NeoplasmsIPACNCT03650205
Ivabradine to Prevent Anthracycline-induced Cardiotoxicity
A study testing Ivabradine in people with Neoplasms and Heart Failure, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
Anthracyclines are associated with cardiotoxic effects. Previous studies suggest that enalapril, and or carvedilol, protect against cardiovascular effects of these drugs. Ivabradine selectively reduces heart rate through inhibition of the cardiac pace maker IF channel, thus prolonging the duration of spontaneous… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Neoplasms, Heart Failure, Cardiotoxicity
- What is being tested?
- Ivabradine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 160 participants
- Where
- 1 siteBrazil
- Study dates
- 22 Jan 2019to 1 Dec 2021
- Phase
- Interventional
- 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 to 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age 18-year-old or older;
- Cancer diagnosis;
- Chemotherapy with anthracycline;
- Written informed consent
Who cannot join
- Chronic Kidney Disease (Creatinine clearance inferior to 30mL/min/1.73m2)
- Bradycardia (heart rate less than 60 beats per minute)
- Atrial fibrilation;
- Previous diagnosis of heart failure;
- Pregnancy;
- History of previous hypersensibility to the study drug;
- Participating in another study protocol.
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Instituto do Cancer do Estado de Sao Paulo
São Paulo, São Paulo, 01246000
Stephanie I Rizk, MD, +551138933267, stephrizk@gmail.com
Ludhmila A Hajar, MD, PhD, +551138933267, ludhmila@terra.com.br
About this study
Official title: Ivabradine to Prevent Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial
Anthracyclines are associated with cardiotoxic effects. Previous studies suggest that enalapril, and or carvedilol, protect against cardiovascular effects of these drugs.
Ivabradine selectively reduces heart rate through inhibition of the cardiac pace maker IF channel, thus prolonging the duration of spontaneous depolarization in the sinus node. Additionally, ivabradine might preserve myocardial perfusion without negative inotropic effect and probably maintain cardiac contractility despite the reduction of heart rate.
Ivabradine has been shown to improve outcome in patients with heart failure and angina. The aim of this study is to evaluate whether ivabradine might prevent anthracycline-induced cardiotoxicity.
- Conditions
- Neoplasms, Heart Failure, Cardiotoxicity, Chemotherapy Effect, Oncology
- Being tested
- Ivabradine, Placebo
- Medical subject headings
- Neoplasms, Heart Failure, Cardiotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
Ivabradine capsule
PlaceboDrug
Also called Placebo oral capsule
Placebo oral capsule.
| Study group | Role | What they receive |
|---|---|---|
| Ivabradine | Active comparator | Patients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session. Receives: Drug: Ivabradine |
| Placebo | Placebo comparator | Patients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ventricular function
Reduction in global longitudinal strain of at least 10% (GLS)
Measured: 365 days after randomization
Secondary outcomes (7)
Composite endpoint of mortality or major cardiovascular outcomes
Composite endpoint of mortality or major cardiovascular outcomes (defined as acute myocardial infarction, heart failure, inappropriate sinus tachycardia and arrhythmia)
Measured: 365 days after randomization
Left ventricular dysfunction
Incidence of left ventricular (LV) dysfunction defined as reduction of LV ejection fraction by 10%.
Measured: 365 days after randomization
Incidence of myocardial injury
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Measured: 90 days after randomization
Incidence of myocardial injury
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Measured: 180 days after randomization
Incidence of myocardial injury
Levels of NT-proBNP and high-sensitivity cardiac troponin T
Measured: 365 days after randomization
Diastolic dysfunction
Assessment by echocardiography the incidence of diastolic dysfunction using the following parameters: peak E-wave velocity, peak A-wave velocity, mitral valve (MV) E/A ratio, MV deceleration time, pulsed-wave tissue doppler imaging e' velocity, Mitral E/e', left atrium maximum volume index, pulmonary vein(PV) systole(S) wave, PV diastole (D) wave, continuous wave (CW) doppler: tricuspid regurgitation, systolic jet velocity; Color M- mode.
Measured: 365 days after randomization
Ventricular function
Reduction in global longitudinal strain of at least 10% (GLS)
Measured: 180 days after randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Aug 2018
- Study start22 Jan 2019
- Primary completion1 Oct 2021 (estimated)
- Study completion1 Dec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of Sao PauloThe 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 160 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Ludhmila Abrahão Hajjar, University of Sao Paulo
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03650205
- Sponsor's protocol ID
- 42559415520020065
- Acronym
- IPAC
- Status last verified
- Apr 2019
- First submitted
- 13 Aug 2018
- Last updated
- 2 Apr 2019
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Rizk SI, Costa IBSDS, Cruz CBBV, Pileggi B, de Almeida Andrade FT, Gonzalez TB, Bittar CS, Fukushima JT, Quintao VC, Osawa EA, Alves JBS, Fonseca SMR, Garcia DR, Pereira J, Buccheri V, Avila J, Kawahara LT, Barros CCS, Ikeoka LT, Nakada LN, Fellini M, Rocha VG, Rego EM, Hoff PMG, Filho RK, Landoni G, Hajjar LA. Randomized, Placebo-Controlled, Triple-Blind Clinical Trial of Ivabradine for the Prevention of Cardiac Dysfunction During Anthracycline-Based Cancer Therapy. J Am Heart Assoc. 2025 May 20;14(10):e039745. doi: 10.1161/JAHA.124.039745. Epub 2025 May 13.
PubMed 40357644
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ivabradine to Prevent Anthracycline-induced Cardiotoxicity: a Randomized Clinical Trial
- ClinicalTrials.gov ID
- NCT03650205
- Acronym / sponsor ID
- IPAC / 42559415520020065
- Conditions
- Neoplasms, Heart Failure, Cardiotoxicity, Chemotherapy Effect, Oncology
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 160 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Study start
- 22 Jan 2019 (actual)
- Primary completion
- 1 Oct 2021 (estimated)
- Study completion
- 1 Dec 2021 (estimated)
- First posted
- 28 Aug 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.
Anthracyclines are associated with cardiotoxic effects. Previous studies suggest that enalapril, and or carvedilol, protect against cardiovascular effects of these drugs.
Ivabradine selectively reduces heart rate through inhibition of the cardiac pace maker IF channel, thus prolonging the duration of spontaneous depolarization in the sinus node. Additionally, ivabradine might preserve myocardial perfusion without negative inotropic effect and probably maintain cardiac contractility despite the reduction of heart rate.
Ivabradine has been shown to improve outcome in patients with heart failure and angina. The aim of this study is to evaluate whether ivabradine might prevent anthracycline-induced cardiotoxicity.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ivabradine | Active comparator | Drug: IvabradinePatients will receive ivabradine just before anthracycline chemotherapy, 5 mg per oral twice daily, until one month after the last chemotherapy session. |
| Placebo | Placebo comparator | Drug: PlaceboPatients will receive placebo just before anthracycline chemotherapy, one capsule per oral twice daily, until one month after the last chemotherapy session. |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Age 18-year-old or older;
- Cancer diagnosis;
- Chemotherapy with anthracycline;
- Written informed consent
Key exclusion criteria (7 listed)
- Chronic Kidney Disease (Creatinine clearance inferior to 30mL/min/1.73m2)
- Bradycardia (heart rate less than 60 beats per minute)
- Atrial fibrilation;
- Previous diagnosis of heart failure;
- Pregnancy;
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 |
|---|---|---|
| IvabradineIvabradine capsule | Drug | Ivabradine |
| PlaceboAlso: Placebo oral capsulePlacebo oral capsule. | Drug | Placebo |
Primary outcome
Ventricular function
Time frame: 365 days after randomization
Reduction in global longitudinal strain of at least 10% (GLS)
7 secondary outcomes
Composite endpoint of mortality or major cardiovascular outcomes
Time frame: 365 days after randomization
Left ventricular dysfunction
Time frame: 365 days after randomization
Incidence of myocardial injury
Time frame: 90 days after randomization
Incidence of myocardial injury
Time frame: 180 days after randomization
Incidence of myocardial injury
Time frame: 365 days after randomization
Diastolic dysfunction
Time frame: 365 days after randomization
Ventricular function
Time frame: 180 days after randomization
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2019.
- Derived from this study: PubMed 40357644Rizk SI, Costa IBSDS, Cruz CBBV, Pileggi B, de Almeida Andrade FT, Gonzalez TB, Bittar CS, Fukushima JT, Quintao VC, Osawa EA, Alves JBS, Fonseca SMR, Garcia DR, Pereira J, Buccheri V, Avila J, Kawahara LT, Barros CCS, Ikeoka LT, Nakada LN, Fellini M, Rocha VG, Rego EM, Hoff PMG, Filho RK, Landoni G, Hajjar LA. Randomized, Placebo-Controlled, Triple-Blind Clinical Trial of Ivabradine for the Prevention of Cardiac Dysfunction During Anthracycline-Based Cancer Therapy. J Am Heart Assoc. 2025 May 20;14(10):e039745. doi: 10.1161/JAHA.124.039745. Epub 2025 May 13.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ivabradine in people with Neoplasms and Heart Failure, run by University of Sao Paulo at 1 site in Brazil.
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 7 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 2 Apr 2019. 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 Brazil. 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.
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 Stephanie I Rizk, MD (+551138932000 ext. 3271, stephrizk@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Ventricular function (time frame: 365 days after randomization). 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 NCT03650205, which also lists 1 linked publication.
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 2 Apr 2019.