Clinical trial NCT04625985: Metformin Glycinate, Treatment of Patients With COVID-19 and Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2.
Official title: Adaptive Study to Demonstrate Efficacy and Safety of Metformin Glycinate for the Treatment of Hospitalized Patients With Severe Acute Respiratory Syndrome Secondary to SARS-CoV-2. Randomized, Double-Blind, Phase IIIb
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Severe Acute Respiratory Syndrome Coronavirus 2
Keywords: SARS-COV 2
Severe acute respiratory syndrome
Lead sponsor: Laboratorios Silanes S.A. de C.V.
Sponsor class: INDUSTRY
First posted: 2020-11-12
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Experimental: Metformin glycinate 620 mg bid (PO) for 14 days plus standard treatment Control group: placebo bid (PO) for 14 days plus standard treatment

Comparator: Placebo Placebo pill bid (PO) for 14 days plus standard treatment
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to evaluate the efficacy and safety of the metformin glycinate and standard treatment of the hospital in hospitalized patients with Severe Acute Respiratory Syndrome secondary to SARS-CoV2.

Detailed description: After being informed about the study and potential risks, all patients giving written informed consent will undergo a 1 day screening period to determine eligibility for study entry. At day 0, patients who meet the eligibility requirements will be randomized in a double blind manner (participant and investigator) in a 1:1 ratio to metformin glycinate (620 mg, taken orally, twice daily) plus standard treatment or placebo (taken orally, twice daily) plus standard treatment, both for 14 days.

Eligibility criteria: Inclusion Criteria:

1. ≥ 18 years old
2. Ability to understand and the willingness to sign a written informed consent document before any study procedure
3. Coronavirus infection, severe acute respiratory syndrome (SARS-CoV)-2 confirmed by the polymerase chain reaction (PCR) test ≤ 4 days before randomization.
4. Hospitalized
5. Radiographic evidence of pulmonary infiltrates

Exclusion Criteria:

1. Participation in any other clinical trial of an experimental treatment for COVID-19
2. Evidence of multi-organ failure
3. Require mechanical ventilation before randomization
4. Pregnant patients
5. Patients with kidney failure, cancer and among other conditions that due to their treatment and / or baseline condition, affect the distribution, bioavailability and elimination of the studied drug

Primary outcomes:
measure: Viral load
timeFrame: Day 0 to Day 28 or patient discharge day
measure: consciousness level
timeFrame: Day 0 to Day 28 or patient discharge day
measure: temperature
timeFrame: Day 0 to Day 28 or patient discharge day
measure: systolic blood pressure
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Oxigen saturation
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Heart rate
timeFrame: Day 0 to Day 28 or patient discharge day
measure: respiratory rate
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Days of hospitalization
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Days of supplementary oxygen if applies
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Days of supplementary mechanical ventilation
timeFrame: Day 0 to Day 28 or patient discharge day
Secondary outcomes:
measure: Toxicity of study drug assessed by incidence of adverse events (grade 3 or 4)
timeFrame: Day 0 to Day 28 or patient discharge day
measure: Changes in laboratory test results
timeFrame: Day 0 to Day 28 or patient discharge day
Other outcomes:
Locations:
city: Mexico City
country: Mexico
facility: The American British Cowdray Medical Center, I.A.P
Study officials:
affiliation: The American British Cowdray Medical Center. I.A.P.
name: Janet Silvia M Aguirre, MD
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Detaille D, Guigas B, Leverve X, Wiernsperger N, Devos P. Obligatory role of membrane events in the regulatory effect of metformin on the respiratory chain function. Biochem Pharmacol. 2002 Apr 1;63(7):1259-72. doi: 10.1016/s0006-2952(02)00858-4.
citation: Tamura Y, Watada H, Sato F, Kumashiro N, Sakurai Y, Hirose T, Tanaka Y, Kawamori R. Effects of metformin on peripheral insulin sensitivity and intracellular lipid contents in muscle and liver of overweight Japanese subjects. Diabetes Obes Metab. 2008 Sep;10(9):733-8. doi: 10.1111/j.1463-1326.2007.00801.x. Epub 2007 Oct 15.
citation: Standeven KF, Ariens RA, Whitaker P, Ashcroft AE, Weisel JW, Grant PJ. The effect of dimethylbiguanide on thrombin activity, FXIII activation, fibrin polymerization, and fibrin clot formation. Diabetes. 2002 Jan;51(1):189-97. doi: 10.2337/diabetes.51.1.189.
citation: Gonzalez-Ortiz M, Martinez-Abundis E, Robles-Cervantes JA, Ramos-Zavala MG, Barrera-Duran C, Gonzalez-Canudas J. Effect of metformin glycinate on glycated hemoglobin A1C concentration and insulin sensitivity in drug-naive adult patients with type 2 diabetes mellitus. Diabetes Technol Ther. 2012 Dec;14(12):1140-4. doi: 10.1089/dia.2012.0097. Epub 2012 Sep 13.
citation: Jorge González Canudas, COMET GROUP Diabetes Efficacy and Safety of Metformin Glycinate vs. Metformin Hydrochloride in Metabolic Control and Inflammatory Mediators in Type 2 Diabetes Mellitus Patients. Diabetes 2019 Jun; 68(Supplement 1)
citation: Garza-Ocañas L, Tamez-de la O E, Iglesias-Chiesa J, Gonzalez Canudas J, Rivas-Ruiz R: Pharmacokinetics and gastrointestinal tolerability of DMMET 01 (glycinate of metformin): results of a prospective randomized trial in healthy volunteers [abstract]. Diabetes 2009;58(Suppl 1):A533