Effect of Ivabradine on Microcirculation and Cardiac Output in Septic Shock Patients

NCT05141071 | Completed Phase 2

• 1 other identifier: MD-214 -2019
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

Persistent tachycardia in sepsis or multi-organ dysfunction syndrome (MODS) is an ominous sign. This usually comes under control with judicious use of antibiotics, fluid resuscitation, sedation. Uncontrolled tachycardia in systemic inflammatory response syndrome and sepsis deprives the heart muscle of oxygen. As it progresses, insufficient heart muscle nutrition eventually leads to myocardial dysfunction. It can also present as heart failure. In acute coronary syndromes, beta blockers are used to control heart rate. However in MODS, it cannot be used due to hemodynamic instability and worsened myocardial function. Sinoatrial (SA) myocytes are the pacemaker cells in the heart. Pacemaker activity involves several ionic currents that influences spontaneous depolarization of SA node including I(f) current. The word I(f) means funny, because this current has unusual properties as compared with other currents known at the time of its discovery. It is one of the most important ionic current for regulating pacemaker activity in SA node. Ivabradine is an I(f) current inhibitor in SA node. Currently, it is the only agent shown to clinically lower heart rate with no negative inotropism or effects on conduction and contractility.so usage of Ivabradine to control tachycardia in patients with septic shock may help to improve myocardial filling and cardiac output. Marcos L.Miranda et al. found that Ivabradine was effective in reducing microvascular derangements evoked by experimental sepsis, which was accompanied by less organ dysfunction. These results suggest that ivabradine yields beneficial effects on the microcirculation of septic animals. No data found on effect of Ivabradine on the microcirculation of human. In this study the investigators will investigate the effect of Ivabradine on perfusion in capillary circulation using Cytocam video microscope, Braedius®.

Conditions

Septic Shock

Keywords

Micro-circulation; Septic shock; Cardiac output; Ivabradine

Outcome Measures

Primary Outcomes (1)

• Microvascular flow index

  absent (0), intermittent (1), sluggish (2), or normal (3)

  6 hours after administration of Ivabradine or Placebo.

Secondary Outcomes (10)

• Microvascular flow index

  Before drug administration and at 1, 12, and 24 hours thereafter.

• Total vessel density

  Before drug administration and at 1, 6,12, and 24 hours thereafter.

• Percentage of perfused vessels

  Before drug administration and at 1, 6,12, and 24 hours thereafter.

• Cardiac output

  Before drug administration and at 1, 6,12, and 24 hours thereafter.

• Heart rate

  Before drug administration and at 1, 6,12, and 24 hours thereafter.

Study Arms (2)

Ivabradine

EXPERIMENTAL

In the study group, Ivabradine(I) group; patients will receive an enteral Ivabradine (dissolved in distilled water) 5mg twice daily (every 12 hours) via a naso-gastric tube.

Drug: Ivabradine 5mg Tab

Placebo

PLACEBO COMPARATOR

the control group, Placebo (P) group; patients will receive 50 ml of saline twice daily also via a naso-gastric tube.

Drug: Placebo

Interventions

Ivabradine 5mg Tab DRUG

Ivabradine will be administrated enterally

Also known as: procoralan, ATC code: C01EB17

Ivabradine

Placebo DRUG

50 ml of saline will be administrated enterally

Also known as: 0.9% saline solution

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years.
• Patients admitted to ICU with septic shock.

You may not qualify if:

• Patients contraindicated to begin oral feeding (NPO patients).
• Patients diagnosed with arrhythmia.

Sponsors & Collaborators

• Cairo University: lead

Study Sites (1)

Kasr Alainy Hospital

Cairo, Manial, 11562, Egypt

Location

MeSH Terms

Conditions

Shock, Septic

Interventions

Ivabradine; Saline Solution

Condition Hierarchy (Ancestors)

Sepsis; Infections; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Shock

Intervention Hierarchy (Ancestors)

Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Crystalloid Solutions; Isotonic Solutions; Solutions; Pharmaceutical Preparations

Study Officials

• Amr K Abdelhakim, MD

  Cairo University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Lecturer of Anesthesia and Intensive care medicine

Study Record Dates

• First Submitted: August 12, 2021
• First Posted: December 2, 2021
• Study Start: November 25, 2021
• Primary Completion: May 25, 2022
• Study Completion: June 5, 2022
• Last Updated: September 1, 2022

Record last verified: 2022-08

Locations

EG (1)