine in patients with dilated cardiomyopathy and Ejection Fraction (EF) < 45%.
Read the detailed description
The study is divided into a screening and enrollment visit (V1) where eligibility for treatment will be confirmed. Ivabradine will be administered to eligible patients with increasing dosage during the titration period (TP) which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period (MP) of the drug for a further 14 days. The follow-up period (FU) will last 4 months.
The dose of ACE inhibitors will be introduced after 72 hours of clinical stability after the introduction of titrated ivabradine at maximum dose according to protocol. The anti-aldosterone will be introduced 24 hours after the introduction of ivabradine. The diuretic will not be modified during the titration phase of the drug, unless there is clinical necessity.
During the FU ivabradine will be continued at stable dosage, in order to maintain the target heart rate (HR) reached during the maintenance phase (HR > 80 bpm, in the group of patients older than 6-12 months, or HR > 70 bpm in patients aged 1-3 years or HR > 50 bpm between 3-18 years). In all patients, the drug dose will be decreased or discontinued in case of bradycardia (HR< 80 bpm in patients 6-12 months, HR< 70 bpm in patients 1-3 years of age or HR< 60 bpm in patients 3-18 years of age) and/or symptoms related to bradycardia or for other safety reasons.
- Conditions
- Acute Heart Failure, Dilated Cardiomyopathy
- Being tested
- Ivabradine 5Mg Tab
- Keywords
- Ivabradine, Heart Failure, Pediatric, Cardiomyopathy
- Medical subject headings
- Cardiomyopathy, Dilated, Heart Failure, Cardiomyopathies
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivabradine 5Mg TabDrug
Initial dose of ivabradine will be:
0.02 mg/kg/dose twice daily in patients between 6-12 months 0.05 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 2.5 mg/day in patients between 3-18 years with weight > 40 kg During titration phase, the dose may be increased, maintained, reduced or discontinued in accordance with titration rules. The titration rules will be adjusted on the basis of age subset and of each patient's evaluation during the titration phase, whether or not the target heart rate is reached (HR ≥ 20% compared to baseline HR) and whether or not are present bradycardia (HR should be greater than predefined by a HR threshold per age subset) and/or bradycardia-related symptoms.
Maximum dose to be reached will be:
0.2 mg/kg/dose twice daily in patients between 6-12 months 0.3 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 15 mg/day in patients between 3-18 years, weight > 40 kg
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Experimental | Eligible patients will be given treatment with ivabradine during a titration period which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period of another 14 days. At the end of maintenance period, primary endpoint will be assessed. After maintenance period, the patient will continue ivabradine at the same dosage during a follow-up period that will last 4 months. Receives: Drug: Ivabradine 5Mg Tab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
To assess the response to ivabradine on heart rate after 14 days of stable therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Secondary outcomes (14)
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up
To assess the response to ivabradine on heart rate after 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance
To assess the response to ivabradine on serum NT-proBNP levels after 14 days of stable therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up
To assess the response to ivabradine on serum NT-proBNP levels after 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance
To assess the correlation between heart rate and serum NT-proBNP levels after 14 days of stable therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up
To assess the correlation between heart rate and serum NT-proBNP levels after 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of maintenance
To assess EF, Left Ventricular End Diastolic Volume (LVEDV), Left Ventricular End Systolic Volume (LVESV) after 14 days of stable therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of follow-up
To assess EF, LVSV, LVDV after 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance
To assess the response to ivabradine on systolic blood pressure after 14 days of stable therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up
To assess the response to ivabradine on systolic blood pressure after 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)
To assess the need to resort to inotropic drugs within 14 days of stable ivabradine therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)
To assess the need to resort to inotropic drugs within 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Number and % of dropouts at the end of maintenance
To assess the frequency of patients who exit from the study within 14 days of stable ivabradine therapy
Measured: At the end of the two weeks maintenance period (17-29 days from enrollment)
Number and % of dropouts at the end of follow-up
To assess the frequency of patients who exit from the study within 16 weeks of follow-up
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Time (days) from start of ivabradine therapy and new episode of acute heart failure, and/or implantation of mechanical assist device at the end of follow up
To assess the period within main cardiological events would occur after the start of ivabradine therapy
Measured: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 May 2020
- Study start20 Jun 2020
- Primary completionJan 2021 (estimated)
- Study completionMay 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Simon's two-stage design
- Masking
- None (open label)
- Enrolment
- 9 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Bambino Gesù Hospital and Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Ministero della Salute, Italy
- Responsible party
- Principal investigator, Rachele Adorisio, Bambino Gesù Hospital and Research Institute
- Investigators
- Rachele Adorisio, MD, Principal investigator, Bambino Gesù Hospital and Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04405804
- Sponsor's protocol ID
- 1986 / 2019
- Other IDs
- 2019-003902-29, 2019
- Acronym
- EASI-Child
- Status last verified
- Dec 2020
- First submitted
- 26 May 2020
- Last updated
- 8 Dec 2020
- Results posted
- No
- Data monitoring committee
- Yes
- 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 8 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Monocentric, Open Label, Single Arm, Pilot Study on the Early Administration of Ivabradine in Children Aged >6 Months and <18 Years With Dilated Cardiomyopathy and Acute Heart Failure
- ClinicalTrials.gov ID
- NCT04405804
- Acronym / sponsor ID
- EASI-Child / 1986 / 2019
- Conditions
- Acute Heart Failure, Dilated Cardiomyopathy
- Keywords
- Ivabradine, Heart Failure, Pediatric, Cardiomyopathy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 9 participants (estimated)
- Lead sponsor
- Bambino Gesù Hospital and Research InstituteUniversity, hospital or other
- Collaborators
- Ministero della Salute, Italy
- Study start
- 20 Jun 2020 (actual)
- Primary completion
- Jan 2021 (estimated)
- Study completion
- May 2021 (estimated)
- First posted
- 28 May 2020 (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.
This is a monocentric, prospective, single arm, not for profit study. It is designed to study the early use of ivabradine in patients with dilated cardiomyopathy and Ejection Fraction (EF) < 45%.
Detailed description
The study is divided into a screening and enrollment visit (V1) where eligibility for treatment will be confirmed. Ivabradine will be administered to eligible patients with increasing dosage during the titration period (TP) which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period (MP) of the drug for a further 14 days. The follow-up period (FU) will last 4 months.
The dose of ACE inhibitors will be introduced after 72 hours of clinical stability after the introduction of titrated ivabradine at maximum dose according to protocol. The anti-aldosterone will be introduced 24 hours after the introduction of ivabradine. The diuretic will not be modified during the titration phase of the drug, unless there is clinical necessity.
During the FU ivabradine will be continued at stable dosage, in order to maintain the target heart rate (HR) reached during the maintenance phase (HR > 80 bpm, in the group of patients older than 6-12 months, or HR > 70 bpm in patients aged 1-3 years or HR > 50 bpm between 3-18 years). In all patients, the drug dose will be decreased or discontinued in case of bradycardia (HR< 80 bpm in patients 6-12 months, HR< 70 bpm in patients 1-3 years of age or HR< 60 bpm in patients 3-18 years of age) and/or symptoms related to bradycardia or for other safety reasons.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Simon's two-stage design
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Experimental | Drug: Ivabradine 5Mg TabEligible patients will be given treatment with ivabradine during a titration period which will last from a minimum of 3 days to a maximum of 15 days. This will be followed by a maintenance period of another 14 days. At the end of maintenance period, primary endpoint will be assessed. After maintenance period, the patient will continue ivabradine at the same dosage during a follow-up period that will last 4 months. |
Who may qualify
- Ages
- 6 months to 17 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (6 listed)
- Dilated cardiomyopathy defined according to the indications of the Cardiomyopathy Task Force (dilation > 2 Standard Deviations (SD) and hypokinesia);
- Class NYHA/Ross ≥ II;
- Ejection fraction < 40%;
- Patients with acute heart failure episodes (both new episode and relapse) in the last three months;
- Systolic blood pressure > 50° age and height;
Key exclusion criteria (12 listed)
- Cardiogenic shock in the three months;
- Hypertrophic, restrictive or mixed cardiomyopathy;
- Acute lymphocytic myocarditis diagnosed with endomyocardial biopsy;
- Significant Valvular Pathology;
- Sinus block and congenital long QT syndrome;
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 |
|---|---|---|
| Ivabradine 5Mg TabInitial dose of ivabradine will be: 0.02 mg/kg/dose twice daily in patients between 6-12 months 0.05 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 2.5 mg/day in patients between 3-18 years with weight > 40 kg During titration phase, the dose may be increased, maintained, reduced or discontinued in accordance with titration rules. The titration rules will be adjusted on the basis of age subset and of each patient's evaluation during the titration phase, whether or not the target heart rate is reached (HR ≥ 20% compared to baseline HR) and whether or not are present bradycardia (HR should be greater than predefined by a HR threshold per age subset) and/or bradycardia-related symptoms. Maximum dose to be reached will be: 0.2 mg/kg/dose twice daily in patients between 6-12 months 0.3 mg/kg/dose twice daily in patients between 1-3 years and 3-18 years with a weight < 40 kg 15 mg/day in patients between 3-18 years, weight > 40 kg | Drug | Ivabradine |
Primary outcome
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
To assess the response to ivabradine on heart rate after 14 days of stable therapy
14 secondary outcomes
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Serum NT-proBNP in pg/mL (mean (±SD) difference from baseline) at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Correlation between heart rate and NT-proBNP value (Pearson correlation) at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Left ventricular function, calculated by 2D echocardiographic technique (calculation of left ventricular volume and ejection fraction - mean (±SD) difference from baseline) at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Systolic blood pressure in mmHg (mean (±SD) difference from baseline) at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of maintenance)
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Use of inotropic drugs (number and % of patients who had to use inotropes at the end of follow-up)
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Number and % of dropouts at the end of maintenance
Time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)
Number and % of dropouts at the end of follow-up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Time (days) from start of ivabradine therapy and new episode of acute heart failure, and/or implantation of mechanical assist device at the end of follow up
Time frame: At the end of the 16 weeks follow-up period (129-141 days from enrollment)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2020.
- Individual participant dataSharing planned: No
Related trials for Acute Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life(COREVIVE-HFrEF)
Heart Failure With Reduced Ejection Fraction, Iron Deficiency
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
Not yet recruitingPhase 3
Early Discharge With Subcutaneous Furosemide Versus Standard Care in Acute Heart Failure
Heart Failure, Acute Decompensated Heart Failure
Recruiting
CT Stress Myocardial Perfusion, Fractional Flow Reserve and Angiography in Patients With Stable Chest Pain Syndromes
Coronary Artery Disease, Chest Syndrome
Recruiting
WIN Ratio Analysis to Determine a Strategy of Non- Invasive SUpport for Respiratory Failure in the EmeRgency Department
Acute Hypoxic Respiratory Failure, Acute Respiratory Distress Syndrome (ARDS)
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.
Rachele Adorisio, MD principal investigator
Bambino Gesù Hospital and Research Institute
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Ivabradine 5Mg Tab in people with Acute Heart Failure and Dilated Cardiomyopathy, run by Bambino Gesù Hospital and Research Institute 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 6 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 8 Dec 2020. 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. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
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?
Heart rate in b.p.m. (mean (±SD) difference from baseline) at the end of maintenance (time frame: At the end of the two weeks maintenance period (17-29 days from enrollment)). 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 8 Dec 2020.