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Effect of Heart Rate Control With Ivabradine on Hemodynamic in Patients With Sepsis

ConditionsSepsisIvabradineHemodynamicsHeart Rate Control
Trial statusRecruiting
Trial phasePhase 4
Trial typeInterventional
Biological sexAll
Age18+
SponsorSecond Affiliated Hospital of Guangzhou Medical University

About this 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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

Disqualifiers

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.

Trial design

Design model

Parallel

Treatments tested in this trial

  • Ivabradine

    Drug

    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.

Treatment groups

172 Participants
are divided into 2 treatment groups
Group A: standard treatment groupNo intervention 0 interventions
Group B: Ivabradine groupExperimental treatment 1 intervention

Trial outcomes

Primary outcomes

1

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
2

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
3

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
4

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

Secondary outcomes

1

28-day overall mortality

Overall survival measured from randomization to death or day 28

Time frame
28 days
2

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
3

length of ICU stay

average length of ICU stay will be compared

Time frame
28 days
4

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

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Second Affiliated Hospital of Guangzhou Medical University

Lead sponsor

The Third Affiliated Hospital of Guangzhou Medical University

Collaborator

Source ClinicalTrials.gov
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