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

Sponsor

Pharmamel S.L. (Industry)

Overall Status

Completed

CT.gov ID

NCT04568863

Collaborator

Hospital Universitario La Paz (Other), Instituto de Investigación Hospital Universitario La Paz (Other)

Enrollment

Location

Arms

5.4

Actual Duration (Months)

3.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 SARS-CoV 2 Coronavirus Infection	Drug: Melatonin intravenous Drug: Placebo intravenous	Phase 2

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 Design

Study Type:

Interventional

Actual Enrollment :

18 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

phase II, single-center, double-blind, randomized placebo-controlled trialphase II, single-center, double-blind, randomized placebo-controlled trial

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

A Phase II, Single-center, Double-blind, Randomized Placebo-controlled Trial to Explore the Efficacy and Safety of Intravenous Melatonin in Patients With COVID-19 Admitted to the Intensive Care Unit (MelCOVID Study)

Actual Study Start Date :

Jun 20, 2020

Actual Primary Completion Date :

Nov 30, 2020

Actual Study Completion Date :

Nov 30, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Melatonin (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.	Drug: Melatonin intravenous 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 Comparator: Placebo (6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours.	Drug: Placebo intravenous 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours.

Arm

Intervention/Treatment

Experimental: Melatonin

(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.

Drug: Melatonin intravenous

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 Comparator: Placebo

(6 patients): 7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours.

Drug: Placebo intravenous

7 days of 5 mg per Kg of actual body weight per day of intravenous identically-looking placebo every 6 hours.

Outcome Measures

Primary Outcome Measures

Mortality [one month]
Mortality in each study group represented in frequency and time-to-event at day 28 after randomization

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.