Oral Bedtime Melatonin in Critically Ill Patients

Study Overview
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Brief Summary
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Oxidative stress is one of the main mechanisms causing harm in severe infection with septic shock, ischemia-reperfusion injury in resuscitated cardiac arrest and ischemic and hemorrhagic stroke. Melatonin is a potent scavenger of the mediators of oxidative stress, oxygen and nitrogen-reactive species, which directly injure cell structures like walls and DNA and thus cause organ dysfunction. In a previous study we have observed that high-dose oral bedtime melatonin (OBM) is associated with improved organ function in severe Covid-19 patients

Detailed Description
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We intend to perform a double-blind randomized, adaptive trial in the 4 indications mentioned above giving 100 mg of OBM or placebo. Interim analyses with pre-specified stopping rules will be perform in each sub-study for specific outcome variables collected at scheduled timelines. Comparative organ dysfunction score (Sequential Organ Failure Evaluation-SOFA) will be done at baseline, 7, 14, and 30 days and mortality evaluated at 30 and 90 days. For the 3 study groups enrolling stroke and resuscitated cardiac arrest patients, the modified Rankin score and the CVC (Glasgow) at 30 and 90 days will be compared.

Official Title
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Oral Bedtime Melatonin in Critically Ill Patients

Conditions
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Septic Shock, Stroke Hemorrhagic, Strokes Thrombotic, Cardiac Arrest

Intervention / Treatment
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* Drug: Oral Bedtime Melatonin
* Drug: Placebo suspension or capsule


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ICU stay >5 days Exclusion Criteria: ominous prognosis
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: double blind randomized
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Septic Shock Standard of Care (SOC)<br>Placebo suspension and capsules | Drug: Placebo suspension or capsule<br>* Indistinguishable suspension or capsule<br>* Other names: Placebo;|
| Active Comparator: Septic shock Oral Bedtime Melatonin (OBM)<br>100 mg suspension or in capsules OBM | Drug: Oral Bedtime Melatonin<br>* 100 mg oral suspension or capsule given at bedtime<br>* Other names: Oral melatonin;|
| Placebo Comparator: Resuscitated Cardiorespiratory Arrest SOC<br>Placebo suspension and capsules | Drug: Placebo suspension or capsule<br>* Indistinguishable suspension or capsule<br>* Other names: Placebo;|
| Active Comparator: Resuscitated Cardiorespiratory Arrest OBM<br>100 mg suspension or in capsules OBM | Drug: Oral Bedtime Melatonin<br>* 100 mg oral suspension or capsule given at bedtime<br>* Other names: Oral melatonin;|
| Placebo Comparator: Ischemic Stroke (SOC)<br>Placebo suspension and capsules | Drug: Placebo suspension or capsule<br>* Indistinguishable suspension or capsule<br>* Other names: Placebo;|
| Active Comparator: Ischemic stroke (OBM)<br>100 mg suspension or in capsules OBM | Drug: Oral Bedtime Melatonin<br>* 100 mg oral suspension or capsule given at bedtime<br>* Other names: Oral melatonin;|
| Placebo Comparator: Hemorraghic stroke (SOC)<br>Placebo suspension and capsules | Drug: Placebo suspension or capsule<br>* Indistinguishable suspension or capsule<br>* Other names: Placebo;|
| Active Comparator: Hemorrhagic stroke (OBM)<br>100 mg suspension or in capsules OBM | Drug: Oral Bedtime Melatonin<br>* 100 mg oral suspension or capsule given at bedtime<br>* Other names: Oral melatonin;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mortality at 90 days | All-cause mortality | Inclusion to 90 days |