A prospective randomized, single blind, controlled, safety and non-inferiority study of esketamine plus propofol compared to methohexital anesthesia for electroconvulsive therapy

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Medical University Of Vienna

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Mental Disorders [F03]

Trial duration

1 Aug 2024 → ongoing

Decision date (initial)

2024-07-09

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Medizinisch-Wissenschaftlichen Fonds des Bürgermeisters der Bundeshauptstadt Wien

External identifiers

EU CT number

2024-512210-18-00

EudraCT number

2021-003676-13

ClinicalTrials.gov

NCT05655754

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Safety

To demonstrate non inferiority of esketamine plus propofol compared to methohexital anesthesia for electroconvulsive therapy in terms of depressive symptom improvement and regarding recovery time following anesthesia

Secondary objectives 6

1. To compare the total use of concomitant anesthesiological medication summed over 8 ECT session in both treatment arms
2. To compare anesthesia with esketamine plus propofol and methohexital in terms of the finally applied stimulus charge in the eighth ECT session (as proxy for seizure quality).
3. To assess the change in cognitive outcomes after ECT in both treatment arms and compare these changes between both arms
4. To assess time to reorientation summed over 8 ECT sessions and compare between treatment arms.
5. To assess the occurrence of elevations in laboratory markers of hepatic injury in both treatment arms
6. To assess the occurrence of AEs, including hypertension, arrhythmia and agitation, as well as serum markers of myocardial damage after ECT in both treatment arms

Conditions and MedDRA coding

major depression

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 8

1. male or female inpatients
2. age ≥ 18 years
3. ICD-11 diagnosis of severe uni- or bipolar depression (F32.2, F32.2, F33.2, F33.3, F31.4, F31.5)
4. Hamilton Depression Rating Scale HAMD17 ≥ 24
5. ability to understand and willingness to sign written informed consent document
6. negative urine pregnancy test in women
7. anesthesiological approval for ECT (Classification of the American Society of Anesthesiologists ASA ≤ 3)
8. antidepressant and antipsychotic medication in steady state for at least 7 days prior to first ECT treatment

Exclusion criteria 5

1. severe somatic or neurological disease (esp. current or previous history of intracranial hypertension, uncontrolled severe hypertension, bleeds or aneurysm, recent myocardial infarction)
2. current or past history of schizophrenia or schizoaffective disorder
3. clinical relevant abnormalities on a general physical examination and routine laboratory screening
4. pregnancy, breast feeding
5. known allergy to the study drugs or compounds of the latter

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. HAMD17 change between baseline and post-ECT in both treatment arms over a series of 8 ECT sessions
2. Mean recovery time over 8 ECT sessions in both treatment arms

Secondary endpoints 6

1. The total use of concomitant medication to treat postictal hypertension, tachycardia and agitation (urapidil, metoprolol and clonidin in mg, respectively) summed over 8 ECT sessions will be compared between the ketofol and the methohexital arms.
2. Ketofol anesthesia will be non-inferior to methohexital use in terms of seizure quality. The applied stimulus charge at the 8th session can be considered an indirect measure of seizure quality and duration as the stimulus charge has to be increased throughout the ECT series if seizure duration and quality are insufficient (non-inferiority margin for final stimulus charge: 20 mC).
3. We will assess the change of cognitive outcomes (8 tests including MMSE), as assessed using a comprehensive test battery before the first and after the last treatment (see methods section), in both treatment arms, and compare these changes between treatment arms.
4. We will compare the average time to reorientation (TRO) over 8 ECT sessions in both treatment arms. We hypothesize that TRO might be correlated with cognitive outcomes in both treatment arms.
5. As ketamin has a known potential of causing liver injury, laboratory markers of liver injury (ALT, AST, gamma-GT, albumin, normotest) will be monitored at baseline, at the 4th ECT session and at termination of the course.
6. We will assess changes of blood pressure and heart rate between induction of anesthesia and immediately following seizure cessation (postictal), the occurrence of agitation during recovery (assessing changes in RASS score between induction of anesthesia and recovery) and change of markers of cardiac injury (pro-BNP, troponin T, CK-MB) before, early after (0-2h) and 24h after ECT session 1, 4 and 8. These changes will be compared between treatment arms.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Medical University Of Vienna

Sponsor organisation

Medical University Of Vienna

Address

Spitalgasse 23, Alsergrund Alsergrund

City

Vienna

Postcode

1090

Country

Austria

Scientific contact point

Organisation

Medical University Of Vienna

Contact name

Department of Psychiatry and Psychotherapy, Division of General Psychiatry

Public contact point

Organisation

Medical University Of Vienna

Contact name

Department of Psychiatry and Psychotherapy, Division of General Psychiatry

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Application history

1 submissions — initial application plus substantial / non-substantial modifications