Prospective Evaluation Analysis and Kinetics Registry (PEAKS)

• ClinicalTrials.gov Identifier: NCT05247320
• Recruitment Status: Enrolling by invitation
• First Posted: February 18, 2022
• Last Update Posted: August 30, 2022
• Sponsor: University of Utah
• Collaborator: AltaThera Pharmaceuticals, LLC
• Information provided by (Responsible Party): Benjamin A. Steinberg, University of Utah

Study Description

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.

Condition or disease	Intervention/treatment
Atrial Arrhythmia	Drug: Sotalol Injection

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 150 participants
• Observational Model: Cohort
• Time Perspective: Other
• Official Title: Prospective Evaluation Analysis and Kinetics of IV Sotalol
• Actual Study Start Date: February 4, 2022
• Estimated Primary Completion Date: December 2023
• Estimated Study Completion Date: December 2023

Groups and Cohorts

Group/Cohort	Intervention/treatment
Prospective	Drug: Sotalol Injection; Standard of care IV sotalol infusion for atrial arrhythmias
Retrospective	Drug: Sotalol Injection; Standard of care IV sotalol infusion for atrial arrhythmias

Outcome Measures

Primary Outcome Measures :

1. Number of participants completing IV sotalol loading for atrial arrhythmias [ Time Frame: Enrollment of patient until 7 days following discharge ]
   To describe the characteristics of patients receiving treatment for atrial arrhythmias with the IV formulation of Sotalol.

Secondary Outcome Measures :

1. Number of participants with symptomatic/actionable bradycardia. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
2. Number of participants with QTc prolongation >500 ms (or 550 ms for underlying BBB). [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
3. Number of participants with recurrent AT/AF +/- RVR. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
4. Number of participants with any ventricular arrhythmia (sustained or non-sustained. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
5. Number of participants with Sudden Cardiac Death (SCD) (including aborted). [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
6. Number of participants with Hypotension Symptomatic or <=90/50. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
7. Number of participants with unplanned hospitalization prolongation. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
8. Number of participants with unplanned rehospitalization. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.
9. Number of participants with death. [ Time Frame: Infusion IV Sotalol out to 3 months. ]
   To describe the short-term safety and efficacy outcomes among patients receiving IV Sotalol for atrial arrhythmias in clinical practice.

Other Outcome Measures:

1. Sotalol levels measured at 0-30 minutes before IV dose. [ Time Frame: 0 - 30 min before IV dose ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
2. Sotalol levels measured at 0-5 minutes after end of IV infusion. [ Time Frame: 0-5 minutes after end of IV infusion. ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
3. Sotalol levels measured at 3 hours ± 5 minutes after end of IV infusion. [ Time Frame: 3 hours ± 5 minutes after end of IV infusion. ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
4. Sotalol levels measured at 0-30 minutes before first enteral dose. [ Time Frame: 0-30 minutes before first enteral dose. ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
5. Sotalol levels measured at 2-4 hours after second enteral dose. [ Time Frame: 2-4 hours after second enteral dose. ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
6. Sotalol levels measured at 2-4 hours after first enteral dose. [ Time Frame: 2-4 hours after first enteral dose. ]
   To describe the pharmacokinetics (PK) of IV Sotalol in vivo and compare it to the profiles predicted through modeling.
7. Number of participants on outpatient, mobile ECG with Bradycardia <= 40 bpm. [ Time Frame: Enrollment until 7 days following discharge ]
   Assess the use of mobile ECG to detect clinically-significant arrhythmia and changes to heart rate and QTc among these patients.
8. Number of participants on outpatient, mobile ECG with recurrent AT/AF +/- RVR. [ Time Frame: Enrollment until 7 days following discharge ]
   Assess the use of mobile ECG to detect clinically-significant arrhythmia and changes to heart rate and QTc among these patients.
9. Number of participants on outpatient, mobile ECG with QTc prolongation >500 ms (or 550 ms for underlying BBB). [ Time Frame: Enrollment until 7 days following discharge ]
   Assess the use of mobile ECG to detect clinically-significant arrhythmia and changes to heart rate and QTc among these patients.
10. Number of participants on outpatient, mobile ECG with any ventricular arrhythmia (sustained or non-sustained). [ Time Frame: Enrollment until 7 days following discharge ]
    Assess the use of mobile ECG to detect clinically-significant arrhythmia and changes to heart rate and QTc among these patients.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 100 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No
• 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.

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).

Contacts and Locations

Locations

United States, Utah

University of Utah

Salt Lake City, Utah, United States, 84112

Sponsors and Collaborators

University of Utah

AltaThera Pharmaceuticals, LLC

Investigators

• Principal Investigator: Benjamin A. Steinberg, MD, MHS; University of Utah
• Principal Investigator: Jonathan Pinccini, MD; Duke University
• Principal Investigator: Suneet Mittal, MD; Valley Health
• Principal Investigator: Parash Pokharel, MD; Geisinger Health
• Principal Investigator: Thomas F Deering, MD; Piedmont Heart Institute
• Principal Investigator: Robert Kennedy, MD; Munson Medical Center
• Principal Investigator: Michael West, MD; Presbyterian Healthcare Services
• Principal Investigator: Sergio Cossu, MD; Lehigh Valley Health Network
• Principal Investigator: Nishant Verma, MD; Northwestern
• Principal Investigator: Jonathan Silver, MD; Lahey Hospital & Medical Center
• Principal Investigator: Abhishek Deshmukh, MD; Mayo Clinic

More Information

Publications:

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.

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.

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.

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.

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.

• Responsible Party: Benjamin A. Steinberg, Associate Professor, University of Utah
• ClinicalTrials.gov Identifier: NCT05247320
• Other Study ID Numbers: 00147440
• First Posted: February 18, 2022
• Last Update Posted: August 30, 2022
• Last Verified: August 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Keywords provided by Benjamin A. Steinberg, University of Utah:

Atrial Arrhythmia; Sotalol

Additional relevant MeSH terms:

Arrhythmias, Cardiac; Heart Diseases; Cardiovascular Diseases; Pathologic Processes; Sotalol; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Physiological Effects of Drugs; Anti-Arrhythmia Agents; Sympatholytics; Autonomic Agents; Peripheral Nervous System Agents