Major Depressive DisorderPhase 4NCT03861988
Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
A Phase 4 study testing Ketamine in people with Major Depressive Disorder and Surgery, run by Stanford University at 1 site in United States.
Trial summary
This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Major Depressive Disorder, Surgery, Orthopedic Disorder
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- 22 Aug 2019to 27 Sep 2022
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient presenting for non-cardiac, non-intracranial surgery
- Major Depressive Disorder
Who cannot join
- Pregnant of breastfeeding women
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Double-blind Trial of Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery.
Read the detailed description
Major Depressive Disorder (MDD) is widely prevalent among patients preparing to have surgery, and is a known risk factor for complications after surgery, including wound infection, myocardial infarction and opioid use disorder. Ketamine has emerged as an effective, rapid-acting antidepressant therapy for patients with MDD, and may be a useful tool to prevent MDD-related morbidity in the perioperative period. Ketamine has been well studied for MDD in outpatient clinics where it is given as an infusion (0.5 mg/kg over 40 minutes) in awake patients. Ketamine is often used as part of an anesthetic cocktail in sedated or anesthetized patients, but it is unknown whether ketamine has an antidepressant effect in this context. The investigators will determine whether a ketamine infusion, compared to placebo (normal saline infusion), has an antidepressant effect when given during surgical anesthesia. If ketamine is an effective antidepressant in this population under anesthesia, its use could be incorporated into a set of interventions to minimize the perioperative complications associated with MDD.
- Conditions
- Major Depressive Disorder, Surgery, Orthopedic Disorder
- Being tested
- Ketamine, Normal saline (placebo)
- Keywords
- depression, ketamine, anesthesia, total joint arthroplasty
- Medical subject headings
- Depressive Disorder, Major, Musculoskeletal Diseases, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar.
0.5 mg/kg over 40 minutes, intravenous.
Normal saline (placebo)Drug
Normal saline infusion over 40 minutes, equivalent volume to ketamine infusion.
| Study group | Role | What they receive |
|---|---|---|
| Open label ketamine | Experimental | Patients will receive an intravenous ketamine infusion during surgery. Receives: Drug: Ketamine |
| Double blind ketamine | Experimental | Patients will receive an intravenous ketamine infusion during surgery. Receives: Drug: Ketamine |
| Double blind placebo | Placebo comparator | Participants will receive placebo (normal saline infusion) during surgery. Receives: Drug: Normal saline (placebo) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Montgomery-Asberg Depression Rating Scale (MADRS) Score
The MADRS is a 10-item scale for the evaluation of depressive symptoms (Montgomery et al 1979). Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where lower MADRS scores indicate lower levels of depressive symptoms. The assessment for this outcome will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) was used to analyze the difference in postoperative MADRS score between ketamine and placebo groups..
Measured: Post-intervention days 1, 2 and 3
Secondary outcomes (7)
Number of Participants With Clinical Response
Clinical response defined as >=50% reduction in MADRS score from baseline. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms.
Measured: Post-intervention days 1, 2 and 3
Number of Participants With Remission
Remission defined as a MADRS score of <=12 on day 14. MADRS score range: 0 to 60, a lower score indicates lower severity of symptoms.
Measured: Post-intervention day 14
Hospital Anxiety and Depression Scale (HADS) Scale Score
This outcome measures self-reported symptoms of anxiety and depression on a scale that ranges from 0 to 42. A lower score indicates lower severity of symptoms.
Measured: Post-intervention days 1, 2, 3, 5, 7 and 14
Cumulative Opioid Use
This outcome measures how many cumulative morphine-equivalents milligrams of opioid pain medication the patient has taken as an inpatient and after discharge from hospital
Measured: Post-intervention days 1, 2, 3, 5, 7 and 14
Hospital Length of Stay
Number of days from admission (day of surgery) through discharge after surgery.
Measured: Average approximately 3 days post-intervention
Brief Pain Inventory Pain Intensity Scale Score
Average pain intensity in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing "No pain" and 10 representing "Pain as bad as you can imagine").
Measured: Post-intervention days 1, 2, 3, 5, 7 and 14
Brief Pain Inventory Pain Interference Scale Score
Pain interference in the past 24 hours, rated on a numerical scale from 0 to 10 (with 0 representing "Does not interfere" and 10 representing "Completely interferes").
Measured: Post-intervention days 1, 2, 3, 5, 7 and 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Mar 2019
- Study start22 Aug 2019
- Primary completion22 Sep 2022
- Study completion27 Sep 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Boris D. Heifets, Stanford University
- Investigators
- Boris D Heifets, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03861988
- Sponsor's protocol ID
- 49114
- Status last verified
- Oct 2023
- First submitted
- 1 Mar 2019
- Last updated
- 5 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No: No current plan to share data.
Publications
Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.
PubMed 444788Lii TR, Smith AE, Flohr JR, Okada RL, Nyongesa CA, Cianfichi LJ, Hack LM, Schatzberg AF, Heifets BD. Randomized trial of ketamine masked by surgical anesthesia in patients with depression. Nat Ment Health. 2023 Nov;1(11):876-886. doi: 10.1038/s44220-023-00140-x. Epub 2023 Oct 19.
PubMed 38188539Lii TR, Smith AE, Flohr JR, Okada RL, Nyongesa CA, Cianfichi LJ, Hack LM, Schatzberg AF, Heifets BD. Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients. medRxiv [Preprint]. 2023 Jun 15:2023.04.28.23289210. doi: 10.1101/2023.04.28.23289210.
PubMed 37205558
Study at a glance
From the registry record, last updated by the sponsor on 5 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-blind Trial of Intraoperative Ketamine Versus Saline in Depressed Patients Undergoing Anesthesia for Non-cardiac Surgery
- ClinicalTrials.gov ID
- NCT03861988
- Acronym / sponsor ID
- 49114
- Conditions
- Major Depressive Disorder, Surgery, Orthopedic Disorder
- Keywords
- depression, ketamine, anesthesia, total joint arthroplasty
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Study start
- 22 Aug 2019 (actual)
- Primary completion
- 22 Sep 2022 (actual)
- Study completion
- 27 Sep 2022 (actual)
- First posted
- 5 Mar 2019 (actual)
- Results
- Posted 5 Oct 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study evaluates whether ketamine, given as part of an anesthetic, improves depression symptoms in depressed patients undergoing non-cardiac surgery. Half of participants will receive a ketamine infusion during surgery, while the other half will receive a placebo (normal saline) during surgery.
Detailed description
Major Depressive Disorder (MDD) is widely prevalent among patients preparing to have surgery, and is a known risk factor for complications after surgery, including wound infection, myocardial infarction and opioid use disorder. Ketamine has emerged as an effective, rapid-acting antidepressant therapy for patients with MDD, and may be a useful tool to prevent MDD-related morbidity in the perioperative period. Ketamine has been well studied for MDD in outpatient clinics where it is given as an infusion (0.5 mg/kg over 40 minutes) in awake patients. Ketamine is often used as part of an anesthetic cocktail in sedated or anesthetized patients, but it is unknown whether ketamine has an antidepressant effect in this context. The investigators will determine whether a ketamine infusion, compared to placebo (normal saline infusion), has an antidepressant effect when given during surgical anesthesia. If ketamine is an effective antidepressant in this population under anesthesia, its use could be incorporated into a set of interventions to minimize the perioperative complications associated with MDD.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Open label ketamine | Experimental | Drug: KetaminePatients will receive an intravenous ketamine infusion during surgery. |
| Double blind ketamine | Experimental | Drug: KetaminePatients will receive an intravenous ketamine infusion during surgery. |
| Double blind placebo | Placebo comparator | Drug: Normal saline (placebo)Participants will receive placebo (normal saline infusion) during surgery. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient presenting for non-cardiac, non-intracranial surgery
- Major Depressive Disorder
Key exclusion criteria (1 listed)
- Pregnant of breastfeeding women
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| KetamineAlso: Ketalar.0.5 mg/kg over 40 minutes, intravenous. | Drug | Double blind ketamine, Open label ketamine |
| Normal saline (placebo)Normal saline infusion over 40 minutes, equivalent volume to ketamine infusion. | Drug | Double blind placebo |
Primary outcome
Montgomery-Asberg Depression Rating Scale (MADRS) Score
Time frame: Post-intervention days 1, 2 and 3
The MADRS is a 10-item scale for the evaluation of depressive symptoms (Montgomery et al 1979). Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where lower MADRS scores indicate lower levels of depressive symptoms. The assessment for this outcome will be taken once daily on days 1, 2 and 3 post procedure. A mixed model for repeated measures (MMRM) was used to analyze the difference in postoperative MADRS score between ketamine and placebo groups..
7 secondary outcomes
Number of Participants With Clinical Response
Time frame: Post-intervention days 1, 2 and 3
Number of Participants With Remission
Time frame: Post-intervention day 14
Hospital Anxiety and Depression Scale (HADS) Scale Score
Time frame: Post-intervention days 1, 2, 3, 5, 7 and 14
Cumulative Opioid Use
Time frame: Post-intervention days 1, 2, 3, 5, 7 and 14
Hospital Length of Stay
Time frame: Average approximately 3 days post-intervention
Brief Pain Inventory Pain Intensity Scale Score
Time frame: Post-intervention days 1, 2, 3, 5, 7 and 14
Brief Pain Inventory Pain Interference Scale Score
Time frame: Post-intervention days 1, 2, 3, 5, 7 and 14
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 444788Montgomery SA, Asberg M. A new depression scale designed to be sensitive to change. Br J Psychiatry. 1979 Apr;134:382-9. doi: 10.1192/bjp.134.4.382.
- Derived from this study: PubMed 38188539Lii TR, Smith AE, Flohr JR, Okada RL, Nyongesa CA, Cianfichi LJ, Hack LM, Schatzberg AF, Heifets BD. Randomized trial of ketamine masked by surgical anesthesia in patients with depression. Nat Ment Health. 2023 Nov;1(11):876-886. doi: 10.1038/s44220-023-00140-x. Epub 2023 Oct 19.
- Derived from this study: PubMed 37205558Lii TR, Smith AE, Flohr JR, Okada RL, Nyongesa CA, Cianfichi LJ, Hack LM, Schatzberg AF, Heifets BD. Randomized Trial of Ketamine Masked by Surgical Anesthesia in Depressed Patients. medRxiv [Preprint]. 2023 Jun 15:2023.04.28.23289210. doi: 10.1101/2023.04.28.23289210.
- Individual participant dataSharing planned: No. No current plan to share data.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Boris D Heifets, MD, PhD principal investigator
Stanford University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine in people with Major Depressive Disorder and Surgery, run by Stanford University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 5 Oct 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Montgomery-Asberg Depression Rating Scale (MADRS) Score (time frame: Post-intervention days 1, 2 and 3). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03861988, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Oct 2023.