Dexmedetomidine for Ventricular Arrhythmia

(SEDATE Trial)

Overseen By F. Daniel Ramirez, MD MSc

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Ottawa Heart Institute Research Corporation

Must not be taking: Dexmedetomidine, Clonidine

Disqualifiers: Refractory shock, Cardiogenic shock, Cardiac arrest, STEMI, Bradycardia, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 1 week

192 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a sedative called dexmedetomidine (also known as Precedex) can aid patients with electrical storm, a serious heart condition characterized by dangerously fast heartbeats. Participants will receive either dexmedetomidine or a placebo in the intensive care unit to determine if the medication provides any meaningful benefits. The trial is double-blind, so neither participants nor doctors will know who receives the actual medication or the placebo. Individuals who experience repeated episodes of electrical storm and are admitted to an intensive care unit might be suitable for this trial. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking treatment.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you have taken dexmedetomidine or clonidine in the 24 hours before the trial, you cannot participate.

Is there any evidence suggesting that dexmedetomidine is likely to be safe for humans?

Research shows that dexmedetomidine is usually well-tolerated as a sedative. Some studies even suggest it can lower the risk of abnormal heart rhythms. In one study, patients using dexmedetomidine had a 65% lower risk of these heart issues compared to those who didn't use it.

However, reports of side effects exist. For instance, one patient experienced a serious heart rhythm problem after using dexmedetomidine for sedation. While dexmedetomidine is often used safely, like any treatment, it can have side effects. If there are concerns, consulting a healthcare professional is always advisable. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Unlike the standard treatments for ventricular arrhythmia, which mainly focus on blocking abnormal electrical signals in the heart, dexmedetomidine offers a novel approach by potentially stabilizing heart rhythms through its sedative and calming effects on the nervous system. This unique mechanism could provide a new way to manage arrhythmias, particularly in patients who are also dealing with stress or anxiety-related triggers. Researchers are excited about dexmedetomidine because it might reduce arrhythmias without the side effects common to current antiarrhythmic drugs, such as dizziness or potential proarrhythmic effects, offering a safer option for patients.

What evidence suggests that dexmedetomidine might be an effective treatment for ventricular arrhythmia?

Research has shown that dexmedetomidine, which participants in this trial may receive, can significantly reduce the risk of abnormal heart rhythms, known as ventricular arrhythmias. In one study, patients using dexmedetomidine had a 65% lower risk of these heart issues compared to those who did not use it. Another study found that this medication reduced the occurrence of these heart rhythm problems by more than half. Medical settings often use dexmedetomidine to help reduce stress on the heart. While effective in managing heart rhythm issues, it can also cause slower heartbeats, known as bradycardia. Overall, evidence supports its effectiveness in managing heart rhythm problems. ^{2 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for adults over 18 who are in intensive care with a condition called electrical storm, where they experience repeated episodes of dangerous heart rhythms. It's not suitable for those who may have conditions that the study excludes.

Exclusion Criteria

I have had shock requiring multiple medications to maintain blood pressure.

I am experiencing severe heart failure.

Pregnancy

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

1 week

Treatment

Participants receive dexmedetomidine or placebo for 48 to 72 hours in the intensive care unit

1 week

Continuous monitoring in ICU

Weaning

Participants undergo a weaning phase from the study drug at the discretion of the treating physician

1 week

Follow-up

Participants are monitored for safety and effectiveness after treatment during the index hospitalization

2 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Dexmedetomidine

Trial Overview

The study tests if dexmedetomidine, a sedative, helps patients with electrical storm when given as part of their initial treatment. Participants will be randomly assigned to receive either dexmedetomidine or a placebo without knowing which one they're getting.

How Is the Trial Designed?

Group I: Dexmedetomidine Active Control 1 Intervention

Participants randomized to receive dexmedetomidine will be started at a dose of 0.3 mcg/kg/hr and titrated to a target dose of 1.0 mcg/kg/hr. Once the participant reaches their maximum tolerated dose (as decided by the blinded treating physician), they will continue treatment for 48 ± 6 hours. This will be followed by a weaning phase that will similarly be at the discretion of the treating physician.

Group II: Placebo Placebo Group 1 Intervention

Participants randomized to receive placebo will be started on normal saline. In similar fashion to the active comparator, participants will be titrated to their maximal tolerated dose, continue treatment for 48 ± 6 hours, and be weaned at the discretion of the blinded treating physician.

Dexmedetomidine is already approved in European Union, United States, Canada, Japan for the following indications:

Approved in European Union as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in United States as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Canada as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Approved in Japan as Precedex for:

• Sedation in intensive care settings
• Procedural sedation

Who Is Running the Clinical Trial?

Ottawa Heart Institute Research Corporation

Lead Sponsor

Trials

200

Recruited

95,800+

Published Research Related to This Trial

In a study of 30 patients with liver dysfunction undergoing percutaneous arterial chemoembolization for hepatocellular carcinoma, dexmedetomidine sedation was successfully used in all cases, demonstrating its feasibility for this procedure.

The sedation was generally safe, with only minor adverse events reported in 3 patients, and no serious complications requiring treatment, indicating that dexmedetomidine can be a reliable option for sedation in patients with liver issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. Komemushi, A., Suzuki, S., Sano, A., et al.[2015]

Dexmedetomidine is an alpha-2 adrenergic agonist that provides sedation and pain relief without causing respiratory depression, making it a safe option for patients requiring sedation.

In a case study, dexmedetomidine was effectively used as an adjuvant analgesic for a patient with cancer pain that did not respond to other treatments, highlighting its potential role in managing complex pain scenarios.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. Roberts, SB., Wozencraft, CP., Coyne, PJ., et al.[2013]

Thalidomide, while approved for a rare illness, was predominantly used off-label, raising significant safety concerns, particularly regarding venous thromboembolism (VTE) rates of 25% when combined with doxorubicin or dexamethasone.

The FDA acknowledged that the existing safety information on thalidomide did not adequately address VTE risks, leading to a delay in the approval of a supplemental New Drug Application until safety actions, including label revisions, were implemented.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A tale of two citizens: a State Attorney General and a hematologist facilitate translation of research into US Food and Drug Administration actions--a SONAR report. Chen, B., Restaino, J., Norris, L., et al.[2021]

A study analyzing over 9 million adverse event reports identified 3,807 cases of torsades de pointes (TdP), with the highest risk associated with drugs like tolazoline, levomethadyl, and ibutilide, indicating a significant safety concern for these medications.

Notably, around half of the top drugs linked to TdP were not included in the established QT drug lists, suggesting that clinicians should be vigilant about these medications and that further research is necessary to understand their potential risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug-induced torsades de pointes: Disproportionality analysis of the United States Food and Drug Administration adverse event reporting system. Wu, Z., Zhou, P., He, N., et al.[2022]

MetaADEDB 2.0 is an updated online database that now includes 744,709 drug-adverse drug event (ADE) associations, representing a 40% increase from its previous version, making it a more comprehensive resource for researchers.

The new version features a user-friendly web interface, enhancing accessibility for drug safety assessments and studies in drug discovery and development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. Yu, Z., Wu, Z., Li, W., et al.[2021]

Dexmedetomidine was safely used to sedate a pediatric patient during 12 radiation therapy sessions, demonstrating its effectiveness as a sedative and anesthetic adjuvant.

The use of dexmedetomidine resulted in smooth induction and quick recovery while causing minimal respiratory depression, highlighting its favorable safety profile in pediatric sedation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as the primary sedative agent for brain radiation therapy in a 21-month old child. Shukry, M., Ramadhyani, U.[2013]

Over a 21-year period, 1520 significant adverse drug events (ADEs) were reported, with 29% resulting in death and 15% leading to permanent disability, highlighting the serious risks associated with medication use.

The analysis revealed that 52% of these ADEs were deemed preventable, with a significant portion of preventable cases (50%) potentially avoidable through pharmacist intervention, indicating the importance of monitoring and proper prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Potential risks and prevention, Part 4: Reports of significant adverse drug events. Kelly, WN.[2019]

Intravenous dexmedetomidine is effective for sedation in mechanically ventilated patients and during procedures, reducing the need for additional sedatives like propofol or midazolam.

It is generally well tolerated, does not cause respiratory depression, and while it may lead to hypotension and bradycardia, these side effects typically resolve on their own.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. Keating, GM., Hoy, SM., Lyseng-Williamson, KA.[2022]

Dexmedetomidine is commonly used as a safe sedative during surgeries, but there are rare cases where it can lead to serious complications, such as cardiac arrest.

In this report, a 76-year-old woman experienced cardiac arrest during a pacemaker lead extraction procedure while being treated with dexmedetomidine, highlighting the need for careful monitoring in older patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. Shah, AN., Koneru, J., Nicoara, A., et al.[2013]

New guidelines require detailed QT data in drug labels to address concerns about drug-induced heart rhythm issues, which may lead to an increase in reports of serious adverse drug reactions (ADRs) like ventricular arrhythmias and sudden death.

Studies on drugs like terfenadine and cisapride generally did not show a significant risk for proarrhythmias, highlighting the need for improved reporting and classification systems to enhance the quality of ADR reports and better inform prescribing practices.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Detection and reporting of drug-induced proarrhythmias: room for improvement. Darpö, B.[2013]

Citations

1.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC9177331/

Dexmedetomidine Reduces Incidences of Ventricular ...

Patients receiving dexmedetomidine demonstrated a significant reduction of the overall incidence of ventricular arrhythmias (RR 0.35, 95% CI 0.16, 0.76).

2.

ahajournals.org

ahajournals.org/doi/10.1161/circ.144.suppl_1.9112

Abstract 9112: Dexmedetomidine Reduces Incidences of ...

Conclusions: Our study demonstrates that the dexmedetomidine reduces the risk of VA by 65% compared to control. Further prospective research is ...

3.

nature.com

nature.com/articles/s41598-024-79236-y

Effects and mechanisms of dexmedetomidine ...

These findings suggest that DEX preconditioning can reduce the incidence of ventricular arrhythmias induced by acute stress simulated by ISO.

4.

frontiersin.org

frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2024.1433841/full

Dexmedetomidine vs. propofol on arrhythmia in cardiac ...

Our findings suggested the use of DEX reduces in-hospital ventricular arrhythmias but increases bradycardia incidence compared to propofol in adult patients ...

5.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC4472529/

The Association between Peri-Operative Dexmedetomidine ...

Dexmedetomidine is commonly used after congenital heart surgery and may be associated with a decreased incidence of post-operative tachyarrhythmias.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC3682268/

Can dexmedetomidine be a safe and efficacious sedative ...

Further, our results showed that sedation with dexmedetomidine could reduce the risk of ventricular tachycardia compared with propofol and morphine. Cardiac ...

7.

fda.gov

fda.gov/files/advisory%20committees/published/PRECEDEX-Safety-and-Drug-Utilization-Review.pdf

Precedex (dexmedetomidine) Safety and Drug Utilization ...

She experienced ventricular arrhythmia and torsades de pointes 6 hours post. DEX infusion (unknown dose) for 'transient sedation.' The case ...