Mirtazapine in Cancer-related Poly-symptomatology (MIR-P)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.

ClinicalTrials.gov Identifier: NCT04763135

Recruitment Status : Not yet recruiting

First Posted : February 21, 2021

Last Update Posted : February 21, 2021

See Contacts and Locations

Sponsor:

Information provided by (Responsible Party):

Hospices Civils de Lyon

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cancer Neoplasms Neoplasm Metastasis	Drug: Mirtazapine Drug: Escitalopram	Phase 3

Study Design

Layout table for study information

Study Type :	Interventional (Clinical Trial)
Estimated Enrollment :	418 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
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
Estimated Study Start Date :	March 8, 2021
Estimated Primary Completion Date :	May 8, 2023
Estimated Study Completion Date :	May 8, 2023

Resource links provided by the National Library of Medicine

Drug Information available for: Citalopram hydrobromide Citalopram Mirtazapine Escitalopram Escitalopram oxalate

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Experimental: Oral mirtazapine Arm 1 patients will be treated using a daily mirtazapine treatment. Treatment will be taken on the evening. Treatment will be initiated at 15 mg daily and gradually increased depending on symptom control and side effects. Treatment doses will be adapted for old patients and those with liver failure.	Drug: Mirtazapine Orally disintegrating tablets of mirtazapine introduced at the dose of 15 mg and increased up to 45 mg per day during 56 days. Doses escalation: based on symptom management and side effect assessment.
Active Comparator: Oral escitalopram Arm 2 patients will be treated using a daily escitalopram treatment. Treatment will be taken in the morning. Treatment will be initiated at 10 mg daily and gradually increased depending on symptom control and side effects. Treatment doses will be adapted for 5 mg for old patients.	Drug: Escitalopram Orally disintegrating tablets of escitalopram introduced at the dose of 10 mg (or 5 mg for patients older than 65) and increased up to 20 mg per day during 56 days. Doses escalation: based on symptom management and side effect assessment.

Outcome Measures

Primary Outcome Measures :

Global health status score [ Time Frame: At baseline and day 56 ]
The Global Health Status will be calculated from the specific subscale included in the EORTC-QLQ-C30 scale.

The difference between baseline and the end-point (day 56) will be the primary judgment criteria. A 4 to 8 points difference between baseline and endpoint will be considered as a mild difference, and a difference over 8 points will be considered as a moderate difference.

Secondary Outcome Measures :

The subjective experience associated with symptoms burden. [ Time Frame: At baseline and day 56. ]
Qualitative analysis of compared semi-structured interviews undertaken at baseline and day 56 on a convenience sample.
Proportion of mitigated symptoms. [ Time Frame: Day 28 ]
The Edmonton Symptom Assessment Scale 12F will be used to assess each symptoms intensities for the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

For each symptom, the difference between baseline and the assessment time will be calculated. A difference equal or over one point will be regarded as mitigation. The judgment criteria will be the proportion of symptoms that were rated over three at baseline and that were mitigated at the assessment time.
Proportion of mitigated symptoms. [ Time Frame: Day 56 ]
The Edmonton Symptom Assessment Scale 12F will be used to assess each symptoms intensities for the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

For each symptom, the difference between baseline and the assessment time will be calculated. A difference equal or over one point will be regarded as mitigation. The judgment criteria will be the proportion of symptoms that were rated over three at baseline and that were mitigated at the assessment time.
Auto-assessment depression score. [ Time Frame: Day 28 ]
The Hospital Anxiety and Depression Scale-D auto-assessment score will be used to assess the auto-assessment depression score.

The judgment criteria will be the difference between baseline and the assessment time. A difference over 1.5 points will be regarded as clinically significant.
Auto-assessment depression score. [ Time Frame: Day 56 ]
The Hospital Anxiety and Depression Scale-D auto-assessment score will be used to assess the auto-assessment depression score.

The judgment criteria will be the difference between baseline and the assessment time. A difference over 1.5 points will be regarded as clinically significant.
Hetero-assessment-based depression score. [ Time Frame: Day 28 ]
The Montgomery-Asberg Depression Rating Scale hetero-assessment score will be used to assess the hetero-assessment depression score.

The judgment criteria will be the difference between baseline and the assessment time. A difference over 1.9 points will be regarded as clinically significant.
Hetero-assessment-based depression score. [ Time Frame: Day 56 ]
The Montgomery-Asberg Depression Rating Scale hetero-assessment score will be used to assess the hetero-assessment depression score.

The judgment criteria will be the difference between baseline and the assessment time. A difference over 1.9 points will be regarded as clinically significant.
Proportion of improvement in functioning sub-scales. [ Time Frame: Day 28 ]
The cognitive functioning, physical functioning, emotional functioning, and role functioning sub-scales issued from the EORTC-QLQ-C30 will be used.

For the cognitive functioning sub-scale, a difference over 3 points will be considered as clinically significant.

For the physical functioning subscale, a difference over 2 points will be considered as clinically significant.

For the emotional functioning subscale, a difference over 6 points will be considered as clinically significant.

For the social functioning subscale, a difference over 6 points will be considered as clinically significant.

The judgment criteria will be the proportion of patients that improved their functioning score.

The judgment criteria will be assessed for each subscale independently.
Proportion of improvement in functioning sub-scales. [ Time Frame: Day 56 ]
The cognitive functioning, physical functioning, emotional functioning, and role functioning sub-scales issued from the EORTC-QLQ-C30 will be used.

For the cognitive functioning sub-scale, a difference over 3 points will be considered as clinically significant.

For the physical functioning subscale, a difference over 2 points will be considered as clinically significant.

For the emotional functioning subscale, a difference over 6 points will be considered as clinically significant.

For the social functioning subscale, a difference over 6 points will be considered as clinically significant.

The judgment criteria will be the proportion of patients that improved their functioning score.

The judgment criteria will be assessed for each subscale independently.
Weight control [ Time Frame: Day 28 ]
Weight control will be defined as a difference under 500g between the weight at baseline minus the weight at the assessment time.

The judgment criteria will be the proportion of patients with weight control at assessment time.
Weight control [ Time Frame: Day 56 ]
Weight control will be defined as a difference under 500g between the weight at baseline minus the weight at the assessment time.

The judgment criteria will be the proportion of patients with weight control at assessment time.
Weight improvement. [ Time Frame: Day 28 ]
Weight improvement will be defined as a difference over 500g between the weight at the assessment time minus the weight at baseline.

The judgment criteria will be the proportion of patients with weight improvement at assessment time.
Weight improvement. [ Time Frame: Day 56 ]
Weight improvement will be defined as a difference over 500g between the weight at the assessment time minus the weight at baseline.

The judgment criteria will be the proportion of patients with weight improvement at assessment time.
Stability in oral morphine milligram equivalents. [ Time Frame: Day 28 ]
The stability in oral morphine milligrams equivalent will be defined as a decrease or stability in the daily doses of opioid pain killers measured using oral morphine milligram equivalents.

The judgment criteria will be the proportion of patients with stability in oral morphine milligram equivalents.
Stability in oral morphine milligram equivalents. [ Time Frame: Day 56 ]
The stability in oral morphine milligrams equivalent will be defined as a decrease or stability in the daily doses of opioid pain killers measured using oral morphine milligram equivalents.

The judgment criteria will be the proportion of patients with stability in oral morphine milligram equivalents.
Escalation in symptom control treatment doses [ Time Frame: Day 28 ]
Escalation in symptom control treatment doses will be defined as any escalation in the dose of a treatment existing at baseline or any new treatment introduced to control one of the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

The judgment criteria will be the proportion of patients with an escalation in symptom control treatment doses.
Escalation in symptom control treatment doses [ Time Frame: Day 56 ]
Escalation in symptom control treatment doses will be defined as any escalation in the dose of a treatment existing at baseline or any new treatment introduced to control one of the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

The judgment criteria will be the proportion of patients with an escalation in symptom control treatment doses.
Number of side effects. [ Time Frame: Day 7 ]
The number of side effects will be used to assess the security of use. It will be assessed using the Antidepressant Side Effect Checklist and side effects will be considered if rated moderate or severe.
Number of side effects. [ Time Frame: Day 14 ]
The number of side effects will be used to assess the security of use. It will be assessed using the Antidepressant Side Effect Checklist and side effects will be considered if rated moderate or severe.
Number of side effects. [ Time Frame: Day 28 ]
The number of side effects will be used to assess the security of use. It will be assessed using the Antidepressant Side Effect Checklist and side effects will be considered if rated moderate or severe.
Number of side effects. [ Time Frame: Day 56 ]
The number of side effects will be used to assess the security of use. It will be assessed using the Antidepressant Side Effect Checklist and side effects will be considered if rated moderate or severe.
Medication adherence. [ Time Frame: Day 56 ]
The medication adherence will be assessed using the Medication Adherence Rating Scale score at day 56 and the Proportion of Days Covered all along the follow-up period.
Symptoms' intensities auto-assessment on the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness. [ Time Frame: Day 28 ]
The Edmonton Symptom Assessment Scale 12F will be used to assess each symptoms intensities for the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

For each symptom, the difference between baseline and the assessment time will be used as the judgment criteria. A difference equal or over one point will be regarded as clinically significant.
Symptoms' intensities auto-assessment on the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness. [ Time Frame: Day 56 ]
The Edmonton Symptom Assessment Scale 12F will be used to assess each symptoms intensities for the following symptoms: pain, nausea, vomiting, lack of appetite, breathlessness, depression, anxiety, sleep disorders and wellness.

For each symptom, the difference between baseline and the assessment time will be used as the judgment criteria. A difference equal or over one point will be regarded as clinically significant.

Eligibility Criteria

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

Layout table for eligibility information

Ages Eligible for Study:	18 Years and older (Adult, Older Adult)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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).
Antipsychotic drugs (phenothiazine antipsychotics, pimozide, haloperidol)
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 Cimetidine
Ticlopidine
Metoprolol
Methadone
Ketamine
Triptan drugs
Dapoxetine
St. John's wort
Antidepressant drug
Any other medication known to cause prolonged QT intervals.
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

Contacts and Locations

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): NCT04763135

Contacts

Layout table for location contacts

Contact: Guillaume ECONOMOS, MD	06.68.05.71.46 ext +33	Guillaume.economos@chu-lyon.fr
Contact: Elise PERCEAU-CHAMBARD, MD	04.78.86.41.48 ext +33	elise.perceau-chambard@chu-lyon.fr

Locations

Layout table for location information

France
Centre Hospitalier Universitaire de Clermont-Ferrand
Cébazat, France, 63118
Contact: Virginie Guastella, MD 04.73.75.09.60 ext +33 Vguastella@chu-clermontferrand.fr
Principal Investigator: Virginie Guastella, MD
Centre Hospitalier Universitaire de Grenoble
La Tronche, France, 38700
Contact: Cécile Barbaret, MD 04.76.76.56.67 ext +33 Cbarbaret@chu-grenoble.fr
Principal Investigator: Cécile Barbaret, MD
Hôpital Edouard Herriot
Lyon, France, 69003
Contact: Sophie Francioni, MD 04.72.11.96.08 ext +33 Sophie.francioni@chu-lyon.fr
Principal Investigator: Sophie Francioni, MD
Hôpital de la Croix-Rousse
Lyon, France, 69004
Contact: Myriam Legenne, MD Myriam.legenne@chu-lyon.fr
Principal Investigator: Myriam Legenne, MD
Centre Médico-Chirurgical de Réadaptation des Massues Croix-Rouge française
Lyon, France, 69005
Contact: Fanny Reix, MD 04.72.38.48.58 ext +33
Principal Investigator: Fanny Reix, MD
Centre Léon Bérard
Lyon, France, 69008
Contact: Olivier Renard, MD 04.78.78.26.57 ext +33 olivier.renard@lyon.unicancer.fr
Principal Investigator: Olivier Renard, MD
Institut Curie
Paris, France, 75005
Contact: Carole Bouleuc, MD 01.44.32.46.40 ext +33 Carole.bouleuc@curie.fr
Principal Investigator: Carole Bouleuc, MD
Centre Hospitalier Lyon Sud
Pierre-Bénite, France, 69495
Contact: Colombe Tricou, MD 04.78.86.41.48 ext +33 Colombe.tricou@chu-lyon.fr
Principal Investigator: Colombe Tricou, MD
Centre Hospitalier Universitaire de Saint-Etienne
Saint-Étienne, France, 42100
Contact: Pascale Vassal, MD 04.77.82.81.00 ext +33 Pascale.vassal@chu-st-etienne.fr
Principal Investigator: Pascale Vassal, MD
Hôpitaux universitaires de Strasbourg
Strasbourg, France, 67098
Contact: Laurent Calvel, MD 06.28.07.12.74 ext +33 aurent.calvel@chru-strasbourg.fr
Principal Investigator: Laurent Calvel, MD
Centre Hospitalier de Valence
Valence, France, 26000
Contact: Héloïse Trichard, MD 04.75.75.73.07 ext +33 Htrichard@ch-valence.fr
Principal Investigator: Héloïse Trichard, MD

Sponsors and Collaborators

Hospices Civils de Lyon

Investigators

Layout table for investigator information

Principal Investigator:	Guillaume ECONOMOS, MD	Centre Hospitalier Lyon Sud - Service de Soins Palliatifs

More Information

Layout table for additonal information

Responsible Party:	Hospices Civils de Lyon
ClinicalTrials.gov Identifier:	NCT04763135
Other Study ID Numbers:	69HCL20_0032 2020-002994-90 ( EudraCT Number )
First Posted:	February 21, 2021 Key Record Dates
Last Update Posted:	February 21, 2021
Last Verified:	February 2021

Layout table for additional information

Studies a U.S. FDA-regulated Drug Product:	No
Studies a U.S. FDA-regulated Device Product:	No

Keywords provided by Hospices Civils de Lyon:


Cancer Symptom management Poly-Symptomatology Mirtazapine Antidepressive drugs

Additional relevant MeSH terms:

Layout table for MeSH terms

Neoplasms Neoplasm Metastasis Neoplastic Processes Pathologic Processes Mirtazapine Citalopram Serotonin Uptake Inhibitors Neurotransmitter Uptake Inhibitors Membrane Transport Modulators Molecular Mechanisms of Pharmacological Action Neurotransmitter Agents Serotonin Agents Physiological Effects of Drugs Antidepressive Agents, Second-Generation Antidepressive Agents	Psychotropic Drugs Histamine H1 Antagonists Histamine Antagonists Histamine Agents Anti-Anxiety Agents Tranquilizing Agents Central Nervous System Depressants Adrenergic alpha-2 Receptor Antagonists Adrenergic alpha-Antagonists Adrenergic Antagonists Adrenergic Agents Serotonin 5-HT2 Receptor Antagonists Serotonin Antagonists Serotonin 5-HT3 Receptor Antagonists

To Top