Aripiprazole for Refractory major depression disorder (RMDD) | Major depressive disorder

Inclusion criteria

• {"criterion_text":"- Patients between 60-74 years\n- To be receiving antidepressant treatment that includes an an SSRI (Selective Serotonin Reuptake Inhibitors) /SNRI (Serotonin–norepinephrine reuptake inhibitors) at the time of screening that is not responding (less than 25% improvement in symptoms) after receiving an adequate dose [SmPC; or local equivalent, if applicable] for at least 6 weeks and have been increased to the dose maximum allowed\n- 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)\n- 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)\n- To be taking a single oral antidepressant on day 1 before randomization\n- 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."}

Exclusion criteria

• {"criterion_text":"- Treatment with drugs contraindicated with the use of esketamine and aripiprazole.\n- 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\n- Patients who are participating in another clinical trial with active treatment\n- 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\n- Hypersensitivity to any of the active ingredients of any of the branches of treatment, or to any of the excipients of its pharmaceutical form\n- Patients in whom increased blood pressure or blood pressure intracranial fluid poses a serious risk"}

Primary endpoints

• {"endpoint_text":"- Clinical response at week 8 after initiation of treatment, 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 with respect to the initial score and a score ≤4 on the CGI severity scale.","definition_or_measurement_approach":"Measured using MADRS: remission defined as total MADRS score ≤10; adequate clinical response defined as ≥50% reduction in total MADRS score from baseline and a score ≤4 on the CGI-Severity scale."}

Secondary endpoints

• {"endpoint_text":"- Clinical response at week 32 after initiation of treatment, 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 with respect to the initial score and a score ≤4 on the CGI severity scale.","definition_or_measurement_approach":"Measured using MADRS and CGI-S criteria as for primary endpoint at week 32."}
• {"endpoint_text":"- Determination of the safety profile of esketamine nasal spray and aripiprazole at week 8, as assessed by the established safety committee","definition_or_measurement_approach":"Safety assessed and determined by the established safety committee (details in protocol/SMPCs)."}
• {"endpoint_text":"- Determination of the safety profile of esketamine nasal spray and aripiprazole at week 32 in those patients who were relapse-free at week 8, as assessed by the established safety committee","definition_or_measurement_approach":"Safety assessed by the established safety committee in the subgroup relapse-free at week 8."}
• {"endpoint_text":"- Proportion of patients free of relapse at week 24 and week 32 in the group of patients with clinical remission at week 8.","definition_or_measurement_approach":"Proportion (percentage) of patients meeting relapse-free status at weeks 24 and 32 among those with clinical remission at week 8."}
• {"endpoint_text":"- Score on the EuroQol-5D (EQ-5D) scale for health-related quality of life in adults","definition_or_measurement_approach":"Measured using the EQ-5D instrument; endpoint is EQ-5D score."}
• {"endpoint_text":"- Whole genome sequencing of trial participants using variant filtering and prioritization routinely performed in the HUVR laboratory.","definition_or_measurement_approach":"Whole genome sequencing with variant filtering/prioritization as routinely performed in the HUVR laboratory."}
• {"endpoint_text":"- Obtaining the transcriptome of trial participants at week 8 and week 32 of treatment using a large-scale sequencer","definition_or_measurement_approach":"Transcriptome (RNA-seq) obtained at baseline? (protocol specifies week 8 and week 32) using large-scale sequencer."}
• {"endpoint_text":"- Integration of participants’ exome and transcriptome findings with other omics.","definition_or_measurement_approach":"Integration of exome and transcriptome data with other omics datasets per protocol methods."}
• {"endpoint_text":"- To determine the immune activation and inflammation profiles in both treatment groups","definition_or_measurement_approach":"Determined using multiple plasma markers to profile immune activation and inflammation."}
• {"endpoint_text":"- Deep immunophenotyping by flow cytometry of peripheral blood cells in both treatment groups","definition_or_measurement_approach":"Deep immunophenotyping performed by flow cytometry on peripheral blood cells."}
• {"endpoint_text":"- Determine the activity profiles of relevant pathways in both treatment arms","definition_or_measurement_approach":"Activity profiles of relevant pathways determined (methodology per protocol/omics analyses)."}

Spain

Earliest CTIS Part Ii Submission Date

23-08-2024

Latest Decision Or Authorization Date

23-10-2025

Processing Time Days

426

Number Of Sites

11

Number Of Participants

220

Primary sponsor

Full Name

Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

Spain

Third parties

• {"country":"","full_name":"ISCIII institute public funding EXP ICI23_00029","duties_or_roles":"Monetary support / funding","organisation_type":""}