A Phase II Feasibility study to determine the efficacy and dose-response of a single enteral dose of Ivabradine to reduce participant heart rate in patients admitted to the intensive care unit with sepsis and sinus tachycardia

Ivabradine in Sepsis for Heart Rate, Benefits and Disadvantages trial (IS-HR-BAD)

Status

Recruiting

Phases

Phase 2

Study type

Interventional

Source

ANZCTR

Registry ID

ACTRN12616000940471

Acronym

IS-HR-BAD

Enrollment

Registered

2016-07-15

Start date

2016-03-02

Completion date

2017-01-31

Last updated

2020-01-13

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

None listed

Brief summary

Severe infection (sepsis) represents a common reason for admission to the ICU, often involving older people with multiple medical problems. These patients often have a prolonged hospital stay, complicated by multi-organ dysfunction leading to greater morbidity and mortality. Typically, patients have a high cardiac output, low resistance circulation, with rapid heart rates and low blood pressures requiring infusions of medications to increase blood pressure. There is an emerging body of evidence that elevated heart rates in sepsis contributes to morbidity in some people and can cause numerous complications including myocardial infarction, stress cardiomyopathy, immunosuppression and insulin resistance. Elevated heart rates may limit the time for the heart to fill between contractions, and at high rates may actually reduce the cardiac output. Controlling heart rate could therefore be beneficial. While the drug class beta-blockers are traditionally used, they have the potential to reduce blood pressure which may worsen the clinical state. Ivabradine is currently used in heart failure patients to prevent elevated heart rates, and acts via a novel receptor to reduce heart rates without impacting on contractility. The use of ivabradine in the septic population is highly novel and previously untested. This study aims to evaluate if a single dose of ivabradine is effective at reducing heart rate in septic patients, without escalation of ICU supports.

Interventions

Single dose enteral ivabradine (initially 5mg, however dose response will be reviewed after first 5 patients and dose may be increased to 10mg if inadequate response). Administered via oral/ nasogastric route. Dose will be administered under the supervision of study staff to ensure adherence.

Study design

Allocation

Non-randomised trial

Intervention model

Single group

Primary purpose

Treatment

Masking

Open (masking not used)

Eligibility

Sex/Gender

All

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Age greater than or equal to 18 years of age; 2. Presumed diagnosis of sepsis on intravenous antibiotics; 3. A heart rate of >100/min in sinus rhythm; 4. The requirement for vasopressor infusion to maintain a mean arterial pressure > 65mmHg despite adequate fluid resuscitation (defined by a central venous pressure > 8mmHg); 5. Informed consent is obtained from the patient or surrogate decision maker; 6. The patient is anticipated to require ICU care beyond the next calendar day; and 7. Presence of an indwelling urinary catheter (IDC) and arterial line

Exclusion criteria

1. Pacemaker in situ; or 2. Use of a beta blocker within the last 48 hours; or 3. History of rhythm disturbance or bradycardia; or 4. Concurrent use of inhibitors of CYP3A4 (macrolide antibiotics, azole antifungals) that interact with the metabolism of ivabradine; or 5. Inability to administer enteral medication; or 6. Severe hepatic dysfunction – defined as an AST or ALT > 5 x upper limit of normal (ULN), or and AST or ALT > 3 x ULN with an associated total bilirubin > 2 x ULN; or 7. Pregnancy; or 8. Breast-feeding mothers; or 9. Inability to complete the monitoring period in ICU following ivabradine administration; or 10. Patient not expected to survive next 24-48 hours and/or clinician not committed to ongoing life support

Outcome results