Effectiveness of Enteral Ivabradine Plus Standard Therapy vs Standard Therapy Alone for Heart Rate Control in Patients with Septic Shock: A Single-blind Randomized Controlled Trial

Q: What are the key findings of this study?

Enteral ivabradine plus standard therapy significantly reduced median heart rate at 96 hours compared to standard therapy alone (88 vs 110 bpm; adjusted MD -19.1 bpm, p<0.001) in septic shock.

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Septic shock with persistent tachycardia (n=234). Intervention: Enteral ivabradine plus standard therapy vs. Standard therapy alone. Primary outcome: Heart rate at 96 hours following randomization (Adjusted MD -19.1 bpm, 95% CI -22.7 to -15.5, p=<0.001).

Q: What does this research mean for the field?

Enteral ivabradine plus standard therapy significantly reduces heart rate at 96 hours without compromising mean arterial pressure or safety in patients with septic shock and persistent tachycardia. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

Q: What question did this study set out to answer?

To evaluate the efficacy and safety of enteral ivabradine for heart rate control and assess its effects on hemodynamics, organ dysfunction, and clinical outcomes in patients with septic shock.

Chackappen Aymanom; Mukesh Chand Bairwa; Ravi Kant; Barun Kumar; Nidhi Kaeley; Saumyarup Pal

doi:10.5005/jp-journals-10071-25299

October 23, 2026Indian Journal of Critical Care MedicineOpen Access

Effectiveness of Enteral Ivabradine Plus Standard Therapy vs Standard Therapy Alone for Heart Rate Control in Patients with Septic Shock: A Single-blind Randomized Controlled Trial

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Key result

Enteral ivabradine lowers heart rate by ~19 bpm at 96 hours in septic shock.

Adjusted MD -19.1 bpm
95% CI -22.7 to -15.5
P<0.001
n=234

Why the study?

Persistent tachycardia in septic shock is associated with adverse hemodynamic and clinical outcomes. The efficacy and safety of enteral ivabradine for heart rate control, hemodynamics, organ dysfunction, and clinical outcomes in these patients needed evaluation.

Does enteral ivabradine added to standard therapy reduce heart rate at 96 hours compared to standard therapy alone in adult patients with septic shock and persistent tachycardia?

Key Points

To evaluate the efficacy and safety of enteral ivabradine for heart rate control and assess its effects on hemodynamics, organ dysfunction, and clinical outcomes in patients with septic shock.
Prospective, single-center, single-blind randomized controlled trial in India (CTRI/2024/09/074220) enrolling 234 adults with septic shock and persistent tachycardia (>100 beats/min after 24 hours of resuscitation).
Participants were randomly assigned 1:1 to enteral ivabradine (5 mg titrated to 7.5 mg twice daily for up to 96 hours) plus standard therapy (n = 117) or standard therapy alone (n = 117), evaluated by intention-to-treat analysis.
At 96 hours, ivabradine significantly reduced median heart rate compared to standard therapy (88 [IQR 84–94] vs 110 [IQR 99–118] beats/min; p < 0.001; adjusted mean difference −19.1 bpm; 95% CI −22.7 to −15.5; p < 0.001).
Mean arterial pressure was higher with ivabradine at 96 hours (80 vs 78 mm Hg; p = 0.04), whereas between-group differences in serum lactate, SOFA score, noradrenaline requirements, and ICU stay duration were not statistically significant.
Fourteen-day mortality did not significantly differ between groups (23.9% in the ivabradine group vs 30.8% in controls; absolute risk reduction 6.9%; 95% CI −4.5 to 18.3; p = 0.38), and no symptomatic bradycardia occurred.

Study Design

Type

RCT (n=234)

Blinding

Single-blind (participant-blinded, investigator-blinded for statistical analysis)

Randomization

1:1 computer-generated random number sequence with sequentially numbered, opaque, sealed envelopes

Multicenter

No

Structured PICO

Does enteral ivabradine added to standard therapy reduce heart rate at 96 hours compared to standard therapy alone in adult patients with septic shock and persistent tachycardia?

P

Population

234 adult ICU patients (mean age ~43.4 years, 49.6% female) with septic shock and persistent tachycardia (>100 bpm after 24 hours of resuscitation on single-agent noradrenaline), treated for up to 96 hours and followed for 14 days.

I

Intervention

Enteral ivabradine administered via gastric tube initiated at 5 mg twice daily and titrated to 7.5 mg twice daily (if heart rate remained >100 bpm after 48 hours without bradycardia or adverse effects) for up to 96 hours, added to standard septic shock therapy.

C

Comparator

Standard therapy alone in accordance with Surviving Sepsis Campaign guidelines (source control, antimicrobial administration, fluid resuscitation, noradrenaline as primary vasopressor to maintain MAP ≥65 mm Hg, and institutional ICU sedation protocol with fentanyl, propofol, and midazolam).

O

Outcome

Heart rate reduction at 96 hours following randomization.surrogate

Main Result

Mean Difference: -19.1 (95% CI -22.7–-15.5)

Absolute Event Rate: 88% vs 110%

p-value: p=<0.001

Enteral ivabradine safely and significantly reduced heart rate and slightly improved mean arterial pressure at 96 hours in patients with septic shock and persistent tachycardia, though without a statistically significant reduction in 14-day mortality.

Limitations

Single-center, single-blind design without a matching placebo in the control group
Baseline imbalances with significantly higher SOFA score, serum lactate, and noradrenaline requirement in the ivabradine group
Lack of advanced hemodynamic monitoring, cardiac output measurements, and echocardiographic diastolic function parameters
Underpowered to detect differences in mortality or long-term clinical outcomes
Exclusion of patients requiring dual vasopressor support limits generalizability to refractory septic shock
Confounding factors influencing heart rate (pain, fever, hypoxia, anemia) were not individually controlled
Single-center design
Single-blind design (treating clinicians were unblinded)
Baseline imbalances in SOFA score, serum lactate, and noradrenaline dose between groups

Implication

Enteral ivabradine may be considered for heart rate control in septic shock; confirms hemodynamic effects but leaves mortality benefit open.

Abstract

Background and aims: Persistent tachycardia in septic shock is associated with adverse hemodynamic and clinical outcomes.This study evaluated the efficacy and safety of enteral ivabradine for heart rate control, and its effects on hemodynamic parameters, organ dysfunction and clinical outcomes in patients with septic shock.Patients and methods: This prospective, single-center, single-blind randomized controlled trial (RCT) enrolled 234 adults with septic shock and persistent tachycardia (heart rate >100 beats/min after 24 hours of guideline-directed resuscitation).Participants were randomized to receive either enteral ivabradine plus standard therapy (n = 117) or standard therapy alone (n = 117).Ivabradine was initiated at 5 mg twice daily and titrated to 7.5 mg twice daily for up to 96 hours.The primary outcome was heart rate reduction at 96 hours.Secondary outcomes included changes in mean arterial pressure (MAP), serum lactate, sequential organ failure assessment (SOFA) score, noradrenaline requirement, intensive care unit (ICU) stay duration, and 14-day mortality.Results: At 96 hours, the ivabradine group had significantly lower heart rates than the standard treatment group [median 88 [interquartile range (IQR) 84-94] vs 110 [IQR 99-118] beats/min; p < 0.001].Mean arterial pressure was higher in the intervention group at 96 hours (80 vs 78 mm Hg; p = 0.04).Although between-group differences in serum lactate, SOFA score, and noradrenaline requirement were not statistically significant, the ivabradine group demonstrated significant within-group improvement over time.Ejection fraction was stable, confirming safety.Fourteen-day mortality was 23.9% in the intervention group and 30.8% in controls (absolute risk reduction 6.9%; 95% confidence interval (CI) -4.5 to 18.3; p = 0.38).Intensive care unit stay was comparable.Conclusion: Enteral ivabradine safely lowered heart rate and improved hemodynamics in septic shock patients.No significant mortality benefit was demonstrated, although favorable hemodynamic and metabolic changes were observed during follow-up.Clinical significance: Enteral ivabradine may be a safe adjunct for heart rate control and hemodynamic stabilization in septic shock with persistent tachycardia.Clinical trial registration no: Clinical trial registry of India (CTRI/2024/09/074220).

Discussion

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Cite This Study

Aymanom et al. (2026) conducted an RCT in Septic shock with persistent tachycardia (n=234). Enteral ivabradine plus standard therapy vs. Standard therapy alone was evaluated on Heart rate at 96 hours following randomization (Adjusted MD -19.1 bpm, 95% CI -22.7 to -15.5, p=<0.001). Enteral ivabradine plus standard therapy significantly reduced median heart rate at 96 hours compared to standard therapy alone (88 vs 110 bpm; adjusted MD -19.1 bpm, p<0.001) in septic shock.

synapsesocial.com/papers/6ae682a3e432e7a5c4ef3633 https://doi.org/10.5005/jp-journals-10071-25299

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Effectiveness of Enteral Ivabradine Plus Standard Therapy vs Standard Therapy Alone for Heart Rate Control in Patients with Septic Shock: A Single-blind Randomized Controlled Trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

Effectiveness of Enteral Ivabradine Plus Standard Therapy vs Standard Therapy Alone for Heart Rate Control in Patients with Septic Shock: A Single-blind Randomized Controlled Trial

Key Points

Study Design

Structured PICO

Main Result

Limitations

Implication

Abstract

Discussion

Cite This Study

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