Clinical trial NCT05247320: Prospective Evaluation Analysis and Kinetics Registry
Official title: Prospective Evaluation Analysis and Kinetics of IV Sotalol
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Atrial Arrhythmia
Keywords: Atrial Arrhythmia
Sotalol
Lead sponsor: University of Utah
Sponsor class: OTHER
Collaborators: name: AltaThera Pharmaceuticals, LLC
First posted: 2022-02-18
Enrollment: 167
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: OTHER
Sampling method: NON_PROBABILITY_SAMPLE
Study population: This registry study will enroll adult patients 18 years and older electively treated for atrial arrhythmia with standard of care IV sotalol (initiation or dose escalation). During their elective hospitalization the patient is not planned to receive any other intervention. The registry allows retrospective and prospective enrollment. Patients will be excluded if they are undergoing treatment for active concomitant ventricular arrhythmias, intolerant to class III antiarrhythmic therapy, not meeting standard criteria to receive elective IV sotalol, or if key data elements not available (retrospective enrolled patients only). Approximately 150 patients will be enrolled and for about 20 patients PK/PD data will be collected.

Brief summary: In a cohort of patients electively treated for atrial arrhythmia with IV sotalol (initiation or dose escalation), this study will describe patient characteristics, short-term safety and efficacy, electrocardiographic monitoring, and PK and PD parameters (in a subset) associated with IV dosing approach.

Detailed description: Antiarrhythmic drug therapy plays a vital role in the achievement of rhythm control in patients with atrial arrhythmias. Class III antiarrhythmic drugs are frequently used in these patients. However, these drugs are associated with a nontrivial risk of QT interval prolongation and associated risk of life-threatening ventricular arrhythmias. In this setting, initiation and dose titration of these drugs is often performed on an inpatient basis for the first five oral doses, typically requiring hospitalization for two days or longer.

The availability of sotalol in intravenous (IV) form, recently approved for initiation or dose increase among patients with atrial arrhythmias, affords an opportunity to shorten hospitalization for these patients. This approach was approved based on translational science research that used computer-based simulation modeling to predict sotalol concentrations. There remain knowledge gaps regarding the use of IV sotalol in these patients, specifically around real-world outcomes, as well as pharmacodynamic and pharmacokinetic profiles in patients. The purpose of this registry is to collect data among patients and centers using IV sotalol loading for initiation or dose titration in the treatment of atrial arrhythmias, in order to fill the above knowledge gaps.

Eligibility criteria: Inclusion Criteria:

1. Adults age 18 years and older
2. Eligible for the use of elective intravenous sotalol loading to treat atrial arrhythmias, per the treating clinician
3. IV sotalol infusion started for the treatment of atrial arrhythmias, in the setting of initiation or dose titration of chronic sotalol therapy
4. Elective hospital admission primarily for loading with intravenous sotalol with/without cardioversion, with no other planned therapy or procedures

Exclusion Criteria:

1. Study materials not available in the subject's preferred language.
2. Patients undergoing treatment for active concomitant ventricular arrhythmias
3. Standard exclusions for elective sotalol use (at the time of initiation):

   * Heart rate \< 40 bpm or 2nd/3rd degree AV block without pacemaker
   * QTc ≥ 450 in absence of bundle branch block (≥ 500 in the presence of a bundle branch block)
   * Severe left ventricular hypertrophy (thickness \>1.5 cm)
4. Patients who were previously intolerant to antiarrhythmic class III therapy
5. Patients missing key data elements in their electronic health record (for retrospective subjects only).

Primary outcomes:
measure: Number of participants completing IV sotalol loading for atrial arrhythmias
timeFrame: Enrollment of patient until 7 days following discharge
Secondary outcomes:
measure: Number of participants with symptomatic/actionable bradycardia.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with QTc prolongation >500 ms (or 550 ms for underlying BBB).
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with recurrent AT/AF +/- RVR.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with any ventricular arrhythmia (sustained or non-sustained.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with Sudden Cardiac Death (SCD) (including aborted).
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with Hypotension Symptomatic or <=90/50.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with unplanned hospitalization prolongation.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with unplanned rehospitalization.
timeFrame: Infusion IV Sotalol out to 3 months.
measure: Number of participants with death.
timeFrame: Infusion IV Sotalol out to 3 months.
Other outcomes:
measure: Sotalol levels measured at 0-30 minutes before IV dose.
timeFrame: 0 - 30 min before IV dose
measure: Sotalol levels measured at 0-5 minutes after end of IV infusion.
timeFrame: 0-5 minutes after end of IV infusion.
measure: Sotalol levels measured at 3 hours ± 5 minutes after end of IV infusion.
timeFrame: 3 hours ± 5 minutes after end of IV infusion.
measure: Sotalol levels measured at 0-30 minutes before first enteral dose.
timeFrame: 0-30 minutes before first enteral dose.
measure: Sotalol levels measured at 2-4 hours after second enteral dose.
timeFrame: 2-4 hours after second enteral dose.
measure: Sotalol levels measured at 2-4 hours after first enteral dose.
timeFrame: 2-4 hours after first enteral dose.
measure: Number of participants on outpatient, mobile ECG with Bradycardia <= 40 bpm.
timeFrame: Enrollment until 7 days following discharge
measure: Number of participants on outpatient, mobile ECG with recurrent AT/AF +/- RVR.
timeFrame: Enrollment until 7 days following discharge
measure: Number of participants on outpatient, mobile ECG with QTc prolongation >500 ms (or 550 ms for underlying BBB).
timeFrame: Enrollment until 7 days following discharge
measure: Number of participants on outpatient, mobile ECG with any ventricular arrhythmia (sustained or non-sustained).
timeFrame: Enrollment until 7 days following discharge
Locations:
city: Salt Lake City
country: United States
facility: University of Utah
state: Utah
Study officials:
affiliation: University of Utah
name: Benjamin A. Steinberg, MD, MHS
role: PRINCIPAL_INVESTIGATOR
affiliation: Duke University
name: Jonathan Pinccini, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Valley Health
name: Suneet Mittal, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Geisinger Health
name: Parash Pokharel, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Piedmont Heart Institute
name: Thomas F Deering, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Munson Medical Center
name: Robert Kennedy, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Presbyterian Healthcare Services
name: Michael West, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lehigh Valley Health Network
name: Sergio Cossu, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Northwestern University
name: Nishant Verma, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Lahey Hospital & Medical Center
name: Jonathan Silver, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Mayo Clinic
name: Abhishek Deshmukh, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Somberg JC, Vinks AA, Dong M, Molnar J. Model-Informed Development of Sotalol Loading and Dose Escalation Employing an Intravenous Infusion. Cardiol Res. 2020 Oct;11(5):294-304. doi: 10.14740/cr1143. Epub 2020 Aug 7.
citation: Samanta R, Thiagalingam A, Turner C, Lakkireddy DJ, Kovoor P. The Use of Intravenous Sotalol in Cardiac Arrhythmias. Heart Lung Circ. 2018 Nov;27(11):1318-1326. doi: 10.1016/j.hlc.2018.03.017. Epub 2018 Mar 29.
citation: Somberg JC, Preston RA, Ranade V, Molnar J. QT prolongation and serum sotalol concentration are highly correlated following intravenous and oral sotalol. Cardiology. 2010;116(3):219-25. doi: 10.1159/000316050. Epub 2010 Aug 7.
citation: Von Bergen NH, Beshish AG, Maginot KR. Outpatient intravenous sotalol load to replace 3-day admission oral sotalol load. HeartRhythm Case Rep. 2019 Apr 24;5(7):382-383. doi: 10.1016/j.hrcr.2019.04.005. eCollection 2019 Jul. No abstract available.
citation: Etheridge SP, Asaki SY. An Exciting New Tool in the Electrophysiologist's Toolbox, Intravenous Sotalol: Faster, Safer, Better? JACC Clin Electrophysiol. 2020 Apr;6(4):433-435. doi: 10.1016/j.jacep.2019.12.016. No abstract available.