Clonidine to Prevent Delirium After Electroconvulsive Therapy.

NCT04828226 | Recruiting Phase 4

• 1 other identifier: BECD-3-21
• Study Type: interventional
• Target: 130
• Locations: 1 country
• Sites: 1

Brief Summary

Electroconvulsive therapy (ECT) is a highly effective treatment for some psychiatric disorders like major depressive or bipolar disorder, but may lead to agitation and delirium after the procedure in up to 65% of patients. This can have negative side effects and be dangerous for patient and attending staff. Clonidine, a central-acting alpha2-receptor agonist, is an approved antihypertensive medication with known sedative side effects. Clonidine's newer but more expensive successor, dexmedetomidine, has recently shown its potential to reduce this kind of delirium. The investigators therefore hypothesise that pre-treatment with 2 mcg/kg clonidine prior to electroconvulsive therapy will significantly reduce the incidence of postictal delirium. This potentially makes a highly efficient treatment for patients with otherwise refractory psychiatric illness safer and more accessible.

Conditions

Major Depressive Disorder; Catatonia; Bipolar Disorder; Delirium Postseizure

Keywords

Electroconvulsive Therapy; ECT; Clonidine; Postictal Delirium; Postseizure Delirium; Postictal Agitation; Postseizure Agitation; CAM-ICU; RASS

Outcome Measures

Primary Outcomes (1)

• Incidence of delirium after electroconvulsive therapy over all (twelve) ECT sessions

  The primary outcome is delirium after electroconvulsive therapy over all (twelve) ECT sessions. The presence of delirium will be assessed using Confusion Assessment Method - Intensive Care Unit (CAM-ICU). To be able to perform the test correctly, the patient must be awake enough. This will be assessed using the Richmond-Agitation-Sedation-Scale (RASS) first ranging from -5 (unarousable) to +4 (combative)

  20 minutes after muscle relaxation

Secondary Outcomes (17)

• Incidence of mild agitation

  post-anaesthesia care unit stay (up to 2 hours)

• Incidence of severe agitation

  post-anaesthesia care unit stay (up to 2 hours)

• Use of rescue medication

  post-anaesthesia care unit stay (up to 2 hours)

• Duration of seizure activity

  during procedure (estimated to be on average 10-15 minutes)

• Quality of seizure activity

  during procedure (estimated to be on average 10-15 minutes)

Study Arms (2)

Intervention

EXPERIMENTAL

The study drug (clonidine 2 mcg/kg) is diluted in 100 ml sodium chloride 0.9 % by trained post-anaesthesia care staff not involved in the study. At admission, electrocardiogram, non-invasive blood pressure and pulse oximetry is installed, a peripheral venous line established and supplemental oxygen applied. The study drug will be given intravenously over 10 minutes at least 10 minutes before induction of anaesthesia. Electroconvulsive therapy will be conducted according to hospital standard (Etomidate 0.2 mg/kg, Suxamethonium 1.0 mg/kg, isolated limb technique, THYMATRON® SYSTEM IV, Somatics Inc., Lake Bluf, Illinois, USA) adjusted to the patient's condition. Seizure quality will be assessed, prolonged seizure activity terminated with propofol 0.2 - 0.3 mg/kg. Severe agitation (Richmond Agitation and Sedation Score (RASS) \> 1) needing intervention will be treated with propofol or lorazepam. Patients will be assessed for delirium using CAM-ICU at 20 minutes after induction.

Drug: Clonidine

Control

PLACEBO COMPARATOR

The placebo will be created by diluting 1ml of sodium chloride 0.9% in 100ml of sodium chloride in a sterile manner prior to application. The container will be identically labelled as the verum. The placebo will be applied by the same team members named above via the same route (intravenously), with the same speed and the same timing. All other parts of the procedure are identical as to the procedure described above.

Drug: Placebo

Interventions

Clonidine DRUG

Clonidine 2mcg/kg Body Weight diluted in 100ml sodium chloride 0.9% compared to placebo (sodium chloride 0.9% alone) given over 10 minutes, 10 minutes prior to electroconvulsive therapy.

Also known as: Verum

Intervention

Placebo DRUG

Sodium chloride 0.9% 100ml given over 10minutes, 10 minutes prior to electroconvulsive therapy.

Control

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 and more;
• Scheduled for an elective series of ambulatory ECT sessions at the University Hospital Bern;
• Informed Consent as documented by signature (Appendix Informed Consent Form).

You may not qualify if:

• Contraindications to the study drug, e. g. known allergy or hypersensitivity, hypotension, bradycardia, higher grade atrioventricular block;
• On regular Clonidine for another indication (e.g. arterial hypertension)
• Patients undergoing emergency ECT;
• Unable to consent (incapable of judgment, next-of-kin consent necessary or under tutelage);
• Inability to follow the procedures of the study, e. g. due to language barrier;
• Previous enrolment into the current study;
• Participation in another study with investigational drug within the 30 days preceding and during the present study;
• Enrolment of the investigator, his/her family members, employees and other dependent persons.
• Women who are pregnant or breast feeding;
• Intention to become pregnant during the course of the study;
• Lack of safe contraception, defined as: Female participants of childbearing potential, not using and not willing to continue using a medically reliable method of contraception for the entire study duration (and 4 weeks thereafter), such as oral, injectable, or implantable contraceptives, or intrauterine contraceptive devices, or who are not using any other method considered sufficiently reliable by the investigator in individual cases. Female participants who are surgically sterilised / hysterectomised or post-menopausal for longer than 2 years are not considered as being of child bearing potential.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator

Study Sites (1)

Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern

Bern, 3010, Switzerland

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Major; Catatonia; Bipolar Disorder

Interventions

Clonidine; calcium D-pantothenate, L-cysteine drug combination

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Behavioral Symptoms; Behavior; Bipolar and Related Disorders

Intervention Hierarchy (Ancestors)

Imidazolines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Patrick Y Wüthrich, Prof, MD

  Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Christian M Beilstein, MD

CONTACT

+41 31 632 24 82; Christian.Beilstein@insel.ch

Patrick Y Wüthrich, Prof, MD

CONTACT

+41 31 632 24 81; Patrich.Wuethrich@insel.ch

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: After randomisation in RedCap, a study nurse otherwise not involved in the trial will store group allocation in an envelope (labelled with the patients study identifier, name and date of birth) in a closed cupboard accessible to the post-anaesthesia care team member preparing the study drug, but not the treating or assessing team. After a patient's trial completion, the envelope and its content will be destroyed. Therefore, the treating team, the patient as well as the data collecting personnel is blinded to group allocation. The bottles containing study drug or placebo are identical and are identically labelled with "Study Drug" and the patients name by the independent post-anaesthesia care member preparing the study drug before ECT sessions start. Data analysts will be blinded as well because allocation to verum or placebo is only known to the study nurse randomising patients and preparing the envelopes needed for drug preparation.
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a prospective, randomised, placebo-controlled, triple blind, single-centre, two-arm parallel groups superiority trial assessing incidence and severity of postictal delirium.

Study Record Dates

• First Submitted: March 30, 2021
• First Posted: April 1, 2021
• Study Start: April 27, 2021
• Primary Completion (Estimated): July 27, 2026
• Study Completion (Estimated): July 31, 2026
• Last Updated: August 6, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)