POCA: Prevention of Post-Operative Cardiac Arrhythmias

Sponsor

Jeffrey Moak (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT04234906

Collaborator

(none)

870

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

Brief Summary

Aim 1: Primary Prevention of Post-operative Cardiac Arrhythmias

To evaluate the efficacy of dexmedetomidine vs. the combination of Magnesium Sulfate and dexmedetomidine for the prevention of post-operative cardiac arrhythmias in children and young adults undergoing open heart surgical repair for congenital or acquired heart disease using cardiopulmonary bypass. Dexmedetomidine is currently being administered to almost all patients after coming off cardiopulmonary bypass and in the CICU. For this aim, the investigator will be comparing dexmedetomidine administered alone or in combination with Magnesium Sulfate.
To evaluate medication safety based on the frequency of Serious Adverse Events (SAEs) and Adverse Events (AEs)

Aim 2: Secondary treatment of those Patients that develop a clinically significant arrhythmia despite having received either Dexmedetomidine alone or Magnesium Sulfate with Dexmedetomidine at the time of cardiac surgery

To evaluate the efficacy of intravenous (IV) Amiodarone vs. IV Procainamide for the control of postoperative cardiac arrhythmias developing after the failure of Stage 1, Preventative Trial. IV amiodarone and IV procainamide are standardly used treatment agents for the treatment of postoperative cardiac arrhythmias in this setting. The investigator will be assessing the comparative effectiveness of these agents in controlling post-operative cardiac arrhythmias.
To evaluate antiarrhythmic medication safety based on the frequency of SAEs and AEs

Condition or Disease	Intervention/Treatment	Phase
Cardiac; Dysrhythmia, Postoperative Congenital Heart Surgery	Drug: Dexmedetomidine Drug: Magnesium Sulfate Drug: Amiodarone Drug: Procainamide	Phase 4

Detailed Description

Objective: Postoperative cardiac arrhythmias (POCA) are common in children undergoing congenital heart surgery using the heart-lung machine (cardiopulmonary bypass) and have been reported in 5-38% of patients. The occurrence of arrhythmias frequently delays the patient's postoperative recovery, prolongs Cardiac Intensive Care Unit (CICU) and hospital stay, increases costs for hospital care and increases postoperative morbidity and mortality.

Magnesium Sulfate has been one agent used to reduce the occurrence of postoperative arrhythmias. The investigators recently published a propensity-score matched study of the intra-operative administration of Magnesium Sulfate revealing that as many as one-third of pediatric patients at Children's National Hospital undergoing open-heart surgery using cardiopulmonary bypass have postoperative arrhythmias. The use of intraoperative Magnesium Sulfate was associated with a reduction in the occurrence of postoperative arrhythmias. However, despite the intraoperative use of Magnesium Sulfate there continued to be a fairly high residual occurrence rate of post-operative arrhythmias (total arrhythmia frequency -18%).

Dexmedetomidine has also been showed to reduce the occurrence of POCA and has become the preferred agent used for post-operative sedation and pain control. In several studies reported in the medical literature, dexmedetomidine has been found to decrease the occurrence of POCA, like Magnesium Sulfate.

In this IRB study, the investigator is proposing a clinical study to test if the investigator can further decrease the occurrence of postoperative arrhythmias. The investigator will be studying if Magnesium Sulfate administrated in conjunction with an intravenous anesthetic medication, known as dexmedetomidine, can further decrease the primary occurrence of post-operative arrhythmias. The investigator hypothesizes that the effect achieved with the simultaneous administration of Magnesium Sulfate and dexmedetomidine will be much greater than either medication used alone.

For those patients who fail preventative medical strategies and develop clinical significant post-operative arrhythmias in need of treatment, rescue arrhythmia treatment options include the use of potent anti-arrhythmic medications that can have very dramatic effects on the patient's heart rate and blood pressure (amiodarone or procainamide). Scant published data exists providing us with guidance on the comparative efficacy and safety of these agents in the postoperative cardiac surgical patient. The investigator will compare the efficacy and adverse effects of the two agents in treating clinically significant arrhythmias that occur despite trying to prevent their onset.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

870 participants

Allocation:

Randomized

Intervention Model:

Sequential Assignment

Intervention Model Description:

Two staged, prospective randomized clinical trial: Stage 1 targets prevention of post-operative arrhythmias. Stage 2 allows for re-randomization to secondary treatment for those subjects failing Stage 1, i.e. those patients that develop and require treatment of clinically significant post-operative cardiac arrhythmias with antiarrhythmic medication.Two staged, prospective randomized clinical trial:Stage 1 targets prevention of post-operative arrhythmias. Stage 2 allows for re-randomization to secondary treatment for those subjects failing Stage 1, i.e. those patients that develop and require treatment of clinically significant post-operative cardiac arrhythmias with antiarrhythmic medication.

Masking:

None (Open Label)

Masking Description:

Patients will be randomized within each participating center, not by center, into study groups: Stage 1: Group 1 - Dexmedetomidine vs. Group 2- Magnesium Sulfate + Dexmedetomidine Stage 2: If clinically significant arrhythmias in need of treatment develop, patients will be randomized to Group 1 - amiodarone vs. procainamide. Randomization will occur through a module in Redcap.

Primary Purpose:

Treatment

Official Title:

Multicenter Study for the Prevention of Post-Operative Cardiac Arrhythmias

Anticipated Study Start Date :

Jan 1, 2023

Anticipated Primary Completion Date :

Apr 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Stage 1, Group 1 - Dexmedetomidine Dexmedetomidine: 1 mcg/kg administered at end of cardiopulmonary bypass, followed by a 0.5 mcg/kg/h infusion for 72 h postoperatively or ready for extubation prior to 72 hour time period	Drug: Dexmedetomidine Dexmedetomidine: 1 mcg/kg administered over 20 min peri-intubation period, followed by a 0.5 mcg/kg/h infusion for 72 h postoperatively or ready for extubation prior to 72 hour time period Other Names: Precedex
Active Comparator: Stage 1, Group 2- Magnesium Magnesium Sulfate (50 mg/kg) bolus administered at the time of Aortic Cross Clamp Release, with continued administration for 72 hours postoperatively at a dose of 30 mg/kg/day.	Drug: Magnesium Sulfate Magnesium Sulfate (50 mg/kg) bolus administered at the time of Aortic Cross Clamp Release, with continued administration for 72 hours postoperatively at a dose of 30 mg/kg/day
Active Comparator: Stage 2, AMIODARONE AMIODARONE I V Amiodarone 2.5 mg/kg administered over 30 minutes Second 2.5 mg/kg dose if needed over 30 minutes Continuous Intravenous Infusion 10-15 mg/kg/24 hours	Drug: Amiodarone I V Amiodarone 2.5 mg/kg administered over 30 minutes Second 2.5 mg/kg dose if needed over 30 minutes Continuous Intravenous Infusion 10-15 mg/kg/24 hours
Active Comparator: Stage 2, PROCAINAMIDE PROCAINAMIDE IV Procainamide 10-15 mg/kg administered over 45 minutes Continuous Intravenous Infusion 20-50 mcg/kg/min	Drug: Procainamide IV Procainamide 10-15 mg/kg administered over 45 minutes Continuous Intravenous Infusion 20-50 mcg/kg/min Other Names: Pronestyl

Outcome Measures

Primary Outcome Measures

Incidence of Post-Operative Cardiac Arrhythmias [3 years]
The investigator will determine the incidence of cardiac arrhythmia in the two study groups (dexmedetomidine and magnesium sulfate). Statistical analysis will be performed to determine whether a statistical difference is detected between the two study groups. The occurrence of cardiac arrhythmias will be determined from continuous cardiac telemetry.

Secondary Outcome Measures

Percent of Treatment Success Following IV Amiodarone or Procainamide Administration for Post-Operative Cardiac Arrhythmias. [3 years]
The investigator will determine treatment success (as measured by the composite of complete or partial arrhythmia control) following the administration of either IV amiodarone or procainamide administration. Percent of treatment success will be determined by the composite success group divided by all given administered each anti-arrhythmic agent. Statistical analysis will be performed to determine whether a statistical difference is detected between the two study groups. Arrhythmia control will be determined from continuous cardiac telemetry.
Incidence of Adverse Effects following IV Amiodarone or Procainamide Administration [3 years]
The investigator will determine the incidence of adverse effects (hypotension, bradycardia, or low cardiac output) following the administration of either IV amiodarone or procainamide. Statistical analysis will be performed to determine whether a statistical difference is detected between the two study groups.

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A to 35 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

1. Any infant, child, adolescent, or young adult with congenital or acquired heart disease undergoing open heart surgical repair using cardiopulmonary bypass is eligible to be enrolled in this trial.
1. No age, gender or ethnic group restrictions.

Exclusion Criteria:

1. Non-cardiopulmonary bypass repair of a congenital or acquired cardiac defect.
1. Significant pre-operative arrhythmia history
1. Past history of adverse effect to any of the study medication agents

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

Jeffrey Moak

Investigators

Principal Investigator: Jeffrey Moak, Children's National Research Institute

Study Documents (Full-Text)

None provided.

More Information

Publications

Responsible Party:

Jeffrey Moak, Director, Electrophysiology and Pacing, Principle Investigator, Clinical Professor, Children's National Research Institute

ClinicalTrials.gov Identifier:

NCT04234906

Other Study ID Numbers:

Pro00013067

First Posted:

Jan 21, 2020

Last Update Posted:

Mar 15, 2022

Last Verified:

Dec 1, 2021

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Keywords provided by Jeffrey Moak, Director, Electrophysiology and Pacing, Principle Investigator, Clinical Professor, Children's National Research Institute

Magnesium Sulfate

Dexedetomidine

anti-arrhythmic medications

Additional relevant MeSH terms:

Study Results

No Results Posted as of Mar 15, 2022