<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03280329</url>
  </required_header>
  <id_info>
    <org_study_id>Musicoterapia</org_study_id>
    <nct_id>NCT03280329</nct_id>
  </id_info>
  <brief_title>Generalized Versus Personalized Music Therapy in the ICU to Reduce Sedation</brief_title>
  <official_title>Music Therapy in the ICU as a Tool to Reduce Neuroactive Drugs: Generalized Versus Personalized Intervention</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Milan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Milan</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Admission to an Intensive Care Unit (ICU) is one of the major causes of stress and both&#xD;
      physical and emotional difficulties for critically ill patients, both because of the illness&#xD;
      that caused the admission and of the ICU nevironment itself. Despite the use of protocols and&#xD;
      tools to evaluate sedation, many patients continue to have high levels of anxiety. An&#xD;
      inadequate treatment of this condition is associated with increased sympathetic activity&#xD;
      which causes dyspnea and an increase in myocardial oxygen consumption. Sedative drugs, on the&#xD;
      other side, may have significant side effects.&#xD;
&#xD;
      In view of this, there is clear need to find new strategies and instruments allowing for the&#xD;
      maximization of critical patients' comfort, by promoting pain, anxiety, stress and agitation&#xD;
      relief and minimising the need of sedative therapy.&#xD;
&#xD;
      The main hypothesis of this study is that the use of music therapy for critically ill&#xD;
      patients can lead to a significant increase of the days free from neuroactive therapy&#xD;
      (analgesics, sedatives, antianxiety meds, antipsychotics) in the first 28 days following&#xD;
      Intensive Care Unit admission. To this purpose, data obtained from 3 groups of patients will&#xD;
      be compared - a group with individual treatment administered by a music therapist and&#xD;
      delivered by headphones, a group with a generalised treatment, through the creation of a&#xD;
      weekly musical program continuously broadcasted in the hospital room, and a control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Introduction The Intensive Care Unit (ICU) is one of the major causes of stress and both&#xD;
      physical and emotional difficulties for patients and their families.&#xD;
&#xD;
      Studies have been conducted in the investigators' and other Intensive Care Units and they set&#xD;
      out to investigate main causes of stress in critical patients; among the most significant&#xD;
      factors were shown to be life saving treatment such as mechanical ventilation, invasive&#xD;
      procedures, restriction of movement, pain and inability to verbally express it, environment&#xD;
      characterized by constant light and sound stimulation, loss of interaction with loved ones&#xD;
      and the staff, and sleep deprivation.&#xD;
&#xD;
      Despite the use of protocols and tools to evaluate sedation, many patients continue to have&#xD;
      high levels of anxiety. An inadequate treatment of this condition is associated with&#xD;
      increased sympathetic activity which causes dyspnea and an increase in myocardial oxygen&#xD;
      consumption.&#xD;
&#xD;
      In view of it, there is clear need to find new strategies and instruments allowing for the&#xD;
      maximization of critical patients' comfort, by promoting pain, anxiety, stress and agitation&#xD;
      relief and minimising the need of sedative therapy.&#xD;
&#xD;
      Among non pharmacological treatment, hypnosis and relaxation techniques, implementation of&#xD;
      communication with patient, music therapy and physical support are shown to be effective (7).&#xD;
&#xD;
      The use of music as a therapeutic complement has been described in literature for a long&#xD;
      time, using a rational selection in musical composition. Music application to obtain health&#xD;
      benefit is defined music therapy.&#xD;
&#xD;
      The main research question which this study aims to answers is music therapy's effectiveness&#xD;
      in reducing analgesics and sedatives need, as well as reducing anxiety and loneliness, and in&#xD;
      re- establishing normal sleep patterns. It should be noted that music brings significant&#xD;
      benefits as there is absence of contraindications and it is immediately usable by everybody.&#xD;
      Italian experiences in the music therapy field in the Intensive Care Unit are low.&#xD;
&#xD;
      With this music therapy project, the investigators intend to build a multifactorial&#xD;
      intervention to reduce stress risk factors of patients and their families, still not applied&#xD;
      in our country.&#xD;
&#xD;
      Rationale&#xD;
&#xD;
      Many factors influence the effectiveness by music therapy: age, gender, cognitive abilities,&#xD;
      stress levels, anxiety, pain, music education, familiarity with a determinate type of music,&#xD;
      individual preferences, and culture are all elements which can modify the effect of certain&#xD;
      music selection on the subject (19, 20). From this, there is the need of individual choice&#xD;
      and careful monitoring of effects that music has on each individual.&#xD;
&#xD;
      Music therapy in the treatment of stress in the Intensive Care Unit&#xD;
&#xD;
      A recent meta analysis (21) reveals that listening to music can cause a reduction of anxiety&#xD;
      levels in mechanically ventilated patients; some studies show, moreover, a reduction of&#xD;
      analgesic and sedative need in response to the application of a music therapy treatment.&#xD;
&#xD;
      Mechanisms underlying music therapy effectiveness A shared theory about the reduction of&#xD;
      anxiety induced by music is that it helps patients to distance their minds from environmental&#xD;
      stress factors to focus on pleasant sounds and calming incentives (8, 22).&#xD;
&#xD;
      The effect of music is extensive, moreover giving patients an aesthetic experience which&#xD;
      offers comfort and peace in a stressful situation. Guided interventions by music therapists&#xD;
      are more effective because music used is adapted to the needs of that determinate moment,&#xD;
      thanks to professional abilities. If music is selected personally by patient, this provides a&#xD;
      major sense of control in the environment, like that of Intensive Unit, where the patient is&#xD;
      almost totally dependent from health workers (23).&#xD;
&#xD;
      From the neuropsychological point of view, it was assumed that music has a relaxing effect&#xD;
      through its impact on central and autonomic nervous system (24- 26); more specifically, its&#xD;
      application determines a deleting effect on the sympathetic system, leading to a reduction of&#xD;
      circulating catecholamines and to lower nervous and muscle stimulation (25,27). Potential&#xD;
      benefits which result are reduction of pain, reduction of blood pressure, heart rate, oxygen&#xD;
      consumption and muscle tension (2).&#xD;
&#xD;
      Hypothesis of the study The hypothesis of this study is that the use of music therapy for&#xD;
      critically ill patients can lead to a significant increase of the days free from neuroactive&#xD;
      therapy (analgesics, sedatives, antianxiety meds, antipsychotics) in the first 28 days&#xD;
      following Intensive Care Unit admission, in absence of statistically significant reduction of&#xD;
      the welfare index of health workers.&#xD;
&#xD;
      All these data are not available in the literature and would represent an undiscussed&#xD;
      advantage in the promotion of welfare in critical patients during recovery in Intensive Care&#xD;
      and at distance from itself; this can also lead to possible significant implications in terms&#xD;
      of a more effective assistance and lower duration of the stay.&#xD;
&#xD;
      Purpose of the study&#xD;
&#xD;
      The present study study has the main purpose of verifying if using music therapy as an&#xD;
      individualised or generalized intervention in hospitalised patients in Intensive Care, in&#xD;
      different cure settings, allows for a reduction of total dose of&#xD;
      analgesics/sedatives/antipsychotics administered. The investigators will analyse if the&#xD;
      proposed intervention of music therapy can have a role in giving the following advantages:&#xD;
&#xD;
        -  increased hours of sleep of patients,&#xD;
&#xD;
        -  reduction of anxiety and psychomotor agitation manifestations,&#xD;
&#xD;
        -  improvement of work welfare,&#xD;
&#xD;
        -  lower grade of anxiety, stress, and post traumatic symptoms of the family,&#xD;
&#xD;
        -  reduction of frequency and duration of physical restraint,&#xD;
&#xD;
        -  practicability of the proposal of generalized music therapy, through the understanding&#xD;
           the frequency in which music is interrupted for reasons of clinical contingency.&#xD;
&#xD;
      To this purpose, data obtained from 3 groups of patients will be compared - a group with&#xD;
      individual treatment, a group with generalised treatment, through the creation of a weekly&#xD;
      musical program, and a control group.&#xD;
&#xD;
      The population in study will be that of patients hospitalised in Intensive Care for variable&#xD;
      aetiologies, which recovery is longer than 3 days.&#xD;
&#xD;
      All without undermine (or even improve) worker welfare, in order to improve physical and&#xD;
      psychological outcome of patients.&#xD;
&#xD;
      Protocol&#xD;
&#xD;
      Randomization and study groups&#xD;
&#xD;
      The 3 groups are:&#xD;
&#xD;
        1. Control: the patients who belong to this group will not be assigned to a regulated music&#xD;
           therapy treatment, thus they will listen to the background sounds (alerts, voices) right&#xD;
           in the Intensive Care environment; radio use will be allowed according to medical/&#xD;
           nursing judgements;&#xD;
&#xD;
        2. Personalised treatment: during a music therapy consultancy, each patient will be&#xD;
           investigated (if possible from the neurological point of view) on musical preferences&#xD;
           and list of possible music will be proposed which will be reproduced for 2 hours at day.&#xD;
           It is specified that this genre of intervention, as far as well described and studied in&#xD;
           literature, does not belong in clinical practice, and therefore earphones for listening&#xD;
           to music are not yet used in our task force.&#xD;
&#xD;
        3. Generalised treatment: it will be carried out through the creation of a 'weekly&#xD;
           playlist' with the following considerations:&#xD;
&#xD;
             1. Daily sound reproduction from 7 am to 11 pm, with 10 minutes break about every 50&#xD;
                minutes of music;&#xD;
&#xD;
             2. Spread through the environment with specifically designated speakers, at a&#xD;
                controlled volume (30-50 dB);&#xD;
&#xD;
             3. Choice of playlist of music both classic and modern, with very easy listening,&#xD;
                selected according to the daily hours to restore circadian rhythm and following&#xD;
                predictable activities of care provided to patients (hygienic care, retail food,&#xD;
                administration other therapies, physiotherapy, visit by relatives, …);&#xD;
&#xD;
             4. Mixing tracks so that there is continuity and fluidity of listening.&#xD;
&#xD;
      Patients will be randomly assigned to the study groups. On the basis that proposed&#xD;
      intervention has environmental nature (in control and music therapy group), patients&#xD;
      respecting inclusion and exclusion criteria to the protocol will be divided according to the&#xD;
      room occupied. The study is configured like a randomized study, not a blind one.&#xD;
&#xD;
      The environment where the study will take place, the departement of Anestesia e Rianimazione&#xD;
      of San Paolo Hospital - University, does not have single box but 3 open rooms, each one with&#xD;
      2 beds, in which single beds are separated by about 5 meters. This logistic issue will not&#xD;
      hinder the study execution since nothing changes with control group patients about sound&#xD;
      environmental management; for personalized music therapy group the use of earphones avoid the&#xD;
      music overlap coming from the other patients; equally for the generalized music therapy, in&#xD;
      view of intervention nature which provides passive exposure of patients to the music&#xD;
      reproduced in the whole environment of the room, the results will not be relatively impacted&#xD;
      by the ward. The 3 rooms are instead well disjoint among themselves, so that music coming&#xD;
      from one hardly can reach the others.&#xD;
&#xD;
      Collected data It will be measured for each patient's' free days from neuroactive drugs and&#xD;
      neuroactive drug total dosage administered. Moreover, the eventual need of use of restraints&#xD;
      for patient safety and duration will be registered.&#xD;
&#xD;
      Once per nursing shift, anxiety levels will be detected, measured with verbal scale number&#xD;
      (VNR), agitation, measured with RASS scale (Richmond Agitation- Sedation Scale), and pain&#xD;
      will be detected with VNR scale or behavioural measures (Behavioral Pain Scale, BPS).&#xD;
&#xD;
      Moreover the hours of sleep declared in medical record will be registered on the basis of&#xD;
      nurse evaluations.&#xD;
&#xD;
      Through semi structured interviews, welfare of the health care workers and relatives will be&#xD;
      investigated as well as the perceived interference of the intervention based on music&#xD;
      therapy; the impact of experience in Intensive Care on the lives of relatives will be&#xD;
      evaluated through a validated questionnaire (SSS- Short Scale for PTSS).&#xD;
&#xD;
      In order to verify the feasibility of the proposal of generalised music therapy, the number&#xD;
      of interruptions of music reproduction will be registered for contingent clinical reasons.&#xD;
&#xD;
      Analysis of data From the data collected, organised in a database in compliance with the&#xD;
      applicable privacy policy (law 196/2003), it will be possible to verify if the use of&#xD;
      personalised and generalised music therapy in patients hospitalized in Intensive Care, in&#xD;
      different care settings, allows for a reduction of total dosage of analgesic/ sedative/&#xD;
      antipsychotic drugs administered.&#xD;
&#xD;
      All the analysis will be centralised at the investigators' institution.&#xD;
&#xD;
      Sample size Assuming the possibility to transform data with Blom method, in order to obtain a&#xD;
      normal distribution and so higher power in equal amplitude sample, and assuming a effect size&#xD;
      of 0.30 and a doubling of the parameter of main outcome (days free from neuroactive drugs&#xD;
      administration) in the 2 groups of intervention compared to the control group, the sample&#xD;
      size required or an effective power of 80% is 53 subjects per group. This sample size is also&#xD;
      sufficient to cover the analysis conducted comparing measurements repeated on the same&#xD;
      patient. To this purpose, a linear model will be used which requires 51 subjects per groups,&#xD;
      assuming a correlation coefficient of 0.5 between measures and a size effect of 0.25. Sizing&#xD;
      was conducted with SAS software.&#xD;
&#xD;
      Statistical analysis Data will be expressed as median (standard deviation) if normally&#xD;
      distributed (Shapiro- Francia test), or like median ( range interquartile) otherwise. Data&#xD;
      will be transcribed from clinical records on a sheet of Microsoft Excel 2010 calculations&#xD;
      (Microsoft Corporation, Redmond, WA, USA). Statistical analysis will be performed with&#xD;
      Stata/SE 12.0 (StataCorp, College Station, TX USA). For each comparison statistical&#xD;
      significance will be considered for values of p&lt;0.05.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">May 1, 2017</start_date>
  <completion_date type="Anticipated">December 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">October 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Neuroactive drug free days</measure>
    <time_frame>one year</time_frame>
    <description>the outcome will be calculated giving one point for each day during the measurement period that patients are both alive and free the administration of any neuroactive drug</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Sedative exposure</measure>
    <time_frame>one year</time_frame>
    <description>Sedative exposure will be determined for all patients who will receivd any of 8 commonly administered sedative and analgesic medications in the ICU (midazolam, lorazepam, propofol, dexmedetomidine, morphine, fentanyl, hydromorphone, haloperidol) 24 hours prior to enrollment and each day during the study. Sedative exposure will be operationalized as a daily sedative drug intensity score and sedative dose frequency</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>reduction of the stress associated to ICU stay</measure>
    <time_frame>one year</time_frame>
    <description>the stress during the ICU stay will be measured by the validated ICUESS scale</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">153</enrollment>
  <condition>Critical Illness</condition>
  <condition>Hypnotics and Sedatives</condition>
  <condition>Music Therapy</condition>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>No Intervention</arm_group_type>
    <description>the patients who belong to this group will not be assigned to a regulated music therapy treatment, thus they will listen to the background sounds (alerts, voices) right in the Intensive Care environment; radio use will be allowed according to medical/ nursing judgements</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Personalised treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A music therapy advice will be performed with each patient (if possible from the neurological point of view) or their caregivers to assess their musical preferences and a list of songs will be generated which will be reproduced for 2 hours per day from admission to discharge with the use of earphones.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Generalized treatment</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Music will be broadcasted in each patient room after the creation of a 'weekly playlist' with the following considerations:&#xD;
Daily sound reproduction from 7 am to 11 pm, with 10 minutes break about every 50 minutes of music;&#xD;
Spread through the environment with specifically designated speakers, at a controlled volume (30-50 dB);&#xD;
Choice of playlist of music both classic and modern, with very easy listening, selected according to the daily hours to restore circadian rhythm and following predictable activities of care provided to patients (hygienic care, retail food, administration other therapies, physiotherapy, visit by relatives, …);&#xD;
Mixing tracks so that there is continuity and fluidity of listening</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Generalized Music therapy</intervention_name>
    <description>Patients will receive broadcasted music via speakers in their room from 7am to 11pm, from admission to discharge</description>
    <arm_group_label>Generalized treatment</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Personalized Music therapy</intervention_name>
    <description>Patients will receive music via earphones after specific music therapist advice, for 2 hours per day, from admission to discharge</description>
    <arm_group_label>Personalised treatment</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  all patients hospitalized in Intensive Care for any medical, surgical traumatic&#xD;
             condition, whose stay in the ICU is expected to be longer than 2 days&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  expected Glascow Goma Scale at ICU discharge lower than 12&#xD;
&#xD;
          -  hearing impairment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>michele umbrello, MD</last_name>
    <phone>+390281844476</phone>
    <email>micheleumbrello@yahoo.it</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ospedale San Paolo - Polo Universitario</name>
      <address>
        <city>Milano</city>
        <zip>20142</zip>
        <country>Italy</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Giovanni Mistraletti, MD</last_name>
      <phone>0039-02-50323134</phone>
      <email>giovanni.mistraletti@unimi.it</email>
    </contact>
    <investigator>
      <last_name>Giovanni Mistraletti, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Michele Umbrello, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Italy</country>
  </location_countries>
  <verification_date>June 2018</verification_date>
  <study_first_submitted>September 7, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <last_update_submitted>June 21, 2018</last_update_submitted>
  <last_update_submitted_qc>June 21, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Milan</investigator_affiliation>
    <investigator_full_name>Giovanni Mistraletti</investigator_full_name>
    <investigator_title>University researcher</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Critical Illness</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03280329
org study id: Musicoterapia
nct id: NCT03280329
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Admission to an Intensive Care Unit (ICU) is one of the major causes of stress and both
      physical and emotional difficulties for critically ill patients, both because of the illness
      that caused the admission and of the ICU nevironment itself. Despite the use of protocols and
      tools to evaluate sedation, many patients continue to have high levels of anxiety. An
      inadequate treatment of this condition is associated with increased sympathetic activity
      which causes dyspnea and an increase in myocardial oxygen consumption. Sedative drugs, on the
      other side, may have significant side effects.

      In view of this, there is clear need to find new strategies and instruments allowing for the
      maximization of critical patients' comfort, by promoting pain, anxiety, stress and agitation
      relief and minimising the need of sedative therapy.

      The main hypothesis of this study is that the use of music therapy for critically ill
      patients can lead to a significant increase of the days free from neuroactive therapy
      (analgesics, sedatives, antianxiety meds, antipsychotics) in the first 28 days following
      Intensive Care Unit admission. To this purpose, data obtained from 3 groups of patients will
      be compared - a group with individual treatment administered by a music therapist and
      delivered by headphones, a group with a generalised treatment, through the creation of a
      weekly musical program continuously broadcasted in the hospital room, and a control group.
Introduction The Intensive Care Unit (ICU) is one of the major causes of stress and both
      physical and emotional difficulties for patients and their families.

      Studies have been conducted in the investigators' and other Intensive Care Units and they set
      out to investigate main causes of stress in critical patients; among the most significant
      factors were shown to be life saving treatment such as mechanical ventilation, invasive
      procedures, restriction of movement, pain and inability to verbally express it, environment
      characterized by constant light and sound stimulation, loss of interaction with loved ones
      and the staff, and sleep deprivation.

      Despite the use of protocols and tools to evaluate sedation, many patients continue to have
      high levels of anxiety. An inadequate treatment of this condition is associated with
      increased sympathetic activity which causes dyspnea and an increase in myocardial oxygen
      consumption.

      In view of it, there is clear need to find new strategies and instruments allowing for the
      maximization of critical patients' comfort, by promoting pain, anxiety, stress and agitation
      relief and minimising the need of sedative therapy.

      Among non pharmacological treatment, hypnosis and relaxation techniques, implementation of
      communication with patient, music therapy and physical support are shown to be effective (7).

      The use of music as a therapeutic complement has been described in literature for a long
      time, using a rational selection in musical composition. Music application to obtain health
      benefit is defined music therapy.

      The main research question which this study aims to answers is music therapy's effectiveness
      in reducing analgesics and sedatives need, as well as reducing anxiety and loneliness, and in
      re- establishing normal sleep patterns. It should be noted that music brings significant
      benefits as there is absence of contraindications and it is immediately usable by everybody.
      Italian experiences in the music therapy field in the Intensive Care Unit are low.

      With this music therapy project, the investigators intend to build a multifactorial
      intervention to reduce stress risk factors of patients and their families, still not applied
      in our country.

      Rationale

      Many factors influence the effectiveness by music therapy: age, gender, cognitive abilities,
      stress levels, anxiety, pain, music education, familiarity with a determinate type of music,
      individual preferences, and culture are all elements which can modify the effect of certain
      music selection on the subject (19, 20). From this, there is the need of individual choice
      and careful monitoring of effects that music has on each individual.

      Music therapy in the treatment of stress in the Intensive Care Unit

      A recent meta analysis (21) reveals that listening to music can cause a reduction of anxiety
      levels in mechanically ventilated patients; some studies show, moreover, a reduction of
      analgesic and sedative need in response to the application of a music therapy treatment.

      Mechanisms underlying music therapy effectiveness A shared theory about the reduction of
      anxiety induced by music is that it helps patients to distance their minds from environmental
      stress factors to focus on pleasant sounds and calming incentives (8, 22).

      The effect of music is extensive, moreover giving patients an aesthetic experience which
      offers comfort and peace in a stressful situation. Guided interventions by music therapists
      are more effective because music used is adapted to the needs of that determinate moment,
      thanks to professional abilities. If music is selected personally by patient, this provides a
      major sense of control in the environment, like that of Intensive Unit, where the patient is
      almost totally dependent from health workers (23).

      From the neuropsychological point of view, it was assumed that music has a relaxing effect
      through its impact on central and autonomic nervous system (24- 26); more specifically, its
      application determines a deleting effect on the sympathetic system, leading to a reduction of
      circulating catecholamines and to lower nervous and muscle stimulation (25,27). Potential
      benefits which result are reduction of pain, reduction of blood pressure, heart rate, oxygen
      consumption and muscle tension (2).

      Hypothesis of the study The hypothesis of this study is that the use of music therapy for
      critically ill patients can lead to a significant increase of the days free from neuroactive
      therapy (analgesics, sedatives, antianxiety meds, antipsychotics) in the first 28 days
      following Intensive Care Unit admission, in absence of statistically significant reduction of
      the welfare index of health workers.

      All these data are not available in the literature and would represent an undiscussed
      advantage in the promotion of welfare in critical patients during recovery in Intensive Care
      and at distance from itself; this can also lead to possible significant implications in terms
      of a more effective assistance and lower duration of the stay.

      Purpose of the study

      The present study study has the main purpose of verifying if using music therapy as an
      individualised or generalized intervention in hospitalised patients in Intensive Care, in
      different cure settings, allows for a reduction of total dose of
      analgesics/sedatives/antipsychotics administered. The investigators will analyse if the
      proposed intervention of music therapy can have a role in giving the following advantages:

        -  increased hours of sleep of patients,

        -  reduction of anxiety and psychomotor agitation manifestations,

        -  improvement of work welfare,

        -  lower grade of anxiety, stress, and post traumatic symptoms of the family,

        -  reduction of frequency and duration of physical restraint,

        -  practicability of the proposal of generalized music therapy, through the understanding
           the frequency in which music is interrupted for reasons of clinical contingency.

      To this purpose, data obtained from 3 groups of patients will be compared - a group with
      individual treatment, a group with generalised treatment, through the creation of a weekly
      musical program, and a control group.

      The population in study will be that of patients hospitalised in Intensive Care for variable
      aetiologies, which recovery is longer than 3 days.

      All without undermine (or even improve) worker welfare, in order to improve physical and
      psychological outcome of patients.

      Protocol

      Randomization and study groups

      The 3 groups are:

        1. Control: the patients who belong to this group will not be assigned to a regulated music
           therapy treatment, thus they will listen to the background sounds (alerts, voices) right
           in the Intensive Care environment; radio use will be allowed according to medical/
           nursing judgements;

        2. Personalised treatment: during a music therapy consultancy, each patient will be
           investigated (if possible from the neurological point of view) on musical preferences
           and list of possible music will be proposed which will be reproduced for 2 hours at day.
           It is specified that this genre of intervention, as far as well described and studied in
           literature, does not belong in clinical practice, and therefore earphones for listening
           to music are not yet used in our task force.

        3. Generalised treatment: it will be carried out through the creation of a 'weekly
           playlist' with the following considerations:

             1. Daily sound reproduction from 7 am to 11 pm, with 10 minutes break about every 50
                minutes of music;

             2. Spread through the environment with specifically designated speakers, at a
                controlled volume (30-50 dB);

             3. Choice of playlist of music both classic and modern, with very easy listening,
                selected according to the daily hours to restore circadian rhythm and following
                predictable activities of care provided to patients (hygienic care, retail food,
                administration other therapies, physiotherapy, visit by relatives, …);

             4. Mixing tracks so that there is continuity and fluidity of listening.

      Patients will be randomly assigned to the study groups. On the basis that proposed
      intervention has environmental nature (in control and music therapy group), patients
      respecting inclusion and exclusion criteria to the protocol will be divided according to the
      room occupied. The study is configured like a randomized study, not a blind one.

      The environment where the study will take place, the departement of Anestesia e Rianimazione
      of San Paolo Hospital - University, does not have single box but 3 open rooms, each one with
      2 beds, in which single beds are separated by about 5 meters. This logistic issue will not
      hinder the study execution since nothing changes with control group patients about sound
      environmental management; for personalized music therapy group the use of earphones avoid the
      music overlap coming from the other patients; equally for the generalized music therapy, in
      view of intervention nature which provides passive exposure of patients to the music
      reproduced in the whole environment of the room, the results will not be relatively impacted
      by the ward. The 3 rooms are instead well disjoint among themselves, so that music coming
      from one hardly can reach the others.

      Collected data It will be measured for each patient's' free days from neuroactive drugs and
      neuroactive drug total dosage administered. Moreover, the eventual need of use of restraints
      for patient safety and duration will be registered.

      Once per nursing shift, anxiety levels will be detected, measured with verbal scale number
      (VNR), agitation, measured with RASS scale (Richmond Agitation- Sedation Scale), and pain
      will be detected with VNR scale or behavioural measures (Behavioral Pain Scale, BPS).

      Moreover the hours of sleep declared in medical record will be registered on the basis of
      nurse evaluations.

      Through semi structured interviews, welfare of the health care workers and relatives will be
      investigated as well as the perceived interference of the intervention based on music
      therapy; the impact of experience in Intensive Care on the lives of relatives will be
      evaluated through a validated questionnaire (SSS- Short Scale for PTSS).

      In order to verify the feasibility of the proposal of generalised music therapy, the number
      of interruptions of music reproduction will be registered for contingent clinical reasons.

      Analysis of data From the data collected, organised in a database in compliance with the
      applicable privacy policy (law 196/2003), it will be possible to verify if the use of
      personalised and generalised music therapy in patients hospitalized in Intensive Care, in
      different care settings, allows for a reduction of total dosage of analgesic/ sedative/
      antipsychotic drugs administered.

      All the analysis will be centralised at the investigators' institution.

      Sample size Assuming the possibility to transform data with Blom method, in order to obtain a
      normal distribution and so higher power in equal amplitude sample, and assuming a effect size
      of 0.30 and a doubling of the parameter of main outcome (days free from neuroactive drugs
      administration) in the 2 groups of intervention compared to the control group, the sample
      size required or an effective power of 80% is 53 subjects per group. This sample size is also
      sufficient to cover the analysis conducted comparing measurements repeated on the same
      patient. To this purpose, a linear model will be used which requires 51 subjects per groups,
      assuming a correlation coefficient of 0.5 between measures and a size effect of 0.25. Sizing
      was conducted with SAS software.

      Statistical analysis Data will be expressed as median (standard deviation) if normally
      distributed (Shapiro- Francia test), or like median ( range interquartile) otherwise. Data
      will be transcribed from clinical records on a sheet of Microsoft Excel 2010 calculations
      (Microsoft Corporation, Redmond, WA, USA). Statistical analysis will be performed with
      Stata/SE 12.0 (StataCorp, College Station, TX USA). For each comparison statistical
      significance will be considered for values of p<0.05.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Neuroactive drug free days
time frame: one year
description: the outcome will be calculated giving one point for each day during the measurement period that patients are both alive and free the administration of any neuroactive drug
measure: Sedative exposure
time frame: one year
description: Sedative exposure will be determined for all patients who will receivd any of 8 commonly administered sedative and analgesic medications in the ICU (midazolam, lorazepam, propofol, dexmedetomidine, morphine, fentanyl, hydromorphone, haloperidol) 24 hours prior to enrollment and each day during the study. Sedative exposure will be operationalized as a daily sedative drug intensity score and sedative dose frequency
measure: reduction of the stress associated to ICU stay
time frame: one year
description: the stress during the ICU stay will be measured by the validated ICUESS scale
arm group label: Control
arm group type: No Intervention
description: the patients who belong to this group will not be assigned to a regulated music therapy treatment, thus they will listen to the background sounds (alerts, voices) right in the Intensive Care environment; radio use will be allowed according to medical/ nursing judgements
arm group label: Personalised treatment
arm group type: Active Comparator
description: A music therapy advice will be performed with each patient (if possible from the neurological point of view) or their caregivers to assess their musical preferences and a list of songs will be generated which will be reproduced for 2 hours per day from admission to discharge with the use of earphones.
arm group label: Generalized treatment
arm group type: Active Comparator
description: Music will be broadcasted in each patient room after the creation of a 'weekly playlist' with the following considerations:
Daily sound reproduction from 7 am to 11 pm, with 10 minutes break about every 50 minutes of music;
Spread through the environment with specifically designated speakers, at a controlled volume (30-50 dB);
Choice of playlist of music both classic and modern, with very easy listening, selected according to the daily hours to restore circadian rhythm and following predictable activities of care provided to patients (hygienic care, retail food, administration other therapies, physiotherapy, visit by relatives, …);
Mixing tracks so that there is continuity and fluidity of listening
intervention type: Other
intervention name: Generalized Music therapy
description: Patients will receive broadcasted music via speakers in their room from 7am to 11pm, from admission to discharge
arm group label: Generalized treatment
intervention type: Other
intervention name: Personalized Music therapy
description: Patients will receive music via earphones after specific music therapist advice, for 2 hours per day, from admission to discharge
arm group label: Personalised treatment
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: michele umbrello, MD
phone: +390281844476
email: micheleumbrello@yahoo.it
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
country: Italy
responsible party type: Principal Investigator
investigator affiliation: University of Milan
investigator full name: Giovanni Mistraletti
investigator title: University researcher
mesh term: Critical Illness