A Phase 4 interventional study of Ivabradine in Sepsis, Ivabradine and Hemodynamics, sponsored by Second Affiliated Hospital of Guangzhou Medical University. Recruiting at 3 sites in China. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-04-24.
Sponsored by Second Affiliated Hospital of Guangzhou Medical University · Phase 4, Interventional, and Treatment
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.
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.
2,416 studies on the registry are indexed under Sepsis; 541 are open to participants now.
This study's planned enrollment of 172 is above the median of 102 across 1,165 interventional studies indexed under Sepsis.
Browse Sepsis studies →Second Affiliated Hospital of Guangzhou Medical University is the lead sponsor of 74 studies on the registry; 53 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Contraindication
A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
CYP3A (CYP3A4) inhibitors and inducers
CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.
Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
NYHA class (heart failure)
The New York Heart Association’s four classes of how much heart failure limits physical activity.
Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Relapsed and refractory
Relapsed: the illness came back after treatment had worked. Refractory: it did not respond to treatment, or stopped responding while still on it.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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.
Standard treatment for sepsis plus enteral ivabradine.
Drug: Ivabradine
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.
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 96 hours
28-day overall mortality
Overall survival measured from randomization to death or day 28
Time frame: 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.
Time frame: 96 hours
length of ICU stay
average length of ICU stay will be compared
Time frame: 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.
Time frame: 28 days
length of in-hospital stay
average length of in-hospital stay will be compared
Time frame: 28 days
Incidence of adverse events
The incidence of adverse events will be compared between the two groups
Time frame: 96 hours
Plan to share: No
Started Jun 2023 (actual). Primary completion is estimated for Dec 2026, 42 months after the start.
Of 65 non-industry phase 4 interventional studies under Sepsis, half reached primary completion within 25 months of starting (the median), counting those still running; a quarter within 15 and three quarters within 45. This study's planned 42 months is above that.
Counting every sponsor, half of 66 studies reached it within 25 months; a quarter within 15 and three quarters within 43.
How these figures are worked out, and which studies are left out of them.
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Studies of the drug tested here: Ivabradine
Second Affiliated Hospital of Guangzhou Medical University