Clinical trial NCT04763135: Mirtazapine in Cancer-related Poly-symptomatology
Official title: What is the Effectiveness and Safety of Mirtazapine Versus Escitalopram in Alleviating Cancer-associated Poly-symptomatology (MIR-P)? A Mixed-method Randomized Controlled Trial Protocol
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Cancer
Neoplasms
Neoplasm Metastasis
Keywords: Cancer
Symptom management
Poly-Symptomatology
Mirtazapine
Antidepressive drugs
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-02-21
Enrollment: 1
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Multicenter, prospective, randomized, controlled trial based on a mixed-method methodology using parallel groups, of oral mirtazapine (intervention) compared with oral escitalopram (control), with a 56 days follow-up. Improvement of the Global health Status (issued from the EORTC-QLQ-C30 (Quality of Life Questionnaire)) will be used as the primary outcome on day 56. Semi-structures interviews will be performed on a purposive sample for qualitative analysis. The 418 participants will be followed-up at day 7, 14, 28 and 56 for a 56 days period. A sub-group of participants will be invited to take part into qualitative interviews at baseline and day 56. Recruitment of participants to the qualitative part will be based on a purposive sampling.


Eligibility criteria: Inclusion Criteria:

* Being over 18 years old
* Suffering from advanced cancer
* Having a clinically estimated life expectancy over 3 months.
* Being diagnosed from having a depressive syndrome by a Hospital Anxiety and Depression Scale-D over 11.
* Being in need of an antidepressant treatment.
* Suffering from at least one under-controlled symptom (defined as a score over 3 on the Edmonton Symptom Assessment Scale) among: pain, nausea, vomiting, breathlessness, lack of appetite, sleep disorders, anxiety or impaired wellbeing.
* Having or not a cancer treatment.
* Being able to understand the information related to the study, and to sign informed consent.
* Having agreed to take part to the study.
* Being able to fill Patient Reported Outcomes questionnaires.
* Being available to be call on days 7 and 14.
* Having a social security affiliation.

Exclusion Criteria:

* Being treated by an antidepressive agent during the four weeks before inclusion.
* Having had a hypersensitivity event to mirtazapine, escitalopram of any excipient.
* Having had a prior inefficient treatment by mirtazapine or escitalopram.
* Having postural hypotension or arterial systolic hypotension inferior to 90 mmHg measured following the guidelines of the European Society of Cardiology
* Having a QT interval over 420 ms.
* Having uncontrolled hearth rhythm disorder or uncontrolled conduction disorder.
* Having had or having bipolar disorder.
* Having uncontrolled seizure or epilepsy (relative non-inclusion criteria needing a neurology specialist opinion)
* Having or having history of closed-angle glaucoma.
* Having bone marrow aplasia.
* Practicing breast-feeding or being pregnant.
* Women of childbearing age with no contraception method.
* Having a treatment with:
* Monoamine oxidase inhibitors (Selegiline, Moclobemide, Isocarboxazid, Nialamide, Phenelzine, Tranylcypromine, Iproniazid, Iproclozide, Toloxatone, Linezolid, Safinamide, Rasagiline)
* One of the following antiarrhythmic drugs: Flecainide, Propafenone, any class IA and III antiarrhythmic drug (amiodarone, disopyramide, hydroquinidine, quinidine, procainamide, sparteine, ajmaline, prajmaline, lorajmine, bretylium tosilate, bunaftine, dofetilide, ibutilide, tedisamil, dronedarone).
* Linezolid, sparfloxacin, moxifloxacin, macrolides (IV erythromycin, josamycin, clarithromycin, telithromycin), pentamidin, halofantrine, HIV protease inhibitors (ritonavir, nelfinavir, amprenavir, indinavir), azolic antifungal agents (ketoconazole, itraconazole, miconazole, fluconazole, voriconazole)
* Mizolastine and Astémizole
* St. John's wort
* Having genetic galactose intolerance or glucose-galactose malabsorption.
* Having one of the following electrolyte disorders not corrected at the time of inclusion: hyponatremia, hyperkalemia, hypokalemia, hypermagnesemia, and hypomagnesemia.
* Having end-stage renal disease with a creatinine clearance inferior to 15 ml/min calculated using the Cockroft's formula.
* Having hepatic failure.
* Having legal incapacity

Primary outcomes:
measure: Global health status score
timeFrame: At baseline and day 56
Secondary outcomes:
measure: The subjective experience associated with symptoms burden.
timeFrame: At baseline and day 56.
measure: Proportion of mitigated symptoms.
timeFrame: Day 28
measure: Proportion of mitigated symptoms.
timeFrame: Day 56
measure: Auto-assessment depression score.
timeFrame: Day 28
measure: Auto-assessment depression score.
timeFrame: Day 56
measure: Hetero-assessment-based depression score.
timeFrame: Day 28
measure: Hetero-assessment-based depression score.
timeFrame: Day 56
measure: Weight control
timeFrame: Day 28
measure: Weight control
timeFrame: Day 56
measure: Weight improvement.
timeFrame: Day 28
measure: Weight improvement.
timeFrame: Day 56
measure: Stability in oral morphine milligram equivalents.
timeFrame: Day 28
measure: Stability in oral morphine milligram equivalents.
timeFrame: Day 56
measure: Escalation in symptom control treatment doses
timeFrame: Day 28
measure: Escalation in symptom control treatment doses
timeFrame: Day 56
measure: Number of side effects.
timeFrame: Day 7
measure: Number of side effects.
timeFrame: Day 14
measure: Number of side effects.
timeFrame: Day 28
measure: Number of side effects.
timeFrame: Day 56
measure: Medication adherence.
timeFrame: Day 56
measure: Symptoms' intensities auto-assessment on the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.
timeFrame: Day 28
measure: Symptoms' intensities auto-assessment on the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.
timeFrame: Day 56
Other outcomes:
Locations:
city: Cébazat
country: France
facility: Centre Hospitalier Universitaire de Clermont-Ferrand
city: La Tronche
country: France
facility: Centre Hospitalier Universitaire de Grenoble
city: Lyon
country: France
facility: Hôpital Edouard Herriot
city: Lyon
country: France
facility: Hôpital de la Croix-Rousse
city: Lyon
country: France
facility: Centre Médico-Chirurgical de Réadaptation des Massues Croix-Rouge française
city: Lyon
country: France
facility: Centre Léon Bérard
city: Paris
country: France
facility: Institut Curie
city: Pierre-Bénite
country: France
facility: Centre Hospitalier Lyon Sud
city: Saint-Étienne
country: France
facility: Centre Hospitalier Universitaire de Saint-Etienne
city: Strasbourg
country: France
facility: Hôpitaux universitaires de Strasbourg
city: Valence
country: France
facility: Centre Hospitalier de Valence
Study officials:
affiliation: Centre Hospitalier Lyon Sud - Service de Soins Palliatifs
name: Guillaume ECONOMOS, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Economos G, Alexandre M, Perceau-Chambard E, Villeneuve L, Subtil F, Haesebaert J, Glehen O. What is the effectiveness and safety of mirtazapine versus escitalopram in alleviating cancer-associated poly-symptomatology (the MIR-P study)? A mixed-method randomized controlled trial protocol. BMC Palliat Care. 2022 May 23;21(1):84. doi: 10.1186/s12904-022-00976-7.