Depressive DisorderPhase 3CESARNCT07153406
Comparison of Esketamine Nasal Spray vs.Aripiprazole in Treat.Resistant Major Depressive Disorder in Elderly Patients
A Phase 3 study testing Experimental regimen in people with Depressive Disorder, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 9 sites in Spain.
Trial summary
Phase III, open label, randomised, multicentre, blind for evaluators clinical trial to evaluate the efficacy of esketamine nasal spray at flexible dosis compared to aripiprazole in elderly participants (>60 years) who suffer from treatment-resistant major depressive Read more about this study
- Who is it for?
- Ages 60 to 74 years
- Conditions the study is for
- Depressive Disorder
- What is being tested?
- Experimental regimen
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 220 participants
- Where
- 9 sitesSpain
- Study dates
- 15 Sep 2025to 15 Jan 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
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 60 to 74 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients between 60-74 years
- To be receiving antidepressant treatment that includes an antidepressant at the time of screening that is not responding (less than 25% improvement in symptoms) after receiving an adequate dose [or local equivalent, if applicable] for at least 6 weeks and have been increased to the dose maximum allowed
- Current antidepressant treatment must have been immediately preceded by failure to respond to at least 3, but not more than 5, different consecutive treatments (all within the same moderately severe depressive episode) with antidepressant drugs (AD) taken at an appropriate dose for at least least 6 weeks (3 antidepressant failures including the current one)
- To have been treated with at least 3 different classes of antidepressants between treatments taken at appropriate doses for at least 6 weeks without response in the current moderate to severe depressive episode (including current treatment with an antidepressant)
- To be taking a single oral antidepressant on day 1 before randomization
- Participants who, at the time of screening, are taking a combination of antidepressants and/or rescue treatment (other than aripiprazole) for the current moderate to severe depressive episode may participate in the study.
Who cannot join
- Treatment with drugs contraindicated with the use of esketamine and aripiprazole.
- Patients in whom a high risk of suicide is detected at the screening visit, according to the criteria established by Columbia University according to the C-SSRS evaluation
- Patients who are participating in another clinical trial with active treatment
- Patients who do not have the capacity to consent to participation in the trial or who do not have a representative to confirm their participation
- Hypersensitivity to any of the active ingredients of any of the branches of treatment, or to any of the excipients of its pharmaceutical form
- Patients in whom increased blood pressure or blood pressure intracranial fluid poses a serious risk
Trial locations and contacts
9 sites in 1 country. Contact the study team or a site near you to ask about taking part.
9 sites in 1 country
Spain9 sites
Hospital Vall d'Hebron
Barcelona, 08014
Hospital De La Santa Creu i Sant Pau
Barcelona, 08041
Narcís Cardoner Álvarez, MD, +34932183217, ncardoner@santpau.cat
Hospital Mare de Déu de La Mercè
Barcelona, 08042
Silvana Carolina Roca Bassani, MD, +34934275250, scroca.merced@hospitalarias.es
Hospital Sagrat Cor. Martorell
Barcelona, 08760
Manuel Sánchez Pérez, MD, +34937752200, hospital.hsagratcor@hospitalarias.es
Hospital Benito Menni y Fidmag Hermanas Hospitalarias
Barcelona, 08830
Joan Soler Vidal, MD, +34650113820, jsoler@fidmag.org
Centro Sociosanitario Hermanas Hospitalarias de Palencia
Palencia, 34004
Carlos Martín Lorenzo, +34979165324, carlosmartin@fidmag.org
Clínica Psiquiátrica Padre Menni
Pamplona, Navarre, 31014
José Joaquín Roldán Larreta, MD, +34948140611, jjroldan.mennipamplona@hospitalarias.es
Corporacion Sanitaria Parc Tauli
Sabadell, 08208
Virginia Soria Tomás, MD, +34937231010, vsoria@tauli.cat
Hospital Universitario Virgen del Rocio
Seville, 41013
Benedicto Crespo Facorro, MD, +34955013491, bcrespo@us.es
About this study
Official title: Comparison of Esketamine Versus Aripiprazole,Both in Combination With a SSRI/SNRI(Selective Serotonin Reuptake Inhibitors/Serotonin and Norepinephrine Reuptake Inhibitors )in Treatment-resistant Major Depressive Disorder in Elderly Patients
Phase III, open label, randomised, multicentre, blind for evaluators clinical trial to evaluate the efficacy of esketamine nasal spray at flexible dosis compared to aripiprazole in elderly participants (>60 years) who suffer from treatment-resistant major depressive
Read the detailed description
The study disease is resistant major depressive disorder, which has not responded to at least three different strategies with antidepressants, at least one of them being a combination or potentiation strategy, with a current moderate-severe depressive episode.
The aim of the study is to evaluate the efficacy of esketamine nasal spray at flexible dosis compared to aripiprazole at 8 weeks, both in combination with a continued antidepressant, in elderly participants (>60 years), who suffer from treatment-resistant major depressive disorder with one episode current moderate to severe depressive disorder
- Conditions
- Depressive Disorder
- Being tested
- Experimental regimen, Control regimen
- Keywords
- Depressive Disorder, Moderate-severe depressive episode., Antidepressants, Psychotropics
- Medical subject headings
- Depressive Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Experimental regimenDrug
Esketamine intranasal spray at flexible doses (28, 56 and 84 mg) once or twice a week
Control regimenDrug
Oral aripiprazole 5-30 mg daily, once or twice daily for the duration of the study
| Study group | Role | What they receive |
|---|---|---|
| Esketamine | Experimental | Esketamine intranasal spray at flexible doses 28, 56 and 84 mg once or twice a week Receives: Drug: Experimental regimen |
| aripiprazole | Active comparator | Oral aripiprazole 5-30 mg daily, once or twice daily for the duration of the study Receives: Drug: Control regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical response
Clinical response at week 8 after initiation of treatment, measured in terms of:
- Remission of depressive symptoms; total score ≤10 on the MADRS (Montgomery-Asberg Depression Rating Scale )scale.
- Adequate clinical response, if they show a reduction of ≥50% in the total score of the MADRS scale with respect to the initial score and a score ≤4 on the CGI severity scale. (Clinical Global Impression)
Measured: At week 8
Secondary outcomes (6)
Safety profile of esketamine nasal spray and aripiprazole
Determination of the safety profile of esketamine nasal spray and aripiprazole in patients free of relapse at week 32, according to the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 throughout the study.
Measured: At week 32
Clinical response
Clinical response measured in terms of:
- Remission of depressive symptoms; total score ≤10 on the MADRS scale.
- Adequate clinical response, if they show a reduction of ≥50% in the total score of the MADRS scale compared to the initial score and a score ≤4 on the CGI severity scale.
Measured: At week 32
Safety profile of esketamine nasal spray and aripiprazole
Determination of the safety profile of esketamine nasal spray and aripiprazole at week 8, according to the number of participants with treatment-related adverse events as assessed by CTCAE v4.0 throughout the study.
Measured: At week 8
Free of relapse
Proportion of patients free of relapse at week 24 and week 32 in the group of patients with clinical remission at week 8.
Measured: At week 24, at week 32
Score on the EuroQol-5D scale (www.euroqol.org)
Score on the EuroQol-5D (EQ-5D) health-related quality of life scale in adults
Measured: At day 1, at day 8, at day 15, at day 22, at week 5 to 8, at week 9 to 32, at week 34
Obtaining the transcriptome
Obtaining the transcriptome of patients at week 8 and week 32 of treatment using a large-scale sequencer.
Measured: At week 8, at week 32
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2025
- Study start15 Sep 2025 (estimated)
- Primary completion15 Sep 2026 (estimated)
- Study completion15 Jan 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Depressive DisorderStudies of the same condition, open and under way.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 220 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Benedicto Crespo Facorro, MD, Principal investigator, Fundación para la Gestión de la Investigación en Salud de Sevilla
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07153406
- Sponsor's protocol ID
- CESAR
- Acronym
- CESAR
- Status last verified
- Aug 2025
- First submitted
- 25 Oct 2024
- Last updated
- 4 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Esketamine Versus Aripiprazole,Both in Combination With a SSRI/SNRI(Selective Serotonin Reuptake Inhibitors/Serotonin and Norepinephrine Reuptake Inhibitors )in Treatment-resistant Major Depressive Disorder in Elderly Patients
- ClinicalTrials.gov ID
- NCT07153406
- Acronym / sponsor ID
- CESAR / CESAR
- Conditions
- Depressive Disorder
- Keywords
- Depressive Disorder, Moderate-severe depressive episode., Antidepressants, Psychotropics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 220 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Study start
- 15 Sep 2025 (estimated)
- Primary completion
- 15 Sep 2026 (estimated)
- Study completion
- 15 Jan 2029 (estimated)
- First posted
- 4 Sep 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Phase III, open label, randomised, multicentre, blind for evaluators clinical trial to evaluate the efficacy of esketamine nasal spray at flexible dosis compared to aripiprazole in elderly participants (>60 years) who suffer from treatment-resistant major depressive
Detailed description
The study disease is resistant major depressive disorder, which has not responded to at least three different strategies with antidepressants, at least one of them being a combination or potentiation strategy, with a current moderate-severe depressive episode.
The aim of the study is to evaluate the efficacy of esketamine nasal spray at flexible dosis compared to aripiprazole at 8 weeks, both in combination with a continued antidepressant, in elderly participants (>60 years), who suffer from treatment-resistant major depressive disorder with one episode current moderate to severe depressive disorder
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Esketamine | Experimental | Drug: Experimental regimenEsketamine intranasal spray at flexible doses 28, 56 and 84 mg once or twice a week |
| aripiprazole | Active comparator | Drug: Control regimenOral aripiprazole 5-30 mg daily, once or twice daily for the duration of the study |
Who may qualify
- Ages
- 60 to 74 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients between 60-74 years
- To be receiving antidepressant treatment that includes an antidepressant at the time of screening that is not responding (less than 25% improvement in symptoms) after receiving an adequate dose [or local equivalent, if applicable] for at least 6 weeks and have been increased to the dose maximum allowed
- Current antidepressant treatment must have been immediately preceded by failure to respond to at least 3, but not more than 5, different consecutive treatments (all within the same moderately severe depressive episode) with antidepressant drugs (AD) taken at an appropriate dose for at least least 6 weeks (3 antidepressant failures including the current one)
- To have been treated with at least 3 different classes of antidepressants between treatments taken at appropriate doses for at least 6 weeks without response in the current moderate to severe depressive episode (including current treatment with an antidepressant)
- To be taking a single oral antidepressant on day 1 before randomization
Key exclusion criteria (6 listed)
- Treatment with drugs contraindicated with the use of esketamine and aripiprazole.
- Patients in whom a high risk of suicide is detected at the screening visit, according to the criteria established by Columbia University according to the C-SSRS evaluation
- Patients who are participating in another clinical trial with active treatment
- Patients who do not have the capacity to consent to participation in the trial or who do not have a representative to confirm their participation
- Hypersensitivity to any of the active ingredients of any of the branches of treatment, or to any of the excipients of its pharmaceutical form
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 |
|---|---|---|
| Experimental regimenEsketamine intranasal spray at flexible doses (28, 56 and 84 mg) once or twice a week | Drug | Esketamine |
| Control regimenOral aripiprazole 5-30 mg daily, once or twice daily for the duration of the study | Drug | aripiprazole |
Primary outcome
Clinical response
Time frame: At week 8
Clinical response at week 8 after initiation of treatment, measured in terms of: * Remission of depressive symptoms; total score ≤10 on the MADRS (Montgomery-Asberg Depression Rating Scale )scale. * Adequate clinical response, if they show a reduction of ≥50% in the total score of the MADRS scale with respect to the initial score and a score ≤4 on the CGI severity scale. (Clinical Global Impression)
6 secondary outcomes
Safety profile of esketamine nasal spray and aripiprazole
Time frame: At week 32
Clinical response
Time frame: At week 32
Safety profile of esketamine nasal spray and aripiprazole
Time frame: At week 8
Free of relapse
Time frame: At week 24, at week 32
Score on the EuroQol-5D scale (www.euroqol.org)
Time frame: At day 1, at day 8, at day 15, at day 22, at week 5 to 8, at week 9 to 32, at week 34
Obtaining the transcriptome
Time frame: At week 8, at week 32
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Sep 2025.
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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.
Benedicto Crespo Facorro, MD principal investigator
Fundación para la Gestión de la Investigación en Salud de Sevilla
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Experimental regimen in people with Depressive Disorder, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 9 sites in Spain.
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 6 inclusion and 6 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: opening soon, as of the sponsor's last update on 4 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain. 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. 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Clara M Rosso Fernández, MD-PhD (+34955013414, claram.rosso.sspa@juntadeandalucia.es), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical response (time frame: At week 8). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 4 Sep 2025.