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Trial record 11 of 860 for:    Ketamine

ECT With Ketamine Anesthesia vs High Intensity Ketamine With ECT Rescue for Treatment-Resistant Depression

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ClinicalTrials.gov Identifier: NCT03272698
Recruitment Status : Recruiting
First Posted : September 5, 2017
Last Update Posted : April 19, 2019
Sponsor:
Collaborator:
Royal University Hospital Foundation
Information provided by (Responsible Party):
Jonathan Gamble, University of Saskatchewan

Tracking Information
First Submitted Date  ICMJE August 28, 2017
First Posted Date  ICMJE September 5, 2017
Last Update Posted Date April 19, 2019
Actual Study Start Date  ICMJE September 1, 2017
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
Number of treatments required to reach disease remission [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments, assessed up to 4 weeks ]
The primary outcome is number of treatments required to reach disease remission, as defined by a reduction of MADRS score to under 10
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03272698 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 30, 2018)
  • Rate of rescue ECT in the HIKER arm [ Time Frame: From date of randomization up to 6 days ]
    Percent of patients in the HIKER arm who do not achieve a 25% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) after the third treatment.
  • Suicidal ideation [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Suicidal ideation as measured by the Columbia Suicide Severity Rating Scale
  • Cognitive Impairment [ Time Frame: MMSE will be assessed at baseline, final treatment, and 30 day post-treatment follow-up ]
    Cognitive Impairment as measured by Mini-Mental State Exam (MMSE)
  • Self- and clinician rated improvement [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Patients will rate their condition on the patient-rated clinical global impression - improvement scale (PGI-I)
  • Patient satisfaction with treatment [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Satisfaction with treatment will be assessed by the 2-item treatment satisfaction questionnaire for medication-version II (TSQM-GS-II).
Original Secondary Outcome Measures  ICMJE
 (submitted: September 1, 2017)
  • Rate of rescue ECT in the HIKER arm [ Time Frame: From date of randomization up to 6 days ]
    Percent of patients in the HIKER arm who do not achieve a 25% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) after the third treatment.
  • Suicidal ideation [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Suicidal ideation as measured by the Columbia Suicide Severity Rating Scale
  • Cognitive Impairment [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Cognitive Impairment as measured by Mini-Mental State Exam
  • Self- and clinician rated improvement [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Patients will rate their condition on the patient-rated clinical global impression - improvement scale (PGI-I)
  • Patient satisfaction with treatment [ Time Frame: From date of randomization until the date of disease remission or after 8 treatments and at 30 days following last treatment, assessed up to 8 weeks ]
    Satisfaction with treatment will be assessed by the 2-item treatment satisfaction questionnaire for medication-version II (TSQM-GS-II).
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE ECT With Ketamine Anesthesia vs High Intensity Ketamine With ECT Rescue for Treatment-Resistant Depression
Official Title  ICMJE A Prospective Randomized Controlled Trial of Electroconvulsive Therapy With Ketamine Anesthesia (Standard Therapy) and High Intensity Ketamine With Electroconvulsive Therapy Rescue for Treatment-Resistant Depression - EAST HIKER Trial
Brief Summary To determine if an high intensity ketamine with ECT rescue (HIKER) approach for treatment resistant depression will: 1) reduce patient suffering by hastening disease remission, 2) have fewer side effects, 3) reduce the need for ECT, and 4) be preferred by most patients. Half of participants will be randomized to the HIKER arm and receive high intensity ketamine treatment for eight consecutive days, and the other half will be assigned to the ECT with ketamine anesthesia (EAST) arm and receive 8 ECT treatments (2-3 treatment/week)
Detailed Description

Major depressive disorder (MDD) is a common psychiatric illness that will affect at least 15% of the population. The burden of MDD is staggering, considered by the World Health Organization to be the leading cause of disability in developed countries for people aged 15-44.

Oral antidepressant therapy for MDD is notoriously ineffective. At least 3 weeks of treatment is usually required to achieve response rates that rarely exceed 40% (only 10% better than placebo); furthermore, treatment can be complicated by serious side effects serious (e.g. falls, weight gain) including increased suicidality. Up to 15% of patients will eventually be diagnosed as having treatment-resistant depressions (TRD), defined as the failure to respond to at least two antidepressants from different pharmacologic classes after adequate treatment duration at therapeutic dosages. The gold standard therapy for TRD is electroconvulsive therapy (ECT) with general anaesthesia (GA), which produces rapid antidepressant effects after only a few sessions. Propofol is the traditional anaesthetic agent used in GA for ECT, although recently this research group showed that ECT with ketamine as the primary anaesthetic produced faster depression remission compared to ECT with propofol.

Despite its efficacy, ECT is associated with considerable problems. More than 10% of patients will experience amnesia and confusion, which can persist for weeks. These cognitive side effects limit the frequency of ECT treatments to two or three times per week. There is also a risk of rare but devastating cardiorespiratory adverse events, at least part of which can be attributed to the need to induce chemical paralysis (for safety) and administer opioids (for pain control) during ECT with GA. Lastly, ECT requires specialized psychiatric expertise, dedicated resources, specially trained nurses, and an anaesthesiologist - requirements that are both costly and not readily available in many settings.

In contrast to ECT, daily short-acting anaesthesia, including ketamine, is well tolerated. A recent study found that only three treatments of intravenous ketamine produced a greater early improvement in depression scores compared to ECT under non-ketamine-based GA. This suggests a possibility of achieving early disease remission in TRD with ketamine-only infusions while avoiding the safety risks and treatment delays associated with ECT under GA.

The efficacy, feasibility, and improved side-effect profile of frequent successive ketamine treatments suggest it may be the preferred treatment for TRD compared to ECT with ketamine-based GA. There may, however, be a small subgroup of TRD patients who do not respond to ketamine alone and require ECT, although with a daily treatment regimen, ketamine non-responders could be quickly identified and given a standard course of ECT. The researchers propose that a treatment protocol of daily High Intensity Ketamine with ECT Rescue (HIKER) will be superior to ECT Therapy with ketamine anesthesia standard therapy (EAST) in facilitating early disease remission, while at the same time yielding similar overall remission rates by allowing ketamine non-responders to be quickly identified and given ECT.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
Patients in the EAST arm will receive eight ECT sessions (on a bi/triweekly schedule, weekdays only) with ketamine-based general anesthetic (ketamine 0.75 mg/kg, remifentanil 1 mcg/kg, and succinylcholine 0.75 mg/kg for safety. Patients in the HIKER arm will receive a single dose of ketamine 0.50 mg/kg, on 8 successive weekdays. Since ketamine without ECT is not the standard of care for TRD, patients in the HIKER arm who do not achieve a 25% reduction in the Montgomery-Asberg Depression Rating Scale (MADRS) after the third treatment will be deemed non-responsive to ketamine and switched to a standard 8 treatment course of ECT with ketamine-based GA as described in the EAST arm - this will be called rescue ECT. The attending psychiatrist may discontinue therapy for either arm if the patient achieves remission or treatment is ineffective based on clinical judgment.
Masking: Single (Investigator)
Masking Description:
Patients will be randomized to either the HIKER or EAST arms, but due to the different frequencies of treatment, patient and physician blinding will not be possible. Outcome assessor will also not be blinded. As patients were not blinded, they could easily divulge their treatment allocation. The outcome assessor can also deduce treatment allocation from communications with nursing staff or study personnel. However, the follow up assessment at 30 days post-final treatment will be performed by a different study team member who will remain blinded.
Primary Purpose: Treatment
Condition  ICMJE
  • Treatment Resistant Depression
  • Ketamine
Intervention  ICMJE
  • Drug: Ketamine
    IV Ketamine 0.50 mg/kg
    Other Name: Ketalar
  • Procedure: ECT
    ECT with unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method
Study Arms  ICMJE
  • Experimental: Ketamine (HIKER)
    Patients in the HIKER arm will receive a single dose of ketamine 0.50 mg/kg, which is enough to achieve a full anaesthetic effect (i.e., unconsciousness mimicking the GA regimen above), on 8 successive weekdays.
    Intervention: Drug: Ketamine
  • Active Comparator: Ketamine-ECT (EAST)
    Patients in the EAST arm will initially receive intravenous ketamine 0.75 mg/kg, remifentanil 1 mcg/kg (to reduce discomfort), and succinylcholine 0.75 mg/kg (for safety). Based on patients' anaesthetic response, the attending anaesthesiologist is given the freedom to vary the dose of remifentanil and succinylcholine as well as administer propofol to achieve safe and acceptable anaesthetic conditions. As per the Saskatoon Health Region's care standard, patients in the EAST arm will receive eight ECT sessions (on a bi/triweekly schedule) delivered by the attending psychiatrist with either unilateral or bilateral electrode placement and monitoring of seizure threshold by the half-age method.
    Interventions:
    • Drug: Ketamine
    • Procedure: ECT
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: September 1, 2017)
62
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 30, 2019
Estimated Primary Completion Date June 30, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Montgomery Asberg Depression Rating Scale (MADRS) score of greater than 20) planned for ECT therapy.
  • Subjects must meet clinical criteria for TRD defined as failure to respond to at least 2 standard-of-care drug therapies of adequate treatment duration.

Exclusion Criteria:

  • Subjects will be ineligible if they cannot provide informed consent
  • American Society of Anesthesiology physical status score of four or greater
  • Implanted medical device with electronic parts (e.g. pacemaker, defibrillator, intrathecal pump, spinal cord stimulator, deep brain stimulator)
  • Schizoaffective disorder
  • Women of child-bearing potential will be asked to undergo a commercial urine pregnancy screening test. Those who refuse or screen positive will be excluded.
  • Allergic to any of the study drugs or their carrier components
  • Any serious physical condition prior to randomization deemed by the attending psychiatrist or consulting anesthetist to be a contraindication to ECT such as cardiovascular disease (including untreated hypertension), respiratory disease, cerebrovascular disease, intracranial hypertension (including glaucoma), or seizures.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Stephen Lee, MD 3065010928 easthikerstudy@gmail.com
Contact: Edmond Li, MD 3066551183 easthikerstudy@gmail.com
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03272698
Other Study ID Numbers  ICMJE 123456
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Jonathan Gamble, University of Saskatchewan
Study Sponsor  ICMJE University of Saskatchewan
Collaborators  ICMJE Royal University Hospital Foundation
Investigators  ICMJE
Principal Investigator: Jonathan Gamble, MD University of Saskatchewan
PRS Account University of Saskatchewan
Verification Date April 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP