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

Trial Summary

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 Dexmedetomidine generally safe for humans?

Dexmedetomidine, also known as Precedex, is generally considered safe for use in humans, but like any drug, it can have side effects. It is important to monitor for adverse drug events (unwanted effects from taking a drug), which can affect the nervous, cardiovascular, and respiratory systems. Always consult with a healthcare provider for personalized advice. ^{1 2 3 4 5}

What makes the drug Dexmedetomidine unique for treating ventricular arrhythmia?

Dexmedetomidine is unique because it is an alpha-2 adrenergic agonist that provides sedation and pain relief without causing respiratory depression, which is different from many other sedatives. It is typically used for sedation in various medical settings, and its application for ventricular arrhythmia may offer a novel approach compared to standard treatments. ^{6 7 8 9 10}

What is the purpose of this trial?

The objective of this study is to determine if there is a meaningful benefit to using the sedative medication dexmedetomidine in the acute treatment of patients with recurrent ventricular arrhythmias, known as electrical storm. This will be a multi-centre, double-blinded, placebo-controlled, randomized trial. Patients with electrical storm will be randomized to receive 48 to 72 hours of dexmedetomidine or placebo as part of their initial treatment in an intensive care unit.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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]

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]

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]

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 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]

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]

References

1. England pubmed.ncbi.nlm.nih.gov

MetaADEDB 2.0: a comprehensive database on adverse drug events. [2021]

2. England pubmed.ncbi.nlm.nih.gov

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

3. United States 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. [2021]

4. England pubmed.ncbi.nlm.nih.gov

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

5. Switzerland pubmed.ncbi.nlm.nih.gov

Drug-induced torsades de pointes: Disproportionality analysis of the United States Food and Drug Administration adverse event reporting system. [2022]

6. Japan pubmed.ncbi.nlm.nih.gov

[Feasibility and Safety of Dexmedetomidine Sedation in Transarterial Embolization for Hepatocellular Carcinoma with Hepatitis C-Related Cirrhosis]. [2015]

7. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine as an adjuvant analgesic for intractable cancer pain. [2013]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Dexmedetomidine: a guide to its use for sedation in the US. [2022]

9. France pubmed.ncbi.nlm.nih.gov

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

10. United States pubmed.ncbi.nlm.nih.gov

Dexmedetomidine related cardiac arrest in a patient with permanent pacemaker; a cautionary tale. [2013]