Post-operative DeliriumMINDNCT03785158
MIND After Surgery
A study testing Liquid Melatonin in people with Post-operative Delirium and Major Non-cardiac Surgery, run by McMaster University at 2 sites in Canada.
Trial summary
Delirium is the most common neurological adverse outcome in elderly surgical patients. It is associated with an increased mortality and morbidity, including need for prolonged hospital stay and institutional care. Despite this, there are no effective preventive strategies. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Post-operative Delirium, Major Non-cardiac Surgery
- What is being tested?
- Liquid Melatonin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 88 participants
- Where
- 2 sitesCanada
- Study dates
- 14 Sep 2021to 5 Jul 2025
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Age >65 years
- having a major non-cardiac surgery (which involve major vascular, thoracic, orthopedic, gynecological, otolaryngeal, general and gastrointestinal surgeries) with an expected hospital stay of 2 days or more, and
- ability to provide informed consent
Who cannot join
- active delirium or dementia
- ongoing melatonin treatment
- unable to take oral medications
- planned postoperative ventilation
- previous study participation
- allergy to melatonin
Show all 10Show fewer
- hepatic impairment defined as alanine aminotransferase greater than 500 IU/L
- previous liver transplant or liver cirrhosis of Child-Pugh classes B and C
- not willing to participate
- language barrier
Trial locations and contacts
2 sites in 1 country.
Canada2 sites
St. Joseph's Healthcare Hamilton
Hamilton, Ontario, L8N 4A6
Hamilton Health Sciences-Juravinski Hospital Location
Hamilton, Ontario, L8V 1C3
About this study
Official title: Melatonin for Preventing Postoperative Delirium in Elderly Patients; a Multi-centre Randomized Placebo Controlled Pilot Study
Delirium is the most common neurological adverse outcome in elderly surgical patients. It is associated with an increased mortality and morbidity, including need for prolonged hospital stay and institutional care. Despite this, there are no effective preventive strategies. Melatonin is a hormone released from the pineal gland. It is used to improve sleep quality and to treat jet lag. Small studies have suggested that it can decrease the chances of delirium. Since the existing literature is small and uncertain, it is important to test its benefit in a large sample to help guide clinicians. This proposed trial is aimed at testing assessing the feasibility of a large, multi-center, randomized control trial to decrease the incidence of postoperative delirium.
Read the detailed description
Delirium is defined as an acute and fluctuating disturbance in cognition characterized by alterations in the level of attention and awareness, which develops over a relative short period of time and represents a change from the subject's baseline. Its incidence increases with age and occurs in nearly 50% of elderly inpatients. Postoperative delirium (POD) increases the risk of patient morbidity and mortality and thereby increasing the cost for the health care system. Increased risk of mortality persists even three years after hospitalization, and is an independent risk factor for urinary incontinence, falls, and decubitus ulcers.
A large prospective study of 1341 patients having non-cardiac surgery with a postoperative stay of at least 48 hours, reported an overall incidence of 9% in >50 years and 15% in >70 years. Another recent study involving 566 patients of similar surgical cohort reported an incidence of 24%.
With no current effective treatment, there is a greater focus on prevention of delirium. Approximately 15% of all POD could be preventable. Preventive strategies can be pharmacological and non-pharmacological. Non-pharmacological strategies are multifaceted and involve different interventions. Among attempted pharmacological options, none have really shown much promise and many suffer from associated adverse effects.
Melatonin is a pineal gland hormone that regulates the sleep-wake rhythm. Disruption of the sleep-wake cycle is observed in delirium. Abnormal tryptophan metabolism is hypothesized as a cause for delirium and melatonin supplementation is observed to decrease the breakdown of tryptophan and serotonin through positive feedback. In patients who develop POD, low tryptophan and serum melatonin levels were observed. Other advantages of melatonin, being a natural supplement, include improved sleep, sparing of sedatives, minimal potential for abuse, or hangover effects.
Systematic reviews done with the existing literature specific to melatonin by a literature search of MEDLINE, EMBASE and Cochrane databases for combination of terms "melatonin" and "delirium", restricted to clinical trials and up to October 25, 2017 found one relevant systematic review: this systematic review looked at the use of melatonin for delirium prevention and found four randomized control trials (RCT), out of which three showed positive results and one showed a negative result. Presently, despite its potential to reduce POD and improve sleep, the role of melatonin in the elderly surgical population is uncertain. There is a clear need for a large, well-designed study to establish definitive evidence.
- Conditions
- Post-operative Delirium, Major Non-cardiac Surgery
- Being tested
- Liquid Melatonin, Placebo
- Keywords
- Delirium, Elderly patients having non-cardiac surgery, Melatonin, sleep quality, sleep deprivation, sleep-wake cycle
- Medical subject headings
- Emergence Delirium, Delirium, Sleep Initiation and Maintenance Disorders, Sleep Deprivation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Liquid MelatoninOther
Melatonin is a natural supplement.
PlaceboOther
Similar looking/tasting placebo syrup
| Study group | Role | What they receive |
|---|---|---|
| Melatonin | Active comparator | 3 mg of liquid melatonin by oral route for 8 days. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days. Receives: Other: Liquid Melatonin |
| Placebo Group | Placebo comparator | Similar looking/tasting 3 mg (5 ml) placebo syrup administered preoperatively by oral route and for the next 7 days or until discharge. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days. Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recruitment rate
Recruitment rate: assessed as at least 4-5 patients/week, and completion of recruitment (60 patients/site) in each site over 3-4 months.
Measured: 6 months
Medication compliance
Proportion of patients who are able to take at least two doses of study medications, assessed as >85% of study patients.
Measured: 8 days
Follow up to 3 months
Proportion of patients who complete 3 months follow up. For feasibility we expect >90% patients to complete study follow up.
Measured: 3 months
Proportion of patients recruited from screening
To identify the proportion of screened patients meeting the study inclusion criteria
Measured: 6 months
Secondary outcomes (9)
Incidence of Delirium
This will be captured from observing the patient from the time of their discharge from pre-anesthetic care unit (PACU), until the time of discharge. Presence or absence will be captured using the Confusion Assessment Method (CAM)-short form. If patient is mechanically ventilated, the assessment will be performed using Confusion Assessment Method-Intensive Care Unit (CAM-ICU) tool.
Measured: 8 days
Severity of Delirium
When an episode of post-operative delirium is observed, the severity will be assessed using Confusion Assessment Method (CAM) severity form. We will only record the severity for the first episode of post operative delirium observed.
Measured: 8 days
Sleep quality
Quality of sleep will be assessed daily using Richards-Campbell Sleep Questionnaire (RCSQ). It is a visual analogue scale 0-100mm; zero indicating the worst possible sleep to 100 indicating the best sleep.
Measured: 8 days
Incidence of ICU care
Need for ICU or critical care during hospitalization: This will be captured along with the reason and duration of such a stay from hospital records/patient charts
Measured: 8 days
Prolonged hospital stay
Prolonged hospital stay (beyond anticipated for each patient) will be captured from hospital records/patient charts along with the reason and duration of such a stay
Measured: 8 days
Institutional discharge
This will be recorded from hospital records.
Measured: 3 months
Cognitive Status
This will be captured using Mini Mental Status Examination (MMSE)
Measured: 3 months
Mortality
This outcome will be captured as in-hospital mortality and up to 3 months after discharge.
Measured: 3 months
Adverse effects
Observe significant sedation using Pasero Opioid-induced Sedation Scale (validated, commonly used) S=Sleep, easy to arouse
- Awake and alert
- Slightly drowsy, easily aroused (S, 1, 2 all acceptable; no action necessary; may increase opioid dose if needed)
- Frequently drowsy, arousable, drifts off to sleep during conversation Unacceptable; monitor respiratory status and sedation level closely until sedation level is stable at <3 and respiratory status is satisfactory; decrease opioid dose 25% to 50%, or notifiy prescriber or anesthesiologist for orders; consider a non-sedation, opioid-sparing nonopioid if not contraindicated
- Somnolent, minimal or no response to verbal and physical stimulation Unacceptable; stop opioid; consider administering naloxone; notifiy prescriber or anesthesiologist; monitor respiratory status and sedation level closely until sedation level is stable at <3 and respiratory status is acceptable
Measured: 7 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Dec 2018
- Study start14 Sep 2021
- Primary completion5 Jul 2025
- Study completion5 Jul 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Post-operative DeliriumStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- This is a randomised, placebo-controlled, two arm parallel design pilot RCT
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 88 participants (actual)
Sponsor and investigators
- Lead sponsor
- McMaster University
- Sponsor type
- University, hospital or other
- Collaborators
- St. Joseph's Healthcare Hamilton
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03785158
- Sponsor's protocol ID
- 5506
- Acronym
- MIND
- Status last verified
- Jul 2025
- First submitted
- 20 Dec 2018
- Last updated
- 12 Sep 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Melatonin for Preventing Postoperative Delirium in Elderly Patients; a Multi-centre Randomized Placebo Controlled Pilot Study
- ClinicalTrials.gov ID
- NCT03785158
- Acronym / sponsor ID
- MIND / 5506
- Conditions
- Post-operative Delirium, Major Non-cardiac Surgery
- Keywords
- Delirium, Elderly patients having non-cardiac surgery, Melatonin, sleep quality, sleep deprivation, sleep-wake cycle
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 88 participants (actual)
- Lead sponsor
- McMaster UniversityUniversity, hospital or other
- Collaborators
- St. Joseph's Healthcare Hamilton
- Study start
- 14 Sep 2021 (actual)
- Primary completion
- 5 Jul 2025 (actual)
- Study completion
- 5 Jul 2025 (actual)
- First posted
- 24 Dec 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Delirium is the most common neurological adverse outcome in elderly surgical patients. It is associated with an increased mortality and morbidity, including need for prolonged hospital stay and institutional care. Despite this, there are no effective preventive strategies. Melatonin is a hormone released from the pineal gland. It is used to improve sleep quality and to treat jet lag. Small studies have suggested that it can decrease the chances of delirium. Since the existing literature is small and uncertain, it is important to test its benefit in a large sample to help guide clinicians. This proposed trial is aimed at testing assessing the feasibility of a large, multi-center, randomized control trial to decrease the incidence of postoperative delirium.
Detailed description
Delirium is defined as an acute and fluctuating disturbance in cognition characterized by alterations in the level of attention and awareness, which develops over a relative short period of time and represents a change from the subject's baseline. Its incidence increases with age and occurs in nearly 50% of elderly inpatients. Postoperative delirium (POD) increases the risk of patient morbidity and mortality and thereby increasing the cost for the health care system. Increased risk of mortality persists even three years after hospitalization, and is an independent risk factor for urinary incontinence, falls, and decubitus ulcers.
A large prospective study of 1341 patients having non-cardiac surgery with a postoperative stay of at least 48 hours, reported an overall incidence of 9% in >50 years and 15% in >70 years. Another recent study involving 566 patients of similar surgical cohort reported an incidence of 24%.
With no current effective treatment, there is a greater focus on prevention of delirium. Approximately 15% of all POD could be preventable. Preventive strategies can be pharmacological and non-pharmacological. Non-pharmacological strategies are multifaceted and involve different interventions. Among attempted pharmacological options, none have really shown much promise and many suffer from associated adverse effects.
Melatonin is a pineal gland hormone that regulates the sleep-wake rhythm. Disruption of the sleep-wake cycle is observed in delirium. Abnormal tryptophan metabolism is hypothesized as a cause for delirium and melatonin supplementation is observed to decrease the breakdown of tryptophan and serotonin through positive feedback. In patients who develop POD, low tryptophan and serum melatonin levels were observed. Other advantages of melatonin, being a natural supplement, include improved sleep, sparing of sedatives, minimal potential for abuse, or hangover effects.
Systematic reviews done with the existing literature specific to melatonin by a literature search of MEDLINE, EMBASE and Cochrane databases for combination of terms "melatonin" and "delirium", restricted to clinical trials and up to October 25, 2017 found one relevant systematic review: this systematic review looked at the use of melatonin for delirium prevention and found four randomized control trials (RCT), out of which three showed positive results and one showed a negative result. Presently, despite its potential to reduce POD and improve sleep, the role of melatonin in the elderly surgical population is uncertain. There is a clear need for a large, well-designed study to establish definitive evidence.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- This is a randomised, placebo-controlled, two arm parallel design pilot RCT
| Arm | Type | Receives |
|---|---|---|
| Melatonin | Active comparator | Other: Liquid Melatonin3 mg of liquid melatonin by oral route for 8 days. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days. |
| Placebo Group | Placebo comparator | Other: PlaceboSimilar looking/tasting 3 mg (5 ml) placebo syrup administered preoperatively by oral route and for the next 7 days or until discharge. The 1st dose will be given 1-2 hours prior to the surgery, followed by bed time doses (between 7-9 pm) given on postoperative day (POD) 1 until discharge or for the first 7 days. |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (3 listed)
- Age >65 years
- having a major non-cardiac surgery (which involve major vascular, thoracic, orthopedic, gynecological, otolaryngeal, general and gastrointestinal surgeries) with an expected hospital stay of 2 days or more, and
- ability to provide informed consent
Key exclusion criteria (10 listed)
- active delirium or dementia
- ongoing melatonin treatment
- unable to take oral medications
- planned postoperative ventilation
- previous study participation
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Liquid MelatoninMelatonin is a natural supplement. | Other | Melatonin |
| PlaceboSimilar looking/tasting placebo syrup | Other | Placebo Group |
Primary outcome
Recruitment rate
Time frame: 6 months
Recruitment rate: assessed as at least 4-5 patients/week, and completion of recruitment (60 patients/site) in each site over 3-4 months.
Medication compliance
Time frame: 8 days
Proportion of patients who are able to take at least two doses of study medications, assessed as >85% of study patients.
Follow up to 3 months
Time frame: 3 months
Proportion of patients who complete 3 months follow up. For feasibility we expect >90% patients to complete study follow up.
Proportion of patients recruited from screening
Time frame: 6 months
To identify the proportion of screened patients meeting the study inclusion criteria
9 secondary outcomes
Incidence of Delirium
Time frame: 8 days
Severity of Delirium
Time frame: 8 days
Sleep quality
Time frame: 8 days
Incidence of ICU care
Time frame: 8 days
Prolonged hospital stay
Time frame: 8 days
Institutional discharge
Time frame: 3 months
Cognitive Status
Time frame: 3 months
Mortality
Time frame: 3 months
Adverse effects
Time frame: 7 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Sep 2025.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Liquid Melatonin in people with Post-operative Delirium and Major Non-cardiac Surgery, run by McMaster University at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 12 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Recruitment rate (time frame: 6 months). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Sep 2025.