A Phase 4 interventional study of Melatonin (Circadin ®) and Placebo in Hypoactive Delirium, sponsored by University Hospital, Basel, Switzerland. Recruiting at 1 site in Switzerland. Open to participants aged 55 Years and older. Per ClinicalTrials.gov, last updated 2026-06-11.
Sponsored by University Hospital, Basel, Switzerland · Phase 4, Interventional, and Treatment
Delirium is a neurobehavioural syndrome that frequently develops in the postoperative and/or ICU setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 11-82%. Delirium was first described more than half a century ago in the cardiac surgery population, where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population. This long-term experience with delirium suggests a high socioeconomic liability and has been a focus of many studies. The aforementioned consequences of delirium are observed in all of three subtypes: hypoactive, hyperactive, and mixed. Pharmacological treatment options for hypoactive delirium are lacking. Since patients in hypoactive delirium suffer from disturbed circadian rhythm, the investigators suggest that the administration of melatonin as a promising possibility in these patients to shorten delirium duration and to lower its severity. Previous investigations confirmed loss of melatonin rhythm in patients that had developed delirium thus reasoning the study hypothesis.
In this randomized study, the investigators aim to test the hypothesis that the reinstitution of a normal circadian rhythm by the administration of melatonin compared to placebo after diagnosis of hypoactive delirium, decreases the duration of delirium and reduces the transmission to a form of agitated delirium. The administration might have to be repeated several times to achieve resolution of delirium.
Delirium is a neurobehavioural syndrome that frequently develops in the postoperative and/or ICU setting. The incidence of elderly patients who develop delirium during hospital stay ranges from 10-80%. Delirium was first described more than half a century ago in the cardiac surgery population, where it was already discovered as a state that might be accompanied by serious complications such as prolonged ICU and hospital stay, reduced quality of life and increased mortality. Furthermore, the duration of delirium is associated with worse long-term cognitive function in the general ICU population. This long-term experience with delirium suggests a high socioeconomic liability and has been a focus of many studies. Due to the multifactorial origin of delirium, there are several but no incontestable options for prevention and symptomatic treatment. Overall, delirium represents a high burden not only for the patient and his/her family members, but also for the medical care team that aims to prevent postoperative delirium to avoid serious consequences associated with it.
The aforementioned consequences of delirium are observed in all of three subtypes: hypoactive, hyperactive, and mixed. Many studies have been conducted to prevent and treat hyperactive and mixed delirium. Hypoactive delirium, suggested to be the most frequent form of delirium, is a different case: as it corresponds to a patient that is calm and as such doesn't cause any harm or inconvenience to himself or the caring medical team it also leads to two major problems. First, it is already known that hypoactive delirium is hard to detect. Second, because hypoactive delirious patients are calm or even asleep most of the time this delirium subtype doesn't go along with the same urge to become active in order to prevent harm. Also, pharmacological treatment usually addresses hyperactive and mixed delirium in standard operating procedures, whereas treatment of hypoactive delirium remains supportive. Pharmacological treatment options for hypoactive delirium are lacking. Since patients in hypoactive delirium suffer from disturbed circadian rhythm, investigators suggest that the administration of melatonin is a promising possibility in these patients to shorten delirium duration and to lower its severity. Previous investigations confirmed loss of melatonin rhythm in patients that had developed delirium thus reasoning the study hypothesis. Of note, melatonin is to be investigated for ICU delirium prevention in an Australian study, as the potential of chronotherapy to reduce delirium incidence has been suggested in a recently published article. The administration of dexmedetomidine to treat the disturbed circadian rhythm in hyperactive and mixed delirious ICU patients will be investigated in one of the investigators' current studies, but because of its sedative nature it clearly doesn't represent a treatment option for hypoactive delirium.
The aim of the BOMP-AID trial is to assess the superiority of melatonin to placebo for the treatment of hypoactive delirium in the ICU. The study hypothesis is based on the assumption that melatonin compared to placebo (Lactose monohydrate, cellulose powder, magnesium stearate (Ph. Eur.), mocrocristalline cellulose) administered at night restores a normal circadian rhythm, thus decreasing the duration of delirium and reducing the transmission to a form of agitated delirium.
Investigators would like to recruit 190 patients right after the diagnosis of hypoactive delirium. The administration might have to be repeated several times to achieve resolution of delirium.
After the first administration of melatonin or placebo at 8 p.m. investigators shall follow the standard operating procedure for hypoactive delirium for further treatment of delirium during daytime. In case of previously undiagnosed mixed delirium investigators are forced to follow the standard operating procedure for mixed delirium that includes the administration of haloperidol, quetiapine or trazodone. During the consecutive nightly hours the randomized study substance will be administered again if indicated. The latter will allow investigators to clearly detect the suggested shortening of delirium duration in the cohort where melatonin is being used as treating agent. Any use of drugs to treat forms other than hypoactive will be recorded.
The primary outcome measure is delirium duration in shifts of 8 hours each. Due to difficult diagnosis of hypoactive delirium, the investigators will consider those with an ICDSC score > 2 (subsyndromal delirium) and Richmond Agitation Sedation Scale (RASS) score \< 0 in absence of induced coma as eligible for study inclusion. If patients reveal an ICDSC score > 2 and a RASS score \< 0 a member of the study team will assess the patient according to DSM-V delirium criteria REF] for definite study inclusion. The end of the delirium will be defined as the end of the last shift with an ICDSC > 2 and a RASS score \< 0 that precedes a minimum of two subsequent shifts with an ICDSC \< 3.
Secondary outcomes can be listed as follows:
Since melatonin has no known major side effects evidence of its way of function in the human body strongly suggests high benefit for treatment of hypoactive delirium going along with increased comfort and safety also for critically ill patients. No severe adverse events are expected by its use in delirious patients after careful enrolment following investigators exclusion criteria.
Other outcome measures:
The following outcomes are measured by smartwatches. The smartwatches will be attached half an hour before the administration of the drug (07:30 p.m.) and left attached as long as possible, but at least until 6 a.m. of every day of the study period.
The following smartwatch assessments are based on activity (counts/min):
In addition, wrist/skin temperature (degrees/min) will be registered to assess degree of relaxation (i.e., difference in degrees Celsius per minute between distal skin regions (finger, feet etc) and proximal skin regions (clavicular, sternum etc).
Follow-up:
To assess long-term follow-up of patients who received melatonin and compare it to those who received placebo, we will perform a follow-up at three and twelve months after the prevailing hospital case has been officially closed (discharge date). With this follow-up, we will assess the following information equally at three and twelve months (information either given by the patient or his/her family/contact person):
CRF assessments:
On our electronic case report form, we will document the following information concerning our study participants (sequential order):
933 studies on the registry are indexed under Delirium; 190 are open to participants now.
This study's planned enrollment of 190 is above the median of 112 across 550 interventional studies indexed under Delirium.
Browse Delirium studies →University Hospital, Basel, Switzerland is the lead sponsor of 990 studies on the registry; 189 are open to participants now.
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Participants fulfilling all of the following inclusion criteria are eligible for the study:
Exclusion Criteria:
Participants meeting the following criteria are excluded from the study:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Hypersensitivity
An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Drug: Melatonin (Circadin ®)
Drug: Placebo
4 mg of oral melatonin at 8 p.m. for the length of the duration of the hypoactive delirium
Lactose monohydrate, cellulose powder, magnesium stearate (Ph. Eur.), mocrocristalline cellulose
Also known as: Oral tablet
Duration of hypoactive delirium
Duration of hypoactive delirium in the ICU in 8-hour shifts
Time frame: From study inclusion to delirium resolution, assessed daily until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 28 days
Delirium-free days at 28 days after study inclusion
Duration of Delirium-free days measured in days
Time frame: From study inclusion to ICU discharge, assessed up to 28 days
Death until day 28, day 90, and day 365 from ICU admission
Telephone Survey 28 days, 90 days and 365 days after study inclusion
Time frame: Assessed at 28 days, 90 days, and 365 days after study inclusion
Number of ventilator days
Number of days on mechanical ventilation measured in days
Time frame: From study inclusion until ICU discharge, assessed daily until the date of withdrawal of mechanical ventilation or date of death from any cause, whichever came first, assessed up to 28 days
Length of ICU stay
Length of ICU stay measured in hours
Time frame: From ICU admission to ICU discharge, assessed daily until the date of ICU discharge or date of death from any cause, whichever came first, assessed up to 28 days
Length of hospital stay
Length of hospital stay measured in days
Time frame: From hospital admission to hospital discharge, assessed daily until the date of hospital discharge or date of death from any cause, whichever came first, assessed up to 90 days
Sleep quality
Assessed by the Richards-Campbell Sleep Questionnaire (RCSQ; total score)
Time frame: From study inclusion until study termination, assessed daily until the date of first documented progression (i.e., delirium resolution) or date of death from any cause, whichever came first, assessed up to 28 days
Plan to share: No — Study results will be communicated to patients based on expected speed-up in convalescence from delirious state. During the study ongoing and until publication there will be no access to our data.
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Studies of the drug tested here: Melatonin
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