Oral Melatonin in Critically Ill High-risk Patients

Critically Ill Patients Clinical Trial

Official title:

Randomized, Controlled, Double Blind Trial to Evaluate Sedation and Quality of Life in High-risk, Critically Ill Patients Treated With Oral Melatonin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00470821
• Other study ID #: Mela-UniMi-0001
• Status: Completed
• Phase: Phase 4
• First received: May 4, 2007
• Last updated: July 26, 2010
• Start date: May 2007
• Est. completion date: May 2010

Study information

• Verified date: January 2010
• Source: University of Milan
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial Summary

Sleep disruptions are extremely common in high-risk critically ill patients. The investigators want to analyse oral melatonin potentialities as a sedative and a free-radicals scavenger for critically ill patients, and secondarily for preventing Delirium during their ICU stay and post-traumatic stress disorders after ICU discharge.

Description:

The physiological secretion of such melatonin follows a circadian rhythm: melatonin plasma concentration increases with the dark reaching a peak around to midnight and then gradually decreases (Reiter, 1996; Shigeta et al., 2001; Kunz et al., 2004; Brzezinski et al., 2005).

Administration of oral melatonin could be useful in critically ill high-risk patients in Intensive Care Units because these patients are often suffering from sleep disturbances (Weber et al., 1985; Bourne and Mills, 2004) possibly because of:

• presence of underlying pathology with pain and anxiety,

• presence of oral or nasal respiratory prosthesis,

• execution of therapeutic procedures on 24 h. Moreover it has been demonstrated that in ICU patients melatonin rhythm is desynchronized (Bourne and Mills, 2000). This is probably related to sedation and-or mechanical ventilation. Furthermore, it has been showed that melatonin is a powerful anti-oxidant, therefore it could be potentially useful in critical patients usually characterized by increased production of oxygen free radicals.

AIM OF THE STUDY The study is aimed to estimate if the administration of oral melatonin in ICU patients is able to regularize the sleep-waking rhythm, improving sleep quality and reducing episodes of agitation/mental confusion. The main objectives are: assessment of sleep quality, prevalence of mental confusion/agitation, amount of daily sedative drugs administered and modification of redox status.

ENROLLMENT OF PATIENTS At the admission in ICU, obtained the informed consent, the patients will be randomly assigned to the "Treatment" group receiving melatonin 3mg BID by oral route (or nasogastric tube) or to the "Control" group receiving placebo. The sedation will be performed according to clinical standard.

EXPERIMENTAL PROTOCOLS

The following parameters will be monitored:

• epidemiological data,

• quality of the sleep estimated by wrist actigraphy,

• EEG profile on 24h in order to estimate the distribution of sleep phases,

• diurnal and nocturnal hours of sleep,

• total amount of sedative drugs during 24 hours, particularly during nocturnal sedation,

• assessment of sedation level (RASS) (Sessler et al., 2002; Ely et al., 2003),

• episodes of psychomotor agitation and mental confusion (CAM-ICU) (Ely, 2001; 2004),

• evaluation of blood redox state (GSH, GSSG, GSH/GSSG),

• adverse events.

AT THE DISCHARGE FROM ICU, evaluation of:

• SCID-I and SCID-II (Structured Clinical Interview for DSM),

• CAPS (Clinician Administered PTSD Scales),

• HAM-A and HAM-D (Hamilton Rating Scales for Anxiety and for Depression),

• completion of the module for the stressors in ICU and for the transcription of the dreams.

3 MONTHS AFTER DISCHARGE FROM ICU, evaluation of:

• SCID-I and II,

• CAPS,

• HAM-A and HAM-D,

• TAT (Thematic Apperception Test),

• completion of the module for the stressors in ICU and for the transcription of the dreams.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 96
• Est. completion date: May 2010
• Est. primary completion date: April 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 85 Years

Eligibility

Inclusion Criteria:

• High Treatment > 1 day

• Normal gastrointestinal function

Exclusion Criteria:

• Status asthmaticus

• Chronic renal failure under dialytic treatment

• Severe hepatopathy (Child-Pugh class = C)

• Comatous patients (GCS < 12)

• Head trauma, severe neurological diseases (ictus cerebri, SAH, ...)

• Intoxicated patients

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Critical Illness
• Critically Ill Patients
• Mechanically Ventilated Patients

Intervention

Drug:
• Oral melatonin 3mg BID
Identical tablets containing melatonin 3 mg. Nurses are requested to give two tablets daily, at 8 PM and 12 PM
• Placebo
Identical tablets without the active principles. Each evening nurses are requested to give 2 tablets at 8 PM and 12 PM

Locations

Country	Name	City	State
Italy	Azienda Ospedaliera San Paolo - Polo Universitario	Milano

Sponsors (1)

Lead Sponsor	Collaborator
University of Milan

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall sedatives daily doses		Discharge from ICU	No
Secondary	Prevalence of Delirium assessed with CAM-ICU		Discharge from ICU	No
Secondary	Prevalence of mental disorders		60 days after ICU discharge	No
Secondary	ICU length of stay		Discharge from ICU	No
Secondary	ICU mortality		Discharge from ICU	No
Secondary	Hospital mortality		Hospital discharge	No
Secondary	Sleep quantity assessed by wrist actigraphy		Discharge from ICU	Yes