Decompensated Heart FailurePhase 1/2CONSTATHENCT02236247
Control of Sinus Node Tachycardia as an Additional Therapy in Patients With Decompensated Heart Failure
A Phase 1/2 study testing ivabradine in people with Decompensated Heart Failure, run by University of Sao Paulo at 1 site in Brazil.
Trial summary
Study aims to compare the I(f) inhibitor ivabradine with placebo as strategy of heart rate control in patients with decompensated heart failure (DHF). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Decompensated Heart Failure
- 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
- 50 participants
- Where
- 1 siteBrazil
- Study dates
- May 2013to Aug 2017
- Phase
- Phase 1/2
- 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 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Sinus node rhythm
- HR> 80 bpm
- Hospitalization for DHF
- Ejection fraction ≤ 40%
- Sign informed consent
Who cannot join
- Systolic blood pressure <85 mmHg
- Signs of hypoperfusion
- Dobutamine>15 mcg/Kg/min
- Acute myocarditis
- Primary valvular disease requiring surgery
- Stroke in the last three months
Show all 22Show fewer
- Hypertrophic or restrictive cardiomyopathy
- Sinus node disease
- Atrial fibrillation or flutter
- Second or third degree atrio-ventricular blockade
- Long QT syndrome
- Severe pulmonary disease
- Pulmonary embolism in the last three months
- Need for invasive ventilatory support
- Septicemia or septic shock
- Hepatic failure
- Creatinine > 2.5 mg/dL
- Hemodialysis
- Advanced malignancy
- Pregnancy or lactation
- Immunosuppressive therapy
- Use of cytochrome P450 inhibitors
Trial locations and contacts
1 site in 1 country.
Brazil1 site, 1 recruiting
- Recruiting
Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
São Paulo, São Paulo, 05403-900
Marco S Alves, MD, +55 11 981431512, marco.alves@incor.usp.br
Edimar A Bocchi, MD-PHD, +55 11 2661-5419, edimar.bocchi@incor.usp.br
About this study
Official title: Heart Rate Control as an Additional Therapeutic Strategy in Patients With Decompensated Heart Failure: a Prospective, Randomized, Double-blinded, Placebo-controlled Study.
Study aims to compare the I(f) inhibitor ivabradine with placebo as strategy of heart rate control in patients with decompensated heart failure (DHF).
Read the detailed description
Sympathetic hyperactivity and consequent increase in heart rate (HR) are physiological responses to low cardiac output in patients with decompensated heart failure (DHF). However, elevated HR may become inappropriate in these patients, increasing myocardial oxygen demand and decreasing diastolic filling time and might lead to hemodynamic deterioration, ventricular dysfunction (tachycardiomyopathy) and clinical deterioration.
Studies show the elevated HR is a predictor of poor prognosis in DHF. Subanalyses of large clinical trials using beta blockers (BBs) demonstrate the adequate control of HR correlates with a better outcome in patients with stable chronic heart failure (HF). However, use of BBs in patients with DHF is limited due to negative inotropic and hypotensive effects of these drugs.
As alternative to BBs, ivabradine has shown to increase survival of patients with chronic stable systolic HF. Compared to BBs, ivabradine has the advantage of "pure" negative chronotropic effect, no effect on myocardial contractility or peripheral vascular resistance. Despite the inhibition of I (f) has been validated as a therapeutic option in patients with stable HF, there are no studies available on this strategy in patients with DHF.
We hypothesized that HR control by ivabradine might improve clinical, hemodynamic and neurohormonal parameters in patients with DHF. The aim of this study was to evaluate the efficacy of HR control with ivabradine in patients with DHF.
- Conditions
- Decompensated Heart Failure
- Being tested
- ivabradine, Placebo
- Keywords
- ivabradine, heart rate, 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.
ivabradineDrug
Also called procoralan
5 mg oral twice daily
PlaceboDrug
A placebo pill (identical to ivabradine) will be administered twice daily
| Study group | Role | What they receive |
|---|---|---|
| ivabradine | Experimental | I(f) inhibitor, heart rate controller Receives: Drug: ivabradine |
| placebo | Placebo comparator | placebo pill will be administered orally twice daily Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change from baseline heart rate
Heart rate will be assessed at morning, after 30 minutes of rest, recorded by electrocardiogram.
Measured: Baseline, day 5 after intervention
Secondary outcomes (6)
Change from baseline blood pressure
Blood pressure will be measured at morning by electronic cuff
Measured: Baseline, day 5 after intervention
Change from baseline ejection fraction
Ejection fraction will be measured by echocardiography using Simpson´s rule
Measured: Baseline, day 5 after intervention
Change from baseline stroke volume
Stroke volume will be measured by echocardiography using Doppler velocity-time integral technique.
Measured: Baseline, day 5 after intervention
Change from baseline creatinine
Serum creatinine will be measured
Measured: Baseline, day 5 after intervention
Change from baseline brain natriuretic peptide
Serum brain natriuretic peptide will be measured
Measured: Baseline, day 5 after intervention
Clinical
Time of survival and free of readmission
Measured: Up to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2014 (estimated)
- Study startMay 2013
- Primary completionJan 2017 (estimated)
- Study completionAug 2017 (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 Decompensated Heart FailureStudies 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 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Sao Paulo
- Sponsor type
- University, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Responsible party
- Principal investigator, Marco Stephan Lofrano Alves, University of Sao Paulo
- Investigators
- Edimar A Bocchi, MD-PHD, Study chair, Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02236247
- Sponsor's protocol ID
- CAAE:09145612.8.0000.0068
- Other IDs
- 2012/06163-6
- Acronym
- CONSTATHE
- Status last verified
- Dec 2016
- First submitted
- 2 Sep 2014
- Last updated
- 2 Jan 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Lofrano-Alves MS, Issa VS, Biselli B, Chizzola P, Ayub-Ferreira SM, Bocchi EA. Control of sinus tachycardia as an additional therapy in patients with decompensated heart failure (CONSTATHE-DHF): A randomized, double-blind, placebo-controlled trial. J Heart Lung Transplant. 2016 Oct;35(10):1260-1264. doi: 10.1016/j.healun.2016.06.005. Epub 2016 Jun 7. No abstract available.
PubMed 27469019
Study at a glance
From the registry record, last updated by the sponsor on 2 Jan 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Heart Rate Control as an Additional Therapeutic Strategy in Patients With Decompensated Heart Failure: a Prospective, Randomized, Double-blinded, Placebo-controlled Study.
- ClinicalTrials.gov ID
- NCT02236247
- Acronym / sponsor ID
- CONSTATHE / CAAE:09145612.8.0000.0068
- Conditions
- Decompensated Heart Failure
- Keywords
- ivabradine, heart rate, heart failure
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- University of Sao PauloUniversity, hospital or other
- Collaborators
- Fundação de Amparo à Pesquisa do Estado de São Paulo
- Study start
- May 2013
- Primary completion
- Jan 2017 (estimated)
- Study completion
- Aug 2017 (estimated)
- First posted
- 10 Sep 2014 (estimated)
- 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.
Study aims to compare the I(f) inhibitor ivabradine with placebo as strategy of heart rate control in patients with decompensated heart failure (DHF).
Detailed description
Sympathetic hyperactivity and consequent increase in heart rate (HR) are physiological responses to low cardiac output in patients with decompensated heart failure (DHF). However, elevated HR may become inappropriate in these patients, increasing myocardial oxygen demand and decreasing diastolic filling time and might lead to hemodynamic deterioration, ventricular dysfunction (tachycardiomyopathy) and clinical deterioration.
Studies show the elevated HR is a predictor of poor prognosis in DHF. Subanalyses of large clinical trials using beta blockers (BBs) demonstrate the adequate control of HR correlates with a better outcome in patients with stable chronic heart failure (HF). However, use of BBs in patients with DHF is limited due to negative inotropic and hypotensive effects of these drugs.
As alternative to BBs, ivabradine has shown to increase survival of patients with chronic stable systolic HF. Compared to BBs, ivabradine has the advantage of "pure" negative chronotropic effect, no effect on myocardial contractility or peripheral vascular resistance. Despite the inhibition of I (f) has been validated as a therapeutic option in patients with stable HF, there are no studies available on this strategy in patients with DHF.
We hypothesized that HR control by ivabradine might improve clinical, hemodynamic and neurohormonal parameters in patients with DHF. The aim of this study was to evaluate the efficacy of HR control with ivabradine in patients with DHF.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ivabradine | Experimental | Drug: ivabradineI(f) inhibitor, heart rate controller |
| placebo | Placebo comparator | Drug: Placeboplacebo pill will be administered orally twice daily |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Sinus node rhythm
- HR> 80 bpm
- Hospitalization for DHF
- Ejection fraction ≤ 40%
- Sign informed consent
Key exclusion criteria (22 listed)
- Systolic blood pressure <85 mmHg
- Signs of hypoperfusion
- Dobutamine>15 mcg/Kg/min
- Acute myocarditis
- Primary valvular disease requiring surgery
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 |
|---|---|---|
| ivabradineAlso: procoralan5 mg oral twice daily | Drug | ivabradine |
| PlaceboA placebo pill (identical to ivabradine) will be administered twice daily | Drug | placebo |
Primary outcome
Change from baseline heart rate
Time frame: Baseline, day 5 after intervention
Heart rate will be assessed at morning, after 30 minutes of rest, recorded by electrocardiogram.
6 secondary outcomes
Change from baseline blood pressure
Time frame: Baseline, day 5 after intervention
Change from baseline ejection fraction
Time frame: Baseline, day 5 after intervention
Change from baseline stroke volume
Time frame: Baseline, day 5 after intervention
Change from baseline creatinine
Time frame: Baseline, day 5 after intervention
Change from baseline brain natriuretic peptide
Time frame: Baseline, day 5 after intervention
Clinical
Time frame: Up to 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jan 2017.
- Results publication: PubMed 27469019Lofrano-Alves MS, Issa VS, Biselli B, Chizzola P, Ayub-Ferreira SM, Bocchi EA. Control of sinus tachycardia as an additional therapy in patients with decompensated heart failure (CONSTATHE-DHF): A randomized, double-blind, placebo-controlled trial. J Heart Lung Transplant. 2016 Oct;35(10):1260-1264. doi: 10.1016/j.healun.2016.06.005. Epub 2016 Jun 7. No abstract available.
- Related InfoLink provided by the sponsor.
- 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.
Edimar A Bocchi, MD-PHD study chair
Heart Failure Unit, Heart Institute, University of Sao Paulo Medical School
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing ivabradine in people with Decompensated 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 5 inclusion and 22 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 Jan 2017. 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.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Contact Marco S. Alves, MD (+55 11 981431512, marco.alves@incor.usp.br), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change from baseline heart rate (time frame: Baseline, day 5 after intervention). 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 NCT02236247, 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 Jan 2017.