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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT04828226
Other study ID # BECD-3-21
Secondary ID
Status Recruiting
Phase Phase 4
First received
Last updated
Start date April 27, 2021
Est. completion date May 27, 2025

Study information

Verified date November 2023
Source Insel Gruppe AG, University Hospital Bern
Contact Christian M Beilstein, MD
Phone +41 31 632 24 82
Email Christian.Beilstein@insel.ch
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


Description:

Electroconvulsive therapy (ECT) is a highly efficacious therapy for psychiatric disorders, especially major depressive disorder, bipolar disorder and catatonia resistant to psychopharmacology or drug-psychotherapy combination therapy. At therapy induction, usually a series of 10-12 ECT sessions is planned with two to three days in between sessions. Thereafter, maintenance therapy can be continued with longer session intervals thereafter to avoid relapses and to support further drug and psychotherapy treatment. Without maintenance therapy, relapses can happen in up to 80% of all patients within one year. Nowadays conducted under general anaesthesia (etomidate in the investigator's centre) and muscle relaxation (suxamethonium) to prevent adverse events, ECT can be challenging for the anaesthesiologist, as it usually leads to rapid cardiovascular changes such as sudden bradycardia due to vagal discharge, followed by sympathetic counter regulation associated with tachycardia and hypertension. For the patient, known immediate side effects are headache in about 30% and postictal confusion and delirium in up to 65%. This confusional state can lead to involuntary movements and agitation and therefore be harmful for patients and attending staff. It usually resolves within 45 minutes but nevertheless seems to be linked with adverse side effects like persistent retrograde amnesia. Identified risk factors are long seizure time and pre-existing catatonic features. Postictal delirium has been classified by Kikuchi et. al. into four categories from no delirium, mild, moderate or severe delirium. Moderate to severe delirium needing restraints or sedative medication like benzodiazepines or Propofol was present 36% of patients, which is in line with older data. The more severe forms of delirium are easily recognised in clinical practice because of the need for intervention. When including mild forms, delirium was present in 52% of all patients in the study of Kikuchi et al. In newer studies using a more sensitive tool (CAM-ICU, Confusion Assessment Method - Intensive Care Unit) to assess the presence of delirium, the rates are up to 65% at 10 minutes after ECT stimulation respectively 10 minutes after arrival in the post-anaesthesia care unit. CAM-ICU is a brief but sensitive test, which has been extensively validated in the intensive care setting. Therefore, it seems that postictal delirium is frequently underdiagnosed in clinical practice. As we know from the intensive care literature, even hypoactive forms of delirium are associated with higher complication rates and higher mortality and therefore cannot be neglected. In previous small studies, premedication with promethazine, midazolam and dexmedetomidine successfully reduced incidence of postictal delirium. Dexmedetomidine, a highly selective, relatively short acting alpha2-agonist, has been more extensively studied in the setting of ECT and has recently been able to show his potency to reduce postictal delirium by a third when given as a bolus pre-induction in a randomised controlled trial. In this prospective, randomised, placebo-controlled, triple-blind, single-centre, two-arm parallel groups superiority trial, the investigators aim to lower incidence and severity of postictal delirium and agitation using a pre-induction dose of 2 mcg/kg clonidine intravenously compared to placebo (sodium chloride). The investigators also hypothesise, that a pre-induction dose of clonidine will reduce incidence of postictal agitation, the need for sedative rescue medication and the need for short-acting antihypertensive medication. It therefore might increase patient safety and cost effectiveness without prolonging post-anaesthesia care unit stay or negatively affecting treatment efficacy.


Recruitment information / eligibility

Status Recruiting
Enrollment 130
Est. completion date May 27, 2025
Est. primary completion date April 27, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria: - 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). Exclusion Criteria: - 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.

Study Design


Intervention

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

Locations

Country Name City State
Switzerland Department of Anaesthesiology and Pain Medicine, Bern University Hospital, University of Bern Bern

Sponsors (2)

Lead Sponsor Collaborator
Insel Gruppe AG, University Hospital Bern University of Bern

Country where clinical trial is conducted

Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary 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 Incidence of mild agitation RASS +1, needing verbal command or short restraint < 1 minute post-anaesthesia care unit stay (up to 2 hours)
Secondary Incidence of severe agitation RASS > 1, needing restraint > 1 minute or rescue medication) post-anaesthesia care unit stay (up to 2 hours)
Secondary Use of rescue medication medication, dose, route post-anaesthesia care unit stay (up to 2 hours)
Secondary Duration of seizure activity seconds during procedure (estimated to be on average 10-15 minutes)
Secondary Quality of seizure activity ideal, sufficient, insufficient during procedure (estimated to be on average 10-15 minutes)
Secondary Seizure Quality Index Seizure Quality Index (Kranaster et al., Eur Arch Psychiatry Clin Neurosci 2018) ranging from 0 to 5. Higher index indicates better response to treatment. during procedure (estimated to be on average 10-15 minutes)
Secondary Need for seizure terminating medication medication, dose, route during procedure (estimated to be on average 10-15 minutes)
Secondary Total number of electroconvulsive therapy sessions number whole treatment course (12 ECT sessions, about 4 weeks)
Secondary Reason for terminating or continuing the electroconvulsive series failure, response, remission, other reason whole treatment course (12 ECT sessions, about 4 weeks)
Secondary Length of post-anaesthesia care unit stay minutes post-anaesthesia care unit stay (up to 2 hours)
Secondary Incidence of desaturation Oxygen saturation by pulse oximetry < 75%, irrespective of duration post-anaesthesia care unit stay (up to 2 hours)
Secondary Incidence of hypotension any measurement with mean arterial pressure < 55 mmHg during procedure (estimated to be on average 10-15 minutes)
Secondary Incidence of bradycardia heart rate < 50 bpm for more than 1 minute post-anaesthesia care unit stay (up to 2 hours)
Secondary Cardiovascular changes needing intervention number and type post-anaesthesia care unit stay (up to 2 hours)
Secondary Use of cardiovascular medication medication, dose, route post-anaesthesia care unit stay (up to 2 hours)
Secondary Adverse events potentially attributable to ECT diagnosis whole treatment course (12 ECT sessions, about 4 weeks)
Secondary Adverse events potentially attributable to Study Drug diagnosis whole treatment course (12 ECT sessions, about 4 weeks)
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