Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock

NCT02668432 | Terminated Phase 4 Results FDA Drug

• 1 other identifier: HSC20150864H
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Purpose/Objectives: Severe sepsis and septic shock are a common cause of new onset atrial fibrillation (NOAF) in the intensive care unit. Development of NOAF in this setting can prolong length of stay and increase mortality. Amiodarone is the most commonly used agent used in this setting to control rate and rhythm. However, limited data exist detailing appropriate dosing in this setting. The primary objective of this study is to evaluate two amiodarone dosing strategies, a full loading dose versus a partial loading dose, in patients with new-onset atrial fibrillation (AF) due to severe sepsis or septic shock to assess the mean heart rate every 6 hours after initiation of amiodarone infusion to day 7 or death. Research Design/Plan: Consecutive patients admitted to the medical or cardiac intensive care unit at University Hospital with NOAF in the setting of severe sepsis or septic shock will be screened for study inclusion. Data will be collected and stored using Microsoft Excel or Access and analyzed with JMP 12.0 and SPSS. Methods: Patients aged 18 years or older who develop new-onset atrial fibrillation in the setting of severe sepsis or septic shock and in whom the medical team deems appropriate to initiate amiodarone therapy in will be considered for study inclusion. Patients will receive intravenous (IV) and oral (PO) amiodarone, as per the standard of care. Patients will be randomized to a certain quantitative loading dose strategy; either a full loading dose (≥ 5g IV or ≥10g PO +/- 20%) or a partial loading dose (\<4g IV or \< 8g PO). Clinical Relevance: With intensive care unit length of stay (ICU LOS) and mortality being twice as high in NOAF with sepsis as compared to septic patients without NOAF, the investigators ultimately aim to identify a management strategy that may minimize this morbidity and mortality while also minimizing exposure to a drug that may cause serious adverse effects.

Conditions

New Onset Atrial Fibrillation; Severe Sepsis; Septic Shock

Outcome Measures

Primary Outcomes (1)

• Mean HR Every 6 Hours Within the First 7 Days

  Evaluate two amiodarone dosing strategies, a full loading dose versus a partial loading dose, in patients with new-onset atrial fibrillation (AF) due to severe sepsis or septic shock to assess the effect on: • Mean heart rate every 6 hours within the first 7 days following initiation of amiodarone

  7 days

Secondary Outcomes (15)

• Percentage of Time Spent Hemodynamically Unstable After Initiation of Amiodarone Infusion to Day 7 or Death

  7 days

• Percentage of Time of Conversion to Normal Sinus Rhythm

  7 days

• Percentage of Time Patients Spent in Atrial Fibrillation

  7 days

• Mean Arterial Pressure (MAP)

  7 days

• Systolic Blood Pressure (SBP)

  7 days

Study Arms (2)

Partial Load

EXPERIMENTAL

All patients will receive a 150 mg intravenous (IV) bolus dose of amiodarone, followed immediately by a continuous infusion of 1 mg/min for the first six hours, with a recommended reduction to 0.5 mg/min subsequently. Conversion from IV to oral (PO) amiodarone will occur based on patient hemodynamic stability and physician/pharmacist discretion. Patients randomized to the partial load arm will receive \<4g IV or \< 8g PO. The assigned total loading dose will include all IV and PO amiodarone administered within 7 days from initiation of amiodarone. All doses will be compared in total PO amount (accounting for 50% bioavailability of PO versus IV amiodarone).

Drug: Amiodarone

Full Load

ACTIVE COMPARATOR

All patients will receive a 150 mg intravenous (IV) bolus dose of amiodarone, followed immediately by a continuous infusion of 1 mg/min for the first six hours, with a recommended reduction to 0.5 mg/min subsequently. Conversion from IV to oral (PO) amiodarone will occur based on patient hemodynamic stability and physician/pharmacist discretion. Patients randomized to the partial load arm will receive (≥ 5g IV or ≥10g PO +/- 20%). The assigned total loading dose will include all IV and PO amiodarone administered within 7 days from initiation of amiodarone. All doses will be compared in total PO amount (accounting for 50% bioavailability of PO versus IV amiodarone).

Drug: Amiodarone

Interventions

Amiodarone DRUG

Patients will receive a 150 mg IV bolus amiodarone dose, followed by a 1 mg/min continuous infusion for six hours, then 0.5 mg/min. Conversion to PO amiodarone will be based on patient hemodynamic stability and physician/pharmacist discretion. The total loading dose will be calculated based on all IV and PO amiodarone administered within 7 days from initiation of amiodarone. All doses will be compared in total PO equivalents (accounting for 50% bioavailability of PO vs IV amiodarone). Randomization may be overridden by the attending or fellow physician if the patient's severity of illness warrants. Discontinuation of amiodarone in the full-load group will be at the discretion of the physician/pharmacists, after the pre-determined randomization loading dose has been provided.

Also known as: Cordarone, Pacerone

Full Load; Partial Load

Eligibility Criteria

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

You may qualify if:

• New onset atrial fibrillation
• Severe sepsis or septic shock (defined by ≥2 systemic inflammatory response syndrome criteria + infection)

You may not qualify if:

• Age \< 18 years
• History of atrial flutter
• History of atrial fibrillation
• QTc \>500 msec at baseline
• nd or 3rd degree AV block
• Currently receiving anti-arrhythmic therapy
• Untreated thyroid dysfunction
• Acute or chronic hepatic failure
• Other indication for antiarrhythmic therapy
• Recent cardiac surgery in last 30 days
• Pregnancy

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University Hospital

San Antonio, Texas, 78229, United States

Location

MeSH Terms

Conditions

Sepsis; Shock, Septic

Interventions

Amiodarone

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Bethany Kalich, PharmD
• Organization: University of Texas Health San Antonio

kalich@uiwtx.edu

210-883-1177

Study Officials

• Bethany A Kalich

  UT Health San Antonio

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: January 29, 2016
• Study Start: May 1, 2016
• Primary Completion: September 20, 2018
• Study Completion: September 20, 2018
• Last Updated: April 2, 2019
• Results First Posted: April 2, 2019

Record last verified: 2018-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)