A real world assessment for Safety and effectiveness of VORtioxeTine and Escitalopram with Clonazepam in anXious depression

A real world assessment for safety and effectiveness of VORtioxeTine and Escitalopram with Clonazepam in anXious depression (VORTEX STUDY)

STUDY CODE – IIS2312013

CLINICAL STATE:

Patients with Major Depressive Disorder (MDD) with Anxiety or Anxious depression.

OBJECTIVES:

To assess the effectiveness & safety of Vortioxetine and Escitalopram with Clonazepam in patients of MDD with anxiety.

STUDY POPULATION:

200 cases from 5 centres across India

STUDY DESIGN:

Post approval, prospective, multicentre, longitudinal, open-label study

STUDY ENDPOINTS:

PRIMARY ENDPOINT:

 Change in Montgomery-Åsberg Depression Rating Scale (MADRS) total score from baseline to 2 and 6 week.

 Change in Hamilton Anxiety Rating Scale for Anxiety (HAM –A) total scores from baseline to 2 and 6 week.

SECONDARY ENDPOINTS:

 Clinical Global Impression for Efficacy Index (CGI-EI) at 2 and 6 Week

 Treatment Emergent Adverse event (TEAE) assessment at every scheduled visit

 Change in Sexual function or ASEX score from baseline to 2 week and 6 week

NUMBER OF PATIENTS (PLANNED/SITE):

Each site will assess 40 cases of anxious depression (20 patients on Vortioxetine & 20 patients on Escitalopram) along with clonazepam. Such five sites will be enrolled across India.

MAIN CRITERIA FOR INCLUSION:

 Male or female patients 18 to 65 years with DSM-V defined MDD with anxious depression.

 Treatment naïve patients or known cases already on VOR or ESC not exceeding two weeks of active treatment.

 Patients with MADRS score ≥ 20 and HAM-A score ≥ 25.

 Patient with normal physical examination, clinical laboratory, and ECG findings (as per physician’s discretion)

 Patients who are willing to sign the informed consent form.

MAIN EXCLUSION CRITERIA:

 Patient aged less than 18 years and more than 65 years will be excluded.

 Patient with MADRS < 19 and HAM-A < 24.

 Patients requiring second generation antipsychotics or lithium.

 Patient in which the use of benzodiazepine is contraindicated.

 Patient with other conditions who do not fit into the criteria of the study as per the protocol.

 Patient with known hypersensitivity to Vortioxetine, Escitalopram, Clonazepam or any excipients.

 Patients who are not willing to sign the informed consent form.

DURATION OF STUDY: 4 months

DURATION OF OBSERVATION: 6 weeks

STUDY METHODOLOGY:

ï‚· Post approval, prospective, multi-centre, open label study to be conducted at 5 sites across India to assess the effectiveness & safety of Vortioxetine and Escitalopram with Clonazepam in patients of MDD with anxiety.

ï‚· In total, 200 Patients from 5 different centres in India will be enrolled.

ï‚· Each site will enrol 20 cases of MDD in each arm of Vortioxetine and Escitalopram for patients requiring co-prescription of BDZ as clonazepam.

ï‚· This is a real world assessment of SSRIs in MDD as an observational study with the cases prospectively recruited with their informed consent for participation with scientific utilization of findings as publication.

 At screening, demographic data (age, sex, weight, height, family history, and significant medical history and comorbidity), MADRS, HAM-A, ASEX, and Anhedonia subscale score will be recorded. If the subject qualifies the inclusion criteria i.e. MADRS ≥ 20 “AND” HAM ≥ 25, he/she will be enrolled to either Vortioxetine OR Escitalopram along with Clonazepam.

 Vortioxetine or Escitalopram will be initiated at @10mg OD for 6 weeks with fortnightly assessment of dose for therapeutic efficacy as ≥50% drop in MADRS and HAM-A score along with Clonazepam 0.5 or 1mg OD.

ï‚· In case of suboptimal response at 2nd week, the therapeutic dose will be modified at the discretion of the physician/ specialist taking into consideration the risk benefit ratio before treatment withdrawal in case of any SAE or AE of severe intensity.

ï‚· Follow up visit at 2nd week will assess MADRS, HAM-A, ASEX, Anhedonia subscale.

ï‚· Follow up visit at 6th week will assess in addition the CGI-EI taking into consideration the symptomatic therapy involving PPIs that may be co-prescribed to foster patient compliance and adherence to therapy.

ï‚· No other antidepressants including Melatonin, Aglomelatine, SNRIs, TCAs or SGAs will be considered for Full Set Analysis on the primary end points

ï‚· In case of AE and SAE, the intensity, prognostication and cause effect relationship will be captured on CRF and CDSCO suspect ADR sheet.

ï‚· In case of SAE, the clinical investigator needs to report the Event information on CDSCO Suspect ADR Report Form once aware of the event as Date of Awareness (DOA) in addition to Date of Event (DOE).

CRITERIA FOR EVALUATION:

ï‚· Change in MADRS, HAM-A, ASEX, Anhedonia and CGI-EI scale indices at 2nd and 6th week.

 Safety: Adverse events: as per WHO classification, incidence of ‘Common’ Treatment emergent adverse events of ≥ 1%.

STATISTICAL METHODS:

ï‚· Demographic data will be presented using descriptive statistics in the form of the frequencies and percentages

 Change in continuous and categorical variables will be assessed for significance using the ANOVA and Fischer’s exact test respectively with P<0.05 considered to be clinically significant using the two tailed test

ï‚· This is the post approval, longitudinal, non-inferiority, and parallel multi centric clinical study to assess the clinical impact of Vortioxetine and Escitalopram along with Clonazepam in MDD cases. Taking into the consideration treatment related intergroup difference in MADRS as -0.5 +/- 0.5 with non-inferiority margin of 20%, a total of 200 cases will be enrolled while taking into consideration 30% case drop-out rate during the course of observation period.