Cardiogenic ShockPhase 4ES-FISHNCT03437369
Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock
A Phase 4 study testing Ivabradine Oral Tablet in people with Cardiogenic Shock, run by Hospital Universitario Ramon y Cajal at 1 site in Spain.
Trial summary
This is a randomized 1:1 blinded study that evaluate in acute left heart failure-cardiogenic shock patients if ivabradine treatment can reduce pulmonary wedge pressure, without inducing a significant or relevant reduction in cardiac output or increasing the risk of arterial hypotension and with the benefit of allowing… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Cardiogenic Shock
- What is being tested?
- Ivabradine Oral Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 22 participants
- Where
- 1 siteSpain
- Study dates
- May 2018to Oct 2019
- 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
- Patients aged ≥ 18 years, with acute heart failure due to left ventricular systolic dysfunction (LVEF ≤ 40%) in sinus rhythm, baseline HR ≥ 90 bpm, with signs of low peripheral perfusion with indication for intravenous inotropic treatment (catecholamines: dobutamine , adrenaline, dopamine or noradrenaline) and admitted to the Cardiological Intensive Care Unit.
- Pharmacological treatment and stable hemodynamic situation in the 4 hours before inclusion.
- Pulmonary wedge pressure ≥ 18 mm Hg and systolic blood pressure > 90 mm Hg.
- Patient's signature on the consent form.
Who cannot join
- Previous treatment with ivabradine (< 48 hours).
- Known hypersensitivity to ivabradine.
- Cardiac rhythm different from sinus rhythm.
- Unstable cardiac rhythm due to paroxysmal atrial fibrillation or atrial flutter, very frequent ventricular or supraventricular premature beats, ventricular tachycardia, 2nd or 3rd degree atrioventricular (AV) block.
- Severe chronic renal failure (estimated glomerular filtration rate ≤15 ml / min) or on chronic treatment with dialysis.
- QT interval higher than 450 ms.
Show all 15Show fewer
- Sepsis as a probable mechanism of tachycardia and hypotension.
- Need for urgent cardiac surgery, planned within 72 hours of possible inclusion.
- Severe aortic stenosis or severe valvular disease that requires surgical correction.
- Patient must not have received an IV bolus of furosemide immediately before the baseline hemodynamic assessment.
- Severe hepatic insufficiency.
- Patient must not be participating in another clinical trial.
- Concomitant use of potent CYP3A4 inhibitors.
- Acute anemia or hypovolemia uncorrected.
- Pregnancy.
Trial locations and contacts
1 site in 1 country.
Spain1 site
Hospital Universitario Ramón y Cajal
Madrid, 28034
Marcelo Sanmartin, MD, +34 91 336 80 00, msanfer@me.com
Marina Pascual Izco, MD
About this study
Official title: Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock (ES-FISH)
This is a randomized 1:1 blinded study that evaluate in acute left heart failure-cardiogenic shock patients if ivabradine treatment can reduce pulmonary wedge pressure, without inducing a significant or relevant reduction in cardiac output or increasing the risk of arterial hypotension and with the benefit of allowing a faster titration of heart failure drugs.
- Conditions
- Cardiogenic Shock
- Being tested
- Ivabradine Oral Tablet, Standard of Care treatment
- Keywords
- Ivabradine, heart rate, acute heart failure
- Medical subject headings
- Shock, Cardiogenic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ivabradine Oral TabletDrug
The target dose is 10 to 15 mg / day, administered orally in two doses
Standard of Care treatmentOther
The study drug will be compared with the standard of Care treatment
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Experimental | Drug: Ivabradine Oral tablets 2.5 mg Dose: 10-15 mg/day Duration: 30 days Receives: Drug: Ivabradine Oral Tablet |
| Standard of Care | Other | The study drug will be compared with standard of Care treatment Receives: Other: Standard of Care treatment |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment.
Reduction of pulmonary wedge pressure from baseline in both treatment arms (ivabradine arm versus standard of care treatment measured by Swan Ganz balloon flotation catheter)
Measured: 24 hours
Secondary outcomes (9)
Severe bradycardia
-Development of excessive bradycardia defined as heart rate (HR) <50 beats per minute
Measured: 24 hours
Arrhythmias
New-onset of ventricular arrhythmias or atrial fibrillation
Measured: 24 hours
Hypotension
Hypotension, defined as systolic blood pressure <90 mmHg
Measured: 24 hours
Time to withdrawal of vasoactive drugs
-Time to catecholamine withdrawal in both treatment arms (days)
Measured: 30 days
Time needing invasive mechanical ventilation
Mechanical (invasive) ventilation time after initiation of ivabradine/control treatment.
Measured: 30 days
B-type natriuretic peptide (BNP)
Measured B-type natriuretic peptide (BNP) values at 30 days
Measured: 30 days
Left ventricular ejection fraction
Change in left ventricle ejection fraction from baseline in both treatment arms (%)
Measured: 30 days
Cardiovascular mortality
Mortality due to cardiovascular causes
Measured: 30 days
Total mortality
Mortality from any cause
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Feb 2018
- Study startMay 2018 (estimated)
- Primary completionOct 2019 (estimated)
- Study completionOct 2019 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Cardiogenic ShockStudies 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
- Double blind
- Who is masked
- Care provider, Investigator
- Enrolment
- 22 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitario Ramon y Cajal
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Marcelo Sanmartín Fernández, Hospital Universitario Ramon y Cajal
- Investigators
- Marcelo Sanmartín Fernández, PhD, Principal investigator, Hospital Universitario Ramon y Cajal
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03437369
- Sponsor's protocol ID
- HURamonyCajal
- Acronym
- ES-FISH
- Status last verified
- Feb 2018
- First submitted
- 15 Jan 2018
- Last updated
- 19 Feb 2018
- Results posted
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K; INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005 Dec;26(23):2529-36. doi: 10.1093/eurheartj/ehi586. Epub 2005 Oct 7.
PubMed 16214830Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.
PubMed 20801500Fasullo S, Cannizzaro S, Maringhini G, Ganci F, Giambanco F, Vitale G, Pinto V, Migliore G, Torres D, Sarullo FM, Paterna S, Di Pasquale P. Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings. J Card Fail. 2009 Dec;15(10):856-63. doi: 10.1016/j.cardfail.2009.05.013. Epub 2009 Jul 3.
PubMed 19944362Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001 Mar 13;103(10):1428-33. doi: 10.1161/01.cir.103.10.1428.
PubMed 11245648
Study at a glance
From the registry record, last updated by the sponsor on 19 Feb 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety on Heart Rate Control With Ivabradine on Cardiogenic Shock (ES-FISH)
- ClinicalTrials.gov ID
- NCT03437369
- Acronym / sponsor ID
- ES-FISH / HURamonyCajal
- Conditions
- Cardiogenic Shock
- Keywords
- Ivabradine, heart rate, acute heart failure
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 22 participants (estimated)
- Lead sponsor
- Hospital Universitario Ramon y CajalUniversity, hospital or other
- Study start
- May 2018 (estimated)
- Primary completion
- Oct 2019 (estimated)
- Study completion
- Oct 2019 (estimated)
- First posted
- 19 Feb 2018 (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 randomized 1:1 blinded study that evaluate in acute left heart failure-cardiogenic shock patients if ivabradine treatment can reduce pulmonary wedge pressure, without inducing a significant or relevant reduction in cardiac output or increasing the risk of arterial hypotension and with the benefit of allowing a faster titration of heart failure drugs.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Experimental | Drug: Ivabradine Oral TabletDrug: Ivabradine Oral tablets 2.5 mg Dose: 10-15 mg/day Duration: 30 days |
| Standard of Care | Other | Other: Standard of Care treatmentThe study drug will be compared with standard of Care treatment |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Patients aged ≥ 18 years, with acute heart failure due to left ventricular systolic dysfunction (LVEF ≤ 40%) in sinus rhythm, baseline HR ≥ 90 bpm, with signs of low peripheral perfusion with indication for intravenous inotropic treatment (catecholamines: dobutamine , adrenaline, dopamine or noradrenaline) and admitted to the Cardiological Intensive Care Unit.
- Pharmacological treatment and stable hemodynamic situation in the 4 hours before inclusion.
- Pulmonary wedge pressure ≥ 18 mm Hg and systolic blood pressure > 90 mm Hg.
- Patient's signature on the consent form.
Key exclusion criteria (15 listed)
- Previous treatment with ivabradine (< 48 hours).
- Known hypersensitivity to ivabradine.
- Cardiac rhythm different from sinus rhythm.
- Unstable cardiac rhythm due to paroxysmal atrial fibrillation or atrial flutter, very frequent ventricular or supraventricular premature beats, ventricular tachycardia, 2nd or 3rd degree atrioventricular (AV) block.
- Severe chronic renal failure (estimated glomerular filtration rate ≤15 ml / min) or on chronic treatment with dialysis.
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 Oral TabletThe target dose is 10 to 15 mg / day, administered orally in two doses | Drug | Ivabradine |
| Standard of Care treatmentThe study drug will be compared with the standard of Care treatment | Other | Standard of Care |
Primary outcome
Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment.
Time frame: 24 hours
Reduction of pulmonary wedge pressure from baseline in both treatment arms (ivabradine arm versus standard of care treatment measured by Swan Ganz balloon flotation catheter)
9 secondary outcomes
Severe bradycardia
Time frame: 24 hours
Arrhythmias
Time frame: 24 hours
Hypotension
Time frame: 24 hours
Time to withdrawal of vasoactive drugs
Time frame: 30 days
Time needing invasive mechanical ventilation
Time frame: 30 days
B-type natriuretic peptide (BNP)
Time frame: 30 days
Left ventricular ejection fraction
Time frame: 30 days
Cardiovascular mortality
Time frame: 30 days
Total mortality
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Feb 2018.
- Background: PubMed 16214830Tardif JC, Ford I, Tendera M, Bourassa MG, Fox K; INITIATIVE Investigators. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005 Dec;26(23):2529-36. doi: 10.1093/eurheartj/ehi586. Epub 2005 Oct 7.
- Background: PubMed 20801500Swedberg K, Komajda M, Bohm M, Borer JS, Ford I, Dubost-Brama A, Lerebours G, Tavazzi L; SHIFT Investigators. Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study. Lancet. 2010 Sep 11;376(9744):875-85. doi: 10.1016/S0140-6736(10)61198-1.
- Background: PubMed 19944362Fasullo S, Cannizzaro S, Maringhini G, Ganci F, Giambanco F, Vitale G, Pinto V, Migliore G, Torres D, Sarullo FM, Paterna S, Di Pasquale P. Comparison of ivabradine versus metoprolol in early phases of reperfused anterior myocardial infarction with impaired left ventricular function: preliminary findings. J Card Fail. 2009 Dec;15(10):856-63. doi: 10.1016/j.cardfail.2009.05.013. Epub 2009 Jul 3.
- Background: PubMed 11245648Lechat P, Hulot JS, Escolano S, Mallet A, Leizorovicz A, Werhlen-Grandjean M, Pochmalicki G, Dargie H. Heart rate and cardiac rhythm relationships with bisoprolol benefit in chronic heart failure in CIBIS II Trial. Circulation. 2001 Mar 13;103(10):1428-33. doi: 10.1161/01.cir.103.10.1428.
- 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.
Marcelo Sanmartín Fernández, PhD principal investigator
Hospital Universitario Ramon y Cajal
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 Ivabradine Oral Tablet in people with Cardiogenic Shock, run by Hospital Universitario Ramon y Cajal at 1 site in Spain.
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 4 inclusion and 15 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 19 Feb 2018. 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 Spain. 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 Marcelo Sanmartín Fernández, PhD (+34 91 336 80 00, msanfer@me.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes from baseline in pulmonary wedge pressure and cardiac output after 24h-treatment with ivabradine or standard of care treatment. (time frame: 24 hours). 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 NCT03437369, which also lists 4 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 19 Feb 2018.