SepsisPhase 4NCT05882708
Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis
A Phase 4 study testing Ivabradine in people with Sepsis and Ivabradine, run by Second Affiliated Hospital of Guangzhou Medical University at 3 sites in China.
Trial summary
Sepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of adequate volume resuscitation to correct hypovolemia and vasopressor medication to correct hypotension. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Sepsis, Ivabradine, Hemodynamics
- What is being tested?
- Ivabradine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 172 participants
- Where
- 3 sitesChina
- Study dates
- 1 Jun 2023to 31 May 2027
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Adult patients aged 18 years or above.
- Being treated in an intensive care unit.
- Sepsis is diagnosed according to Sepsis-3.0 criteria, which is defined as patients requiring antimicrobial agents due to confirmed or suspected infection, acute increase in the SOFA score at least 2 points.
- Mean arterial pressure (MAP) is maintained ≥65 mmHg with adequate volume resuscitation and vasopressor therapy. Volume resuscitation is considered adequate when Central Venous Pressure (CVP) > 8mmHg, global end-diastolic volume index (GEDI) > 680ml/m2 and resting inferior vena cava (IVC) diameter > 1.5cm.
- Patients are in a relatively stable period of hemodynamics, as defined that the targe mean arterial pressure are maintained with the same dosage of vasopressors for at least 2 h.
- Sinus rhythm with heart rate ≥ 95bpm maintain for at least 2 hours but less than 72 hours.
Who cannot join
- Patients who had received ivabradine therapy or known allergy to it prior to randomization.
- Patients with severe liver dysfunction (Child-C grade).
- Patients with a history of pre-existing chronic renal failure (glomerular filtration rate less than 15 ml/min/1.73 m2), except patients treated with continuous renal replacement therapy (CRRT).
- Patients with known seizure disorder.
- Patients with any contraindication to gastrointestinal drug administration.
- Pregnant or lactating patients.
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- patients requiring the use of potent cytochrome CYP3A4 inhibitors such as antifungals of the azole-type (specifically ketoconazole and itraconazole), macrolide antibiotics (specifically clarithromycin and erythromycin) and HIV protease inhibitors (specifically nelfinavir and ritonavir).
- Patients with active bleeding;
- Patients with cardiac dysfunction caused by non-septic causes such as recent (< 2months) acute myocardial infarction, chronic cardiac dysfunction (NYHA Class Ⅳ), congenital heart disease, pericardial tamponade, severe aortic regurgitation and aortic coarctation before enrollment.
- Patients with sinoatrial block, sick sinus syndrome, atrioventricular block or heart rate dependence on pacemaker.
- Patients with refractory shock, which may be considered if one of the following conditions still exists in spite of active volume resuscitation, high doses of vasoactive drugs (VIS score >120), and other regular therapy: 1) Worsening hypotension (MAP<65mmHg); 2) Lactate persistence>5mmol/L (two times in a row with an interval of more than 30min), and a progressive upward trend; 3) Mixed venous blood oxygen saturation (SvO2) sustained <55% (more than two consecutive times, more than 30min apart), and progressive deterioration. The above conditions lasted for more than 5 hours.
- Use of beta blockers within 24 hours before enrollment.
- Pheochromocytoma patients.
- After cardiopulmonary resuscitation.
- Patients who have been enrolled in another interventional clinical study.
Trial locations and contacts
3 sites in 1 country. Contact the study team or a site near you to ask about taking part.
China3 sites, 3 recruiting
- Recruiting
the Affiliated Panyu central Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510000
Zhuandi Lin, MD, +86 13710911343, 13710911343@163.com
- Recruiting
the Second Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510000
Deliang Wen, MD, +86 18126780249, deliangw@163.com
Wei-yan Chen, MD
- Recruiting
the Third Affiliated Hospital of Guangzhou Medical University
Guangzhou, Guangdong, 510260
Zhenhui Zhang, PhD, +86 02034153246, zzhmed@126.com
Yi-chun Wang, PhD
About this study
Official title: Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis: a Prospective, Multicenter, Randomized Controlled Trial
Sepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of adequate volume resuscitation to correct hypovolemia and vasopressor medication to correct hypotension. Recently, relevant studies have shown that sustained tachycardia in sepsis was also related to high mortality, and appropriate control of heart rate could improve prognosis. Ivabradine reduces heart rate directly without a negative inotropic effect through inhibition of the If ionic current，which is absent from the traditional rate control drug (beta-blockers). This is a prospective, multicenter, randomized, open label study designed to compare ivabradine with placebo on the difference of heart rate and haemodynamics in patients with sepsis.
Read the detailed description
This study aims to enroll 172 patients with sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and sinus tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization. Patients will be randomly assigned to standard treatment group (GS) or ivabradine group (GI，standard treatment for sepsis plus enteral ivabradine). Patients in GI, with a heart rate control target of 70 to 94bpm, received ivabradine within the first 96 hours after randomization, and overall participants are followed up to 28 days. The secondary outcomes include the difference in SOFA score, incidence of serious adverse events, need for organ support, length of ICU stay, and 28-day overall mortality.
Despite recent studies are limited, this study will investigate whether HR control using ivabradine is safe, feasible, and effective, and further enhance the understanding of ivabradine in patients with sepsis.
- Conditions
- Sepsis, Ivabradine, Hemodynamics, Heart Rate Control
- Being tested
- Ivabradine
- Medical subject headings
- Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
IvabradineDrug
After randomization, the starting dose of ivabradine, 5mg, is given via the gastrointestinal tract every 12 hours. Heart rate control ranged from 70 to 94 bpm. Ivabradine was maintained until 96 hours after initiation of therapy. Beyond this period, the decision to continue ivabradine is left to the discretion of the treating intensivist. During the drug intervention period, heart rate is assessed before each dose. Ivabradine is tapered or discontinued if the heart rate is lower than the target rate; If the heart rate remains ≥95 bpm after 48 hours, the dose is increased to 7.5mg. If a heart rate of 95 or more bpm recurs after discontinuation during the intervention period, treatment with ivabradine can be resumed. Furthermore, Ivabradine is also discontinued at any time in the presence of severe liver impairment, malignant arrhythmia, cardiac conduction block, allergy, the need to take drugs with potentially harmful effects of ivabradine.
| Study group | Role | What they receive |
|---|---|---|
| standard treatment group | No intervention | Standard treatment refers to that patients received active anti-infection and treatment of primary diseases according to the 2016 International Guidelines for the Management of Sepsis and septic shock. In addition, adequate volume resuscitation and vasoactive drug support can be given to maintain MAP≥65mmHg, and life support technologies such as ventilators and CRRT were given as needed. The target of heart rate control not mentioned in the above guidelines, was not mandatory for this group of patients with sinus tachycardia, so pharmacologic intervention was not administered. |
| Ivabradine group | Experimental | Standard treatment for sepsis plus enteral ivabradine. Receives: Drug: Ivabradine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The difference of a reduction in heart rate
Heart rate is a continuous variable with repeated measurements during the first 96 hours after enrollment, the area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared.
Measured: 96 hours
The difference in MAP
MAP will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
Measured: 96 hours
The difference in CI
Cardiac index (CI) will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
Measured: 96 hours
The difference in LVEF
Left ventricular ejection fraction (LVEF)，measured by bedside ultrasound, will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
Measured: 96 hours
The difference in SVI
Stroke volume index (SVI), obtained through PiCCO, will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
Measured: 96 hours
The difference in VIS
Vasopressor requirement during the trial observation (or intervention) period ought to be recorded as vasoactive inotropic score (VIS) according to the formula. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
Measured: 96 hours
Secondary outcomes (6)
28-day overall mortality
Overall survival measured from randomization to death or day 28
Measured: 28 days
difference of the Sequential Organ Failure Assessment score
Difference of the Sequential Organ Failure Assessment (SOFA) score (0~24) at day 1, 2, 3, 4 between groups. Higher score means more illness. SOFA score include organ function measure, which can reflect the functional status of organs.
Measured: 96 hours
length of ICU stay
average length of ICU stay will be compared
Measured: 28 days
The percentage of need for organ support
the percentage of receipt of CRRT, vasopressors and mechanical ventilation. It can reflect the functional status of organs, especially renal and pulmonary.
Measured: 28 days
length of in-hospital stay
average length of in-hospital stay will be compared
Measured: 28 days
Incidence of adverse events
The incidence of adverse events will be compared between the two groups
Measured: 96 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2023
- Study start1 Jun 2023
- Primary completion31 Dec 2026 (estimated)
- Study completion31 May 2027 (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 SepsisStudies of the same condition, open and under way.
- More trials run by Second Affiliated Hospital of Guangzhou Medical UniversityThe 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
- 172 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Collaborators
- The Third Affiliated Hospital of Guangzhou Medical University
- Responsible party
- Sponsor
- Investigators
- Zhenhui Zhang, PhD, Study director, The Third Affiliated Hospital of Guangzhou Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05882708
- Sponsor's protocol ID
- 2022-LCYJ-YYDZX-02
- Status last verified
- Apr 2026
- First submitted
- 11 May 2023
- Last updated
- 24 Apr 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Zheng J, Wen D, Pan Z, Chen X, Kong T, Wen Q, Zhou H, Chen W, Zhang Z. Effect of heart rate control with ivabradine on hemodynamic in patients with sepsis: study protocol for a prospective, multicenter, randomized controlled trial. Trials. 2024 Oct 23;25(1):710. doi: 10.1186/s13063-024-08560-5.
PubMed 39443954
Study at a glance
From the registry record, last updated by the sponsor on 24 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis: a Prospective, Multicenter, Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05882708
- Acronym / sponsor ID
- 2022-LCYJ-YYDZX-02
- Conditions
- Sepsis, Ivabradine, Hemodynamics, Heart Rate Control
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 172 participants (estimated)
- Lead sponsor
- Second Affiliated Hospital of Guangzhou Medical UniversityUniversity, hospital or other
- Collaborators
- The Third Affiliated Hospital of Guangzhou Medical University
- Study start
- 1 Jun 2023 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 May 2027 (estimated)
- First posted
- 31 May 2023 (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.
Sepsis, a life-threatening syndrome, is often accompanied by tachycardia in spite of adequate volume resuscitation to correct hypovolemia and vasopressor medication to correct hypotension. Recently, relevant studies have shown that sustained tachycardia in sepsis was also related to high mortality, and appropriate control of heart rate could improve prognosis. Ivabradine reduces heart rate directly without a negative inotropic effect through inhibition of the If ionic current，which is absent from the traditional rate control drug (beta-blockers). This is a prospective, multicenter, randomized, open label study designed to compare ivabradine with placebo on the difference of heart rate and haemodynamics in patients with sepsis.
Detailed description
This study aims to enroll 172 patients with sepsis as defined by The Third International Consensus Definitions for Sepsis and Septic Shock criteria and sinus tachycardia (HR ≥ 95 bpm) despite a hemodynamic optimization. Patients will be randomly assigned to standard treatment group (GS) or ivabradine group (GI，standard treatment for sepsis plus enteral ivabradine). Patients in GI, with a heart rate control target of 70 to 94bpm, received ivabradine within the first 96 hours after randomization, and overall participants are followed up to 28 days. The secondary outcomes include the difference in SOFA score, incidence of serious adverse events, need for organ support, length of ICU stay, and 28-day overall mortality.
Despite recent studies are limited, this study will investigate whether HR control using ivabradine is safe, feasible, and effective, and further enhance the understanding of ivabradine in patients with sepsis.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| standard treatment group | No intervention | –Standard treatment refers to that patients received active anti-infection and treatment of primary diseases according to the 2016 International Guidelines for the Management of Sepsis and septic shock. In addition, adequate volume resuscitation and vasoactive drug support can be given to maintain MAP≥65mmHg, and life support technologies such as ventilators and CRRT were given as needed. The target of heart rate control not mentioned in the above guidelines, was not mandatory for this group of patients with sinus tachycardia, so pharmacologic intervention was not administered. |
| Ivabradine group | Experimental | Drug: IvabradineStandard treatment for sepsis plus enteral ivabradine. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Adult patients aged 18 years or above.
- Being treated in an intensive care unit.
- Sepsis is diagnosed according to Sepsis-3.0 criteria, which is defined as patients requiring antimicrobial agents due to confirmed or suspected infection, acute increase in the SOFA score at least 2 points.
- Mean arterial pressure (MAP) is maintained ≥65 mmHg with adequate volume resuscitation and vasopressor therapy. Volume resuscitation is considered adequate when Central Venous Pressure (CVP) > 8mmHg, global end-diastolic volume index (GEDI) > 680ml/m2 and resting inferior vena cava (IVC) diameter > 1.5cm.
- Patients are in a relatively stable period of hemodynamics, as defined that the targe mean arterial pressure are maintained with the same dosage of vasopressors for at least 2 h.
Key exclusion criteria (15 listed)
- Patients who had received ivabradine therapy or known allergy to it prior to randomization.
- Patients with severe liver dysfunction (Child-C grade).
- Patients with a history of pre-existing chronic renal failure (glomerular filtration rate less than 15 ml/min/1.73 m2), except patients treated with continuous renal replacement therapy (CRRT).
- Patients with known seizure disorder.
- Patients with any contraindication to gastrointestinal drug administration.
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 |
|---|---|---|
| IvabradineAfter randomization, the starting dose of ivabradine, 5mg, is given via the gastrointestinal tract every 12 hours. Heart rate control ranged from 70 to 94 bpm. Ivabradine was maintained until 96 hours after initiation of therapy. Beyond this period, the decision to continue ivabradine is left to the discretion of the treating intensivist. During the drug intervention period, heart rate is assessed before each dose. Ivabradine is tapered or discontinued if the heart rate is lower than the target rate; If the heart rate remains ≥95 bpm after 48 hours, the dose is increased to 7.5mg. If a heart rate of 95 or more bpm recurs after discontinuation during the intervention period, treatment with ivabradine can be resumed. Furthermore, Ivabradine is also discontinued at any time in the presence of severe liver impairment, malignant arrhythmia, cardiac conduction block, allergy, the need to take drugs with potentially harmful effects of ivabradine. | Drug | Ivabradine group |
Primary outcome
The difference of a reduction in heart rate
Time frame: 96 hours
Heart rate is a continuous variable with repeated measurements during the first 96 hours after enrollment, the area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared.
The difference in MAP
Time frame: 96 hours
MAP will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
The difference in CI
Time frame: 96 hours
Cardiac index (CI) will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
The difference in LVEF
Time frame: 96 hours
Left ventricular ejection fraction (LVEF)，measured by bedside ultrasound, will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
The difference in SVI
Time frame: 96 hours
Stroke volume index (SVI), obtained through PiCCO, will be recorded every 12 hours for each patient during the first 96 hours after enrollment. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
The difference in VIS
Time frame: 96 hours
Vasopressor requirement during the trial observation (or intervention) period ought to be recorded as vasoactive inotropic score (VIS) according to the formula. The area under the curve (AUC) relative to baseline are calculated for each group, and then difference in AUC are compared. The change in this index will be used to evaluate the hemodynamic effects of ivabradine.
6 secondary outcomes
28-day overall mortality
Time frame: 28 days
difference of the Sequential Organ Failure Assessment score
Time frame: 96 hours
length of ICU stay
Time frame: 28 days
The percentage of need for organ support
Time frame: 28 days
length of in-hospital stay
Time frame: 28 days
Incidence of adverse events
Time frame: 96 hours
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 24 Apr 2026.
- Derived from this study: PubMed 39443954Zheng J, Wen D, Pan Z, Chen X, Kong T, Wen Q, Zhou H, Chen W, Zhang Z. Effect of heart rate control with ivabradine on hemodynamic in patients with sepsis: study protocol for a prospective, multicenter, randomized controlled trial. Trials. 2024 Oct 23;25(1):710. doi: 10.1186/s13063-024-08560-5.
- 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.
Zhenhui Zhang, PhD study director
The Third Affiliated Hospital of Guangzhou Medical University
3 sites 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 in people with Sepsis and Ivabradine, run by Second Affiliated Hospital of Guangzhou Medical University at 3 sites 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 6 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: looking for participants now, as of the sponsor's last update on 24 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Zhenhui Zhang, PhD (+86 020 34153246, zhzhhicu@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The difference of a reduction in heart rate (time frame: 96 hours). The study lists 6 primary outcomes in all. 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 NCT05882708, 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 24 Apr 2026.