Efficacy of Intravenous Melatonin on Mortality in Adult Patients Admitted to the Intensive Care Unit With COVID-19

Phase 2

Completed

• Conditions: Coronavirus Infection; COVID-19; SARS-CoV 2
• Interventions: Drug: Melatonin intravenous; Drug: Placebo intravenous

• Registration Number: NCT04568863
• Lead Sponsor: Pharmamel S.L.

Brief Summary

There is an urgent need to evaluate effective treatments for COVID-19 patients. Melatonin has significant anti-inflammatory and antioxidant properties and it lacks of side-effects. This randomized controlled trial seeks to evaluate the efficacy of intravenous melatonin in reducing mortality in Covid-19 patients in the ICUs.

Detailed Description

ICU COVID-19 patients show high risk of death mainly due to sepsis and respiratory disfunction. Prevention of these critical conditions is mandatory to reduce mortality and to improve patient's outcome.

Melatonin is an endogenous hormone involved not only in circadian rhythm control, but also in the cell protection due to its outstanding anti-inflammatory and antioxidative effects. High doses of melatonin have shown high efficacy against bacterial (sepsis) and viral infections. Melatonin is a safe product that consistently has shown lack of side-effects when it is administered to humans.

SARS-CoV 2 infection may yield severe forms of the disease that require the patients admission to the ICU. These patients may develop an excessive inflammatory response and a burst of free radicals, constituting the major cause of death in these subjects.

Our hypothesis is that high doses of melatonin intravenously administered to COVID-19 ICU patients might reach enough blood levels able to prevent/counteract the developing of sepsis and the production of free radicals, reducing mortality and hospital stay.

Study Timeline

• Study Start: 2020-06-20
• Status Verified: 2020-09
• Study First Submitted: 2020-09-28
• Study First Submitted QC: 2020-09-28
• Study First Posted: 2020-09-29
• Primary Completion: 2020-11-30
• Study Completion: 2020-11-30
• Last Update Submitted: 2021-03-17
• Last Update Posted: 2021-03-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 18

Inclusion Criteria

• Patient, family member or legal guardian has provided written Informed Consent.
• Age ε 18 years.
• Confirmed SARS-CoV-2 infection with compatible symptoms AND a positive RT-PCR.
• Admission to the ICU with acute hypoxemic respiratory failure attributed to SARS-CoV-2 infection.
• ICU length of stay of less than 7 days prior to randomization with or without MV and without signs of improvement in respiratory failure (MURRAY score at randomization greater or equal to the MURRAY score at ICU admission).

Exclusion Criteria

• Participant in a different COVID-19 study in which the study drug is under clinical development and hasn't been previously authorized for commercialization.
• Liver enzymes > 5 times the upper normal range.
• Chronic kidney disease with GFR < 30 mL/min/1.73 m2 (stage 4 or greater) or need for hemodialysis.
• Pregnancy. A pregnancy test will be performed on every woman younger than 55 years of age prior to inclusion.
• Terminal surgical or medical illness.
• Autoimmune disease.
• Any patient condition that can prevent the study procedures to be carried out at the treating physician's judgement.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Melatonin	Melatonin intravenous	(12 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous melatonin every 6 hours. Maximum daily dose 500 mg per day.
Placebo	Placebo intravenous	(6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours.

Primary Outcome Measures

Name	Time	Method
Mortality	one month	Mortality in each study group represented in frequency and time-to-event at day 28 after randomization

Trial Locations

Locations (1)

Hospital Universitario La Paz; 🇪🇸 Madrid, Spain