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Trazodone Once a Day in Major Depression Disorder

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ClinicalTrials.gov Identifier: NCT02086929
Recruitment Status : Completed
First Posted : March 13, 2014
Last Update Posted : December 30, 2015
Sponsor:
Information provided by (Responsible Party):
Aziende Chimiche Riunite Angelini Francesco S.p.A

Brief Summary:
The study objective is to evaluate the efficacy and safety of trazodone OAD vs venlafaxine extended release (venlafaxine XR) after an 8-week treatment period in patients with major depressive disorder.

Condition or disease Intervention/treatment Phase
Major Depressive Disorder Drug: Trazodone Drug: Venlafaxine Phase 3

Detailed Description:
This randomized, venlafaxine-controlled, double-blind, parallel design study consists of a Pre-Treatment Phase (screening, wash-out) and a double-blind Treatment Phase (randomization to trazodone OAD or to venlafaxine XR, treatment for 8 weeks and tapering for 1 to 3 weeks). During the Pre-Treatment Phase, patients who sign an informed consent form will undergo initial screening. Potential candidates will be instructed to discontinue antidepressants or prohibited medications (wash-out) for a period specific to taper schedule (based on 5 elimination half-lives of the used medication). On the last day of the Pre-Treatment Phase, patients will be evaluated for the final eligibility, and those qualified will be randomly allocated in a 1:1 proportion to trazodone OAD 300 mg/day (1 week of tapering with trazodone OAD 150 mg/day) or to venlafaxine XR 75 mg/day once daily. After 3 and 5 weeks of treatment, subjects will be evaluated for the response. For non responding patients dose increases (in increments of 75 mg/day) will be done till to reach the maximum of 225 mg/day for venlafaxine XR and 450 mg/day for trazodone OAD. Patients non responding to treatment at the final visit will have their study medication tapered from 1 to 3 weeks, according to the maximum dose reached during the study. In order to prevent relapse of depression symptoms, responders at the final visit may continue the treatment. In this case, an unblinded third party Dispenser will open the treatment code and will prescribe the same medication taken by the patients during the trial, according to the formulation available on the market.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 364 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-blind Study Comparing the Efficacy and Safety of Trazodone OAD and Venlafaxine XR in the Treatment of Patients With Major Depressive Disorder.
Study Start Date : December 2012
Actual Primary Completion Date : April 2014
Actual Study Completion Date : April 2014

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Trazodone

300 mg/day for 8 weeks (including 1 week 150 mg/day of dose-titration). After 3 and 5 weeks of treatment, non responders will have dose increases (in increments of 75 mg/day) till to reach the maximum of 450 mg/day.

Dosage form: capsule.

Drug: Trazodone
Active Comparator: Venlafaxine XR

75 mg/die for 8 weeks. After 3 and 5 weeks of treatment, non responders will have dose increases (in increments of 75 mg/day) till to reach the maximum of 225 mg/day.

Dosage form: capsule.

Drug: Venlafaxine



Primary Outcome Measures :
  1. Hamilton Depression Rating Scale (HAMD) score [ Time Frame: Day 56 ]
    Mean change from baseline (Day 0) in HAMD score at Day 56.


Secondary Outcome Measures :
  1. Montgomery-Asberg Depression Rating Scale (MADRS) score [ Time Frame: Day 56 ]
    Mean change from baseline (Day 0) in MADRS score at Day 56.

  2. Clinical Global Impression (CGI) Severity of Illness score [ Time Frame: Day 56 ]
    CGI-Severity of Illness improvement at Day 56.

  3. Clinical Global Impression (CGI) Global improvement score [ Time Frame: Day 56 ]
    CGI-Global improvement at Day 56.

  4. Percentage of responders [ Time Frame: Day 56 ]
    Rate of patients with a 50% decrease with respect to baseline on the HAMD score at Day 56.

  5. Percentage of patients with remission [ Time Frame: Day 56 ]
    Rate of patients with a HAMD score <or= at Day 56.

  6. Safety profile of trazodone OAD compared to venlafaxine XR [ Time Frame: 11 weeks ]
    Safety and tolerability will be assessed through adverse events monitoring, physical examinations and monitoring of vital signs, body weight, clinical laboratory tests, ECG.



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Ages Eligible for Study:   18 Years to 75 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • men and women 18-75 years of age (limits included) with no limitation of race;
  • outpatients;
  • major depressive disorder according to DSM-IV criteria as assessed using the MINI International Neuropsychiatric Interview;
  • 17-item HAMD score > 18 at both screening and baseline visits with a decrease not exceeding 20% between screening and baseline;
  • symptoms of depression for at least one month before study entry (screening visit);
  • legally capable to give their consent to participate the study, and available to sign and date the written informed consent prior to the inclusion in the study;
  • women of childbearing potential must agree not to start a pregnancy from the signature of the informed consent up to 30 days after the last administration of the investigational product.

Exclusion Criteria:

  • participation in another trial involving any investigational drug during the past 60 days;
  • known hypersensitivity to venlafaxine or trazodone or their excipients;
  • use of venlafaxine or trazodone within the previous six months;
  • acute, or chronic, or recurrent medical conditions that might affect/jeopardize the study results;
  • significant liver disease, defined as active hepatitis or elevated liver enzymes > 3 times the upper boundary of the normal range;
  • significant renal disease, defined as urea and/or creatinine > 3 times the upper boundary of the normal range
  • myocardial infarction within 6 months prior to start of the double blind treatment;
  • positive present history of glaucoma;
  • history of risk factors for Torsade de Pointes, such as heart failure, cardiac arrhythmias, bradycardia, cardiac conduction abnormalities, family history of long QT syndrome, cardiac hypertrophy, cardiomyopathy, chronic cardiac insufficiency;
  • values of electrolytes (sodium, potassium, calcium, magnesium, chloride) outside the normal laboratory range and judged clinically relevant by the Investigator;
  • concomitant treatment with drugs known for QT prolongation, or with drugs producing hypokalemia, or diuretics;
  • QTcF values higher than 450 msec in the ECG performed at the screening;
  • history of major depression resistant to medical treatments (previous failure to respond to two consecutive antidepressants of different classes used for a sufficient length of time at appropriate doses);
  • history of seizure events other than a single childhood febrile seizure;
  • history of alcohol or psychoactive substance abuse or addiction (except caffeine or nicotine) during the last year as defined by DSM-IV criteria;
  • positive urine drug screen for CNS-active drugs (cocaine, opioids, amphetamines and cannabinoids) at Visit 1 (screening);
  • acute risk of suicide (HAMD, criterion 3 with a value > 3);
  • presence of any primary psychiatric disorder other than major depression;
  • history or presence of bipolar disorder, any psychotic disorder, mental disorder due to general medical conditions;
  • pregnancy, lactation, or female with a positive urine pregnancy test result at Visit 1 (Screening);
  • electroconvulsive therapy (ECT) within 30 days prior to the screening visit;
  • use of antipsychotic drugs within two months prior to the baseline visit (Visit 2);
  • use of any anxiolytic or sedative hypnotic drug within seven days prior to the baseline (Visit 2) and during the study. Exception is stable low doses of benzodiazepines for insomnia (if taken by the patient more than two weeks before the Treatment Phase);
  • use of any psychotropic drug or substance with central nervous system effects within seven days prior to the baseline visit (Visit 2);
  • use of any non-psychotropic drug with psychotropic effects (e.g. alpha-adrenergic blockers) within seven days prior to the baseline visit (visit 2), unless a stable dose of the drug has been maintained for at least one month (three months for thyroid or hormonal medications) before the baseline visit (visit 2);
  • concomitant treatment with CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, indinavir);
  • hyperthyroidism, even if pharmacologically corrected;
  • start or discontinuation of psychotherapy within 6 weeks prior to screening;
  • clinically significant abnormalities on physical examination, vital signs, ECG, laboratory tests at the screening visit;
  • high blood pressure (supine systolic blood pressure > 160 mmHg or supine diastolic blood pressure > 90 mmHg) at screening or baseline, either untreated or under treatment with antihypertensives
  • inability to comply with the protocol requirements, instructions and study-related restrictions; e.g. uncooperative attitude, inability to return for study-visits, and improbability of completing the clinical study;
  • vulnerable subjects (e.g. persons kept in detention);
  • if subject is the Investigator or his/her deputies, first grade relative, research assistant, pharmacist, study coordinator, other staff of relative thereof directly involved in the conduct of the study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02086929


Locations
Austria
Institute für Psychosomatik
Vienna, Austria, 1010
AKH Wien
Vienna, Austria, 1090
Czech Republic
PRAGTIS, s.r.o.
Praha 2, Praha, Czech Republic, 12000
Psychiatry Trial, s.r.o.
Praha 5, Praha, Czech Republic, 15800
MEDICAL SERVICES PRAGUE, s.r.o.
Praha 6, Praha, Czech Republic, 160 00
Neuropsychiatrie s.r.o.
Praha 6, Praha, Czech Republic, 160 00
Saint Anne, s.r.o.
Brno-mesto, Czech Republic, 60200
SUPERVIZE, s.r.o.
Kutna Hora, Czech Republic, 284 01
BIALBI s.r.o.
Litomerice, Czech Republic, 41201
Fakultni Nemocnice Olomouc, Klinika Psychiatrie
Olomouc, Czech Republic, 77 900
MUDr. Eva Soukupová-Psychiatrická praxe, s.r.o.
Plzeň, Czech Republic, 301 00
NZZ- MUDr. Jaroslav Hronek, psychiatrická ambulance
Plzeň, Czech Republic, 301 00
Italy
UOPI di Psichiatria Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele, Presidio "Gaspare Rodolico"
Catania, Italy, 95100
Clinica Psichiatrica Nuovo Ospedale S. Salvatore Università degli Studi del L'Aquila
L'Aquila, Italy, 67100
Ospedale Santa Maria della Misericordia Unità di Degenza Psichiatrica-SPDC
Perugia, Italy, 06132
Azienda Ospedaliera Sant'Andrea Università La Sapienza Unità Operativa Complessa di Psichiatria
Rome, Italy, 00189
AOUS-Azienda Ospedaliera Universitaria Senese Policlinico Santa Maria alle Scotte Clinica Psichiatrica Universitaria
Siena, Italy, 53100
Department of Neurosciences University of Turin
Turin, Italy, 10126
Romania
Quantum Medical Center Srl
Bucharest, Romania, RO-011426
Spitalul clinic de psihiatrie "Prof. Dr. Al. Obregia"/Sectia 13
Bucharest, Romania, RO-041914
Spitalul Clinic de Psihiatrie "Prof. Dr. Al. Obregia"/Sectia 1
Bucharest, Romania, RO-041914
Spitalul Clinc de Urgenta Militar "Dr. Stefan Odobleja", Craiova
Craiova, Romania, RO-200530
Spital Clinic de Psihiatrie SOCOLA / Iasi
Iasi, Romania, RO-700282
Spitalul de Psihiatrie "Dr. Gh.Preda" Sibiu
Sibiu, Romania, RO-550082
Spitalul Clinc Judetean Mures, Centrul de Sanatate Mintala
Targu Mures, Romania, RO-540096
Slovakia
Psychiatricka ambulancia
Bratislava, Slovakia, 81107
MENTUM, s.r.o.
Bratislava, Slovakia, 82007
EPAMED, s.r.o.
Kosice, Slovakia, 4000
Psychiatricka nemocnica
Michalovce, Slovakia, 7101
Psycholine, s.r.o.
Rimavska Sobota, Slovakia, 97901
Psychiatricke oddelenie, NsP sv Barbory Roznava
Roznava, Slovakia, 4801
Spain
Instituto de Investigacion y Asistencia Psiquiatrica - IIAP
Madrid, Spain, 28002
Sponsors and Collaborators
Aziende Chimiche Riunite Angelini Francesco S.p.A
Investigators
Principal Investigator: Filippo Bogetto, MD Department of Neuroscience University of Turin - Italy

Additional Information:
Responsible Party: Aziende Chimiche Riunite Angelini Francesco S.p.A
ClinicalTrials.gov Identifier: NCT02086929     History of Changes
Other Study ID Numbers: 039(C)SC11063
First Posted: March 13, 2014    Key Record Dates
Last Update Posted: December 30, 2015
Last Verified: December 2015

Keywords provided by Aziende Chimiche Riunite Angelini Francesco S.p.A:
Trazodone
Venlafaxine
Major depressive disorder

Additional relevant MeSH terms:
Depressive Disorder
Depression
Depressive Disorder, Major
Disease
Pathologic Processes
Mood Disorders
Mental Disorders
Behavioral Symptoms
Venlafaxine Hydrochloride
Trazodone
Serotonin and Noradrenaline Reuptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Physiological Effects of Drugs
Antidepressive Agents, Second-Generation
Antidepressive Agents
Psychotropic Drugs
Anti-Anxiety Agents
Tranquilizing Agents
Central Nervous System Depressants
Serotonin Uptake Inhibitors
Serotonin Agents