Trial Outcomes & Findings for Use of Amiodarone in Atrial Fibrillation Associated With Severe Sepsis or Septic Shock (NCT NCT02668432)

NCT ID: NCT02668432

Last Updated: 2019-04-02

Results Overview

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

• Recruitment status: TERMINATED
• Study phase: PHASE4
• Target enrollment: 9 participants
• Primary outcome timeframe: 7 days
• Results posted on: 2019-04-02

Participant Flow

Participant milestones

Measure	Partial Load 150 mg intravenous (IV) bolus dose of amiodarone, followed immediately by continuous infusion 1 mg/min for 6 hours, with a 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 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). Amiodarone: 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	Full Load 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). Amiodarone: 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
Overall Study STARTED	5	4
Overall Study COMPLETED	5	4
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Partial Load n=5 Participants 150 mg intravenous (IV) bolus dose of amiodarone, followed by continuous infusion of 1 mg/min for 6 hours, with recommended reduction to 0.5 mg/min. 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). Amiodarone: 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	Full Load n=4 Participants 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). Amiodarone: 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	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	3 Participants n=7 Participants	5 Participants n=5 Participants
Age, Categorical >=65 years	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Age, Continuous	69.21 Years STANDARD_DEVIATION 16.5 • n=5 Participants	54.8 Years STANDARD_DEVIATION 10.27 • n=7 Participants	62 Years STANDARD_DEVIATION 13.38 • n=5 Participants
Sex: Female, Male Female	2 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	4 Participants n=7 Participants	7 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Region of Enrollment United States	5 participants n=5 Participants	4 participants n=7 Participants	9 participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Mean HR Every 6 Hours Within the First 7 Days Average heart rate measured every 6 hours	115 Beats per minute Standard Error 16	122 Beats per minute Standard Error 20
Mean HR Every 6 Hours Within the First 7 Days Average heart rate measured at 7 days	71 Beats per minute Standard Error 8	94.5 Beats per minute Standard Error 9.5

SECONDARY outcome

Timeframe: 7 days

Hemodynamic instability: 1. SBP <90 mmHg OR MAP < 70 mmHg AND HR ≥ 120 bp for ≥ 2 hours OR 2. HR ≥ 120 for ≥ 2 hours OR 3. Fluid boluses ± vasopressors or dobutamine. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time Spent Hemodynamically Unstable After Initiation of Amiodarone Infusion to Day 7 or Death	39 percentage of time	11 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time patients spent with conversion from atrial fibrillation to normal sinus rhythm. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time of Conversion to Normal Sinus Rhythm	100 percentage of time	100 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time in atrial fibrillation vs normal sinus rhythm or other during a 7 day period. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time Patients Spent in Atrial Fibrillation	82 percentage of time	65 percentage of time

SECONDARY outcome

Timeframe: 7 days

Mean arterial pressure (MAP) measured over 7 days

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Mean Arterial Pressure (MAP)	64 mmHg Interval 60.0 to 73.0	75 mmHg Interval 17.0 to 89.0

SECONDARY outcome

Timeframe: 7 days

Systolic blood pressure (SBP) measured over 7 days

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Systolic Blood Pressure (SBP)	108 mmHg Interval 89.0 to 114.0	124 mmHg Interval 99.0 to 135.0

SECONDARY outcome

Timeframe: 7 days

Heart rate (HR) measured over 7 days

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Heart Rate (HR)	70 Beats per minute Interval 66.0 to 80.0	85 Beats per minute Interval 78.0 to 110.0

SECONDARY outcome

Timeframe: 7 days

Percentage time of Use of the vasopressor Norepinephrine in addition to the amiodarone. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=5 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage Time of Vasopressor Norepinephrine Use	80 percentage of time	75 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage time of use of the vasopressor Vasopressin in addition to amiodarone. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage Time of Vasopressor Vasopressin Use	40 percentage of time	25 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time of use of the vasopressor Phenylephrine in addition to amiodarone. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time of Vasopressor Phenylephrine Use	0 percentage of time	50 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time of use of a corticosteroid for treatment in addition to amiodarone use. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time of Corticosteroid Use	20 percentage of time	25 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time of use of Dobutamine in addition to amiodarone intervention. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time of Dobutamine Use	0 percentage of time	0 percentage of time

SECONDARY outcome

Timeframe: 7 days

Percentage of time of Additional medications used to control heart rate in addition to amiodarone. The reported data represents a cumulative percentage of time for the entire group of participants.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Percentage of Time of Concomitant Rate Control Medication Use	20 percentage of time	75 percentage of time

SECONDARY outcome

Timeframe: 7 days

Population: Outcome measure data were not collected or analyzed for this outcome, study terminated early due to lack of funding and due to Investigator leaving institution

Use of additional medications used with amiodarone to control heart rhythm.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 28 days

Survival to 28 days post initiation of treatment.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
28-day Mortality	4 participants	1 participants

SECONDARY outcome

Timeframe: 28 days

Number of days spent in intensive care unit after admission.

Outcome measures

Measure	Partial Load n=5 Participants \< 10g oral loading dose of amiodarone	Full Load n=4 Participants 10 g (+/- 20%) oral loading dose of amiodarone
Intensive Care Unit Length of Stay (ICU LOS)	6.5 days Interval 3.5 to 14.75	6 days Interval 5.0 to 28.0

Adverse Events

Partial Load

Serious events: 0 serious events

Other events: 0 other events

Deaths: 4 deaths

Full Load

Serious events: 0 serious events

Other events: 0 other events

Deaths: 1 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Bethany Kalich, PharmD

University of Texas Health San Antonio

Phone: 210-883-1177

Email: kalich@uiwtx.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place