Glycine by enteral route does not improve major clinical outcomes in severe COVID-19: a randomized clinical pilot trial

Abstract

There is a worrying scarcity of drug options for patients with severe COVID-19. Glycine possesses anti-inflammatory, cytoprotective, endothelium-protective, and platelet-antiaggregant properties, so its use in these patients seems promising. In this open label, controlled clinical trial, inpatients with severe COVID-19 requiring mechanical ventilation randomly received usual care (control group) or usual care plus 0.5 g/kg/day glycine by the enteral route (experimental group). Major outcomes included mortality, time to weaning from mechanical ventilation, total time on mechanical ventilation, and time from study recruitment to death. Secondary outcomes included laboratory tests and serum cytokines. Patients from experimental (n = 33) and control groups (n = 23) did not differ in basal characteristics. There were no differences in mortality (glycine group, 63.6% vs control group, 52.2%, p = 0.60) nor in any other major outcome. Glycine intake was associated with lower fibrinogen levels, either evaluated per week of follow-up (p < 0.05 at weeks 1, 2, and 4) or as weighted mean during the whole hospitalization (608.7 ± 17.7 mg/dl vs control 712.2 ± 25.0 mg/dl, p = 0.001), but did not modify any other laboratory test or cytokine concentration. In summary, in severe COVID-19 glycine was unable to modify major clinical outcomes, serum cytokines or most laboratory tests, but was associated with lower serum fibrinogen concentration.Registration: ClinicalTrials.gov NCT04443673, 23/06/2020.

Figure 1

Flow diagram of patients with severe COVID-19.

Figure 2

Length of hospital stay of patients in control and glycine groups. Gray lines correspond to the time elapsed between patients’ arrival to the emergency room (day 0) and their recruitment into the study. Solid lines represent the study period of survivors (blue lines) and non-survivors (red lines).

Figure 3

Changes in serum fibrinogen in control and glycine groups. Patients receiving glycine (0.5 g/kg/d) showed lower fibrinogen levels evaluated by week of follow-up (A) or by the weighted mean during the whole hospitalization (B). The number of patients appears at the bottom of each bar. *p < 0.05 and ^†p < 0.001.